| TYPE Systematic Review PUBLISHED 12 April 2023 DOI 10.3389/fsurg.2023.1157661 Fully resorbable poly-4-hydroxybutyrate (P4HB) EDITED BY J. Scott Roth, University of Kentucky, United States mesh for soft tissue repair and REVIEWED BY Anita Jacombs, reconstruction: A scoping review Macquarie University Hospital, Australia Shuaishuai Yuan, Corey R. Deeken1, David C. Chen2, Manuel Lopez-Cano3, Qingdao University of Science and Technology, China David P. Martin4 and Amit Badhwar4* 1 *CORRESPONDENCE Covalent Bio, LLC, St. Louis, MO, United States, 2Section of Minimally Invasive Surgery, David Geffen School of Medicine at University of California, Los Angeles, Santa Monica, CA, United States, 3Hospital Amit Badhwar Universitario Vall d’Hebrón, Universidad Autónoma de Barcelona, Barcelona, Spain, 4Becton, Dickinson amit.badhwar@bd.com and Company, Warwick, RI, United States SPECIALTY SECTION This article was submitted to Visceral Surgery, a section of the journal Frontiers in Surgery Background: Poly-4-hydroxybutyrate (P4HB) is a fully resorbable, biologically- produced polymer with a strength and flexibility comparable to permanent RECEIVED 02 February 2023 ACCEPTED 22 March 2023 synthetic polymers. The objective was to identify/summarize all peer-reviewed PUBLISHED 12 April 2023 publications involving P4HB mesh. CITATION Methods: A scoping review was conducted within PubMed and included articles Deeken CR, Chen DC, Lopez-Cano M, published through October 2022. Martin DP and Badhwar A (2023) Fully Results: A total of n = 79 studies were identified (n = 12 in vitro/bench; n = 14 resorbable poly-4-hydroxybutyrate (P4HB) preclinical; n = 6 commentaries; n = 50 clinical). Of the clinical studies, n = 40 mesh for soft tissue repair and reconstruction: reported results applicable to hernia and n = 10 to plastic/reconstructive surgery A scoping review. Front. Surg. 10:1157661. and involved patients of all Centers for Disease Control (CDC) wound classes doi: 10.3389/fsurg.2023.1157661 and Ventral Hernia Working Group (VHWG) grades. COPYRIGHT Conclusion: P4HB mesh provides long-term hernia repair strength and exhibits © 2023 Deeken, Chen, López-Cano, Martin and promising clinical outcomes beyond its resorption period. Future studies should Badhwar. This is an open-access article include randomized controlled trials comparing P4HB to other biomaterials, as distributed under the terms of the Creative Commons Attribution License (CC BY). The use, well as optimal patient selection, operative technique, long-term outcomes, distribution or reproduction in other forums is minimization of potential mesh-related complications, and potential permitted, provided the original author(s) and contraindications/complications for P4HB in hernia/abdominal wall reconstruction. the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. KEYWORDS No use, distribution or reproduction is permitted which does not comply with these hernia recurrence, P4HB, Phasix Mesh, poly-4-hydroxybutyrate (P4HB), resorbable, surgical terms. site infection (SSI) 1. Introduction The development of a unique, fully resorbable, biologically-produced, thermoplastic polyester called poly-4-hydroxybutyrate (P4HB) was first reported in 2003 for implantable medical device applications (TephaFLEX®, Tepha Inc., Lexington, Massachusetts) (1). While the chemical synthesis of P4HB is possible (2–4), the molecular weight needed for practical applications as an implantable fiber or mesh can presently only be achieved by fermentation, and there are currently no chemically synthesized P4HB-based products used in commercial medical products or devices. Rather, P4HB is typically produced through a biologic recombinant fermentation process using Escherichia coli K12, a microorganism widely utilized in the biopharmaceutical industry to develop other products for human use (1, 5–7). Thus, P4HB is free of the residual metal catalysts that are common in chemically-derived polymers (1, 7). The resulting P4HB is extracted from Frontiers in Surgery 01 frontiersin.org Deeken et al. 10.3389/fsurg.2023.1157661 the fermented cells, purified and processed into fibers using hernia, and hiatal/paraesophageal hernia) (27–31). The objective established plastics processing techniques (1, 5, 8). of the current study was to review the results of all peer-reviewed P4HB is a strong and flexible material, with a tensile strength studies involving P4HB mesh, guided by the following research comparable to permanent synthetic polymers such as questions: polypropylene and ultrahigh molecular weight polyethylene and can be stretched up to 10× its initial length prior to failure (1, 6, (1) How has P4HB mesh been evaluated to date (i.e., benchtop, 7). P4HB can also be tailored to achieve a wide range of physical preclinical, and clinical peer-reviewed studies)? and mechanical properties as desired for various applications (1). (2) What is the clinical role of P4HB mesh in hernia repair, P4HB has a long-term degradation profile of 12–18 months abdominal wall surgery, and plastic/reconstructive surgery? (5, 9) and degrades into 4HB fragments through bulk hydrolysis, (3) What are the knowledge gaps and opportunities for future as well as surface erosion (5, 7). With a half-life of approximately research for P4HB? 30 min, 4HB degradation products are quickly metabolized through the Krebs cycle, and eliminated as carbon dioxide and water (1, 5, 7). The gradual resorption process results in a steady decline in mechanical strength for a P4HB mesh as the load is 2. Methods progressively transferred back to the repaired tissue (1, 6). This is a major benefit compared to many other resorbable polymers A scoping review of the published literature was conducted that degrade rapidly through bulk hydrolysis, resulting in a steep according to the PRISMA-ScR Guidelines (Preferred Reporting decline in mechanical strength before the wound has had time to Items for Systematic Reviews and Meta-Analyses—extension for sufficiently remodel (1, 7). Scoping Reviews) (32). A search string with Boolean operators The United States Food and Drug Administration (FDA) was utilized to retrieve results within the PubMed database, cleared monofilament P4HB suture and monofilament P4HB along with a hand search of references from eligible articles, surgical mesh for human use in 2007, followed by regulatory reviews on the topic that were not identified in the literature clearance in Europe in 2009 (5). P4HB has subsequently been search, and personal reference collections. Search terms included: utilized to develop a variety of commercially-available devices, “poly-4-hydroxybutyrate” OR “4-hydroxybutyrate mesh” OR including: sutures for tissue approximation (MonoMax® “P4HB” OR “Phasix” + “hernia” and included articles published Suture, Aesculap AG, Tuttlingen, Germany), scaffolds to through October 2022. Inclusion criteria included: all peer- support tendon and ligament repair (BioFiberTM Scaffold, reviewed papers involving P4HB mesh, that were published in Tornier, Inc., Edina, MN), biomaterials for plastic and the English language, and which could be obtained as a full-text. reconstructive surgery (GalaFLEX® Scaffold, Galatea Surgical, Abstracts, posters, slide presentations, and Letters to the Editor Inc., Lexington, MA), and meshes for hernia repair (PhasixTM were excluded, as well as articles in which 4HB was combined Mesh, Becton, Dickinson, and Company, Franklin Lakes, NJ) with other monomers to form a copolymer; P4HB was used as a (1, 5–7). Currently, P4HB mesh is available in two coating material rather than as a mesh construct; or those configurations for hernia repair: as a bare, macroporous mesh articles in which it was determined to be a polymer other than (PhasixTM Mesh) or combined with a resorbable hydrogel layer P4HB after review of the full-text. (PhasixTM ST Mesh). The hydrogel layer, comprised of sodium Outcomes of interest were recorded in a tabular format. Studies hyaluronate (HA), carboxymethylcellulose (CMC), and were grouped according to category (i.e., bench, preclinical, clinical, polyethylene glycol (PEG) (9), serves as a barrier that commentary). Publication date, mesh type, summary of results, minimizes tissue adherence of the bowels to the underlying and citation were recorded for all study categories. For bench mesh by separating the abdominal viscera from the P4HB studies, the type of study and its objective, the technique used, mesh structure (10). The uncoated side of the mesh is porous and the results were collected. For preclinical studies in animals, to allow tissue ingrowth the abdominal wall. The hydrogel is the species used, the surgical technique, the mesh evaluated, and fully resorbed in approximately 30 days (10). The addition of the implantation time were recorded. For clinical studies, the this hydrogel barrier layer to P4HB mesh provides a fully number of patients in the trial, as well as details of the surgical resorbable, barrier mesh option appropriate for intraperitoneal technique and study design were recorded. Additionally, follow- placement (11, 12). up period and clinical outcomes such as quality of life metrics In the last decade, P4HB mesh has been clinically studied in the and rate of hernia recurrence, surgical site infection (SSI), and scientific literature across several surgical specialties (7). In the area reoperation were captured and tabulated. Centers for Disease of plastic and reconstructive surgery, P4HB mesh has been used Control (CDC) wound classification (33) and Ventral Hernia primarily in breast surgery (13–21), with some early work in Working Group (VHWG) grades (34, 35) were likewise reported. rhytidectomy (16, 22). P4HB mesh has also been evaluated as a Studies were classified as “restricted” if the study design limited potential biomaterial for the repair of pelvic organ prolapse in the inclusion of patients with specific CDC wound classification urogynecological surgery (23–26). The majority of data and or VHWG grades based on either the original (31) or modified clinical research using P4HB mesh has focused on general (32) grading systems. Similarly, studies were classified as surgery applications, particularly in the area of hernia repair (i.e., “unrestricted” if the study design permitted the inclusion of all ventral/incisional hernia, incisional hernia prophylaxis, inguinal CDC wound classes and VHWG grades. Frontiers in Surgery 02 frontiersin.org Deeken et al. 10.3389/fsurg.2023.1157661 3. Results A subset of the identified publications (n = 12) involved in vitro studies, benchtop testing, cadaver studies, review articles, and ex vivo Following the PRISMA-ScR schematic (Figure 1), a total of studies that were broadly categorized as “bench studies” as shown in n = 79 full-text, peer-reviewed publications were identified that Figure 2, and Table 1 (5–8, 22, 36–42). Several major themes were involved P4HB mesh and were published in the English language. identified within these studies, namely a correlation between the The articles were subdivided into type of study—bench (n = 12), mechanical strength of P4HB meshes and their remaining preclinical (n = 14), commentaries (n = 6), and clinical (n = 50) in molecular weight during degradation studies, as well as the cellular Figure 2 and Table 1. The clinical studies were further subdivided response to P4HB mesh constructs and their degradation into plastic and reconstructive surgery (n = 10) and general surgery products. In an in vitro degradation test performed by Martin (n = 40). The general surgery population was then divided into et al. (6), P4HB mesh exhibited a significant reduction in incisional hernia prophylaxis (n = 2) and hernia repair based on mechanical strength and molecular weight over time, which type: inguinal hernia (n = 2), hiatal/paraesophageal hernia (n = 5), correlated with the integrity of the individual fibers comprising the and ventral/incisional hernia (n = 31). Lastly, all ventral/incisional mesh. They found that when changes to the structure of the mesh hernias were stratified, when possible, by CDC wound class, could first be appreciated visually through scanning electron VHWG grade, and/or follow-up period. All published studies are microscopy, the mechanical strength and molecular weight of the summarized in Table 1, including commentaries comprised of P4HB mesh had already been reduced by approximately 90% (6). plastic and reconstructive surgery (16, 17, 87), general surgery (86, Martin et al., utilized this mechanical strength and molecular 88), and urogynecology (25). Table 2 summarizes the clinical weight data to construct a standard curve that can be used to outcomes associated with P4HB mesh in incisional hernia predict the ball burst strength of P4HB mesh when molecular prophylaxis, inguinal hernia repair, and hiatal/paraesophageal weight is known. Care must be used, however, before applying hernia repair. Table 3 summarizes the clinical outcomes associated such a correlation to different forms of the polymer, as the degree with ventral/incisional hernia repair. Studies without specified of orientation imparted during processing affects the susceptibility follow-up time, case reports, and protocols without outcomes data of P4HB to enzymatic degradation and surface erosion in vivo. were not included in Tables 3 or 4, but are reported in Table 1 A number of bench studies also investigated the degradation for completeness. products of P4HB mesh (i.e., 4HB monomer) using murine bone FIGURE 1 PRISMA-ScR diagram—preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews. Frontiers in Surgery 03 frontiersin.org Deeken et al. 10.3389/fsurg.2023.1157661 FIGURE 2 Flowchart depicting depth and breadth of studies that have evaluated P4HB mesh. *n = 3 articles with both Bench and Preclinical components. DIEP, deep inferior epigastric perforator flap. marrow-derived macrophages (36, 37, 42). These studies found that Table 1. Several outcomes were identified within these preclinical the degradation products are not cytotoxic, and in fact, may help studies. First, P4HB meshes provided a durable and long-lasting promote bacterial clearance by macrophages through an hernia repair with mechanical strength of the mesh-repaired site upregulation of antimicrobial peptides (AMPs) (36, 37, 42). The equal to or greater than the native porcine abdominal wall in degradation products have also been shown to influence the studies of 24-, 52- and 72-week duration (i.e., 6-, 12- and 18- cellular expression of macrophage phenotypes of murine bone month duration) (6, 43, 44). Second, P4HB meshes activated marrow-derived macrophages (37) and potentially provoke a macrophages from a pro-inflammatory phenotype (M1) to a pro- unique polarization state in human peripheral blood-derived remodeling phenotype (M2) earlier in the postoperative period macrophages (41). Cellular response to P4HB meshes was than all of the other meshes evaluated (i.e., BardTM Mesh, favorable compared to polypropylene meshes, including higher TIGR®, Bio-A®, and StratticeTM meshes). Finally, in numerous collagen I : III ratio, as well as improved cellular attachment and studies involving subcutaneous dorsal implantation of P4HB proliferation (38, 40). Additionally, despite greater surface area mesh with deliberate bacterial contamination, monofilament relative to polypropylene mesh, P4HB meshes were not associated P4HB meshes exhibited significantly reduced bacterial with greater bacterial adhesion or biofilm formation (39). colonization relative to other mesh types (36, 45, 89). Fourteen publications identified by this scoping review The majority of the identified publications (n = 50/79; 63%) involved preclinical studies in a variety of animal models and involved clinical studies describing the use of P4HB mesh in species, including pigs, rats, rabbits, sheep, mice, and vervets plastic and reconstructive surgery (n = 10) (13–15, 18–21, 56, 61, (Figure 2, and Table 1) (6, 23, 24, 26, 36, 37, 43–49, 89). Three 64) or general surgery applications (n = 40) (11, 12, 27–31, 50–55, of these studies (n = 3) contained both a benchtop component 57–60, 62, 63, 65–85) as shown in Figure 2, and Table 1. In the and a preclinical component (6, 36, 37). These studies are area of plastic and reconstructive surgery, P4HB meshes have been reported in both categories and included in Figure 2, and utilized primarily in cosmetic breast applications (21) including Frontiers in Surgery 04 frontiersin.org TABLE 1 Study design parameters and outcomes associated with all published studies involving P4HB mesh. Author (Year) Type of Study Technique Meshes Summary of Results Ref Deeken et al. Evaluated Bench Studies Frontiers in Surgery Martin (2013) Bench Accelerated degradation PhasixTM Mesh Significant reduction in molecular weight and mechanical strength over time; correlation between strength (6) Bard Mesh and fiber integrity Williams (2013) Review Tissue repair and regeneration P4HB Review of FDA cleared devices comprised of P4HB; presentation of mechanical properties and other (5) characteristics of P4HB; discussion of devices currently under development and related patents Angelos (2014) Cadaver Rhytidectomy (facelift) P4HB Superficial musculoaponeurotic system (SMAS) tissue reinforced with P4HB demonstrated significantly (22) improved mechanical properties compared to SMAS without reinforcement. Williams (2016) Review Plastic & Reconstructive Surgery GalaFLEX (P4HB) P4HB fibers are associated with high initial mechanical strength, encourage tissue ingrowth, and offer a (7) long resorption period, leading to a durable repair. Potential applications in rhytidectomy and breast reconstruction are discussed. Pineda Molina In vitro Murine bone marrow-derived macrophages Phasix monomer (4HB) 4HB monomer was not cytotoxic, exhibited increased expression of cathelicidin LL-37 [i.e., an (36) (2019, AMP) antimicrobial peptide (AMP), cramp], and induced transcriptional activation of the AMP β-defensin-4 in murine bone marrow-derived macrophages; 4HB promoted bacterial resistance through upregulation of antimicrobial peptides (AMPs); 4HB could be used in drug delivery or to functionalize the surface of biomaterials to protect against bacterial contamination. Pineda Molina In vitro Murine bone marrow-derived macrophages Phasix monomer (4HB) PhasixTM Mesh degradation products (4HB) significantly decreased cellular expression of the pan (37) (2019, M1/M2) (naïve or pre-activated) macrophage marker F4/80 and significantly increased cellular expression of the M2 macrophage markers Fizzz1 and Arginase1. Trapani (2020) Ex vivo model Mesh embedded in human abdominal fascia PhasixTM Mesh After 54 days of culture, both meshes displayed disorganized collagen. PhasixTM Mesh exhibited a higher (38) tissue Polypropylene collagen I : III ratio than polypropylene mesh and the control group (no mesh), with favorable mechanical Control (no mesh) properties. 05 Verhorstert (2020) In vitro Bacterial adherence and biofilm formation P4HB mesh Despite greater surface area of P4HB meshes compared to polypropylene meshes, P4HB did not exhibit (39) Polypropylene greater bacterial adhesion or biofilm formation. Diedrich (2021) In vitro Fibroblast attachment and proliferation P4HB mesh P4HB exhibited improved cellular attachment and proliferation and significantly greater collagen (40) Polypropylee deposition at 28 days; Knit design parameters could potentially influence/optimize cellular behavior. Mora-Navarro In vitro Human peripheral blood-derived GalaFLEX (P4HB) Human peripheral blood-derived macrophages exposed to P4HB mesh in vitro, co-expressed genes (41) (2021) macrophages Prolene associated with inflammatory, non-inflammatory, and pathogen response phenotypes, suggesting that Vicryl exposure to P4HB may provoke a unique polarization state. Mersilene TIGR SERI AlloDerm Pineda Molina In vitro Murine bone marrow-derived macrophages Phasix monomer (4HB) The results of this study identified the molecular mechanism responsible for transcriptional activation of (42) (2021) (naïve or pre-activated) the antimicrobial peptide cathelicidin LL-37 (Cramp). Upregulation of the Cramp gene occurred via modulation of GPR109A, a G-protein coupled receptor, and was independent of histone deacetylase (HDAC) activity. Singh (2021) Bench Low-temperature spinning process P4HB filaments Development of wet-spinning process to produce P4HB fibers with a variety of morphologies, mechanical (8) properties, and melting properties; A number of polymer concentrations, bath temperatures, and spin ratios were evaluated. Author (Year) Species Surgical Technique Meshes Implantation Time Summary of Results Ref. Evaluated Preclinical Studies Martin (2013) Pig Repair of a full fascial anterior abdominal PhasixTM Mesh 0, 8, 16, 32, 48, 72 At 72 weeks post-implantation, PhasixTM Mesh-repaired sites demonstrated (6) wall defect weeks significantly reduced molecular weight of the P4HB polymer, while maintaining (continued) frontiersin.org 10.3389/fsurg.2023.1157661 TABLE 1 Continued Author (Year) Type of Study Technique Meshes Summary of Results Ref Evaluated Deeken et al. comparable mechanical strength as the native abdominal wall, suggesting that PhasixTM Mesh provides a durable repair. Frontiers in Surgery Deeken (2013) Pig Repair of bilateral abdominal wall defect PhasixTM Mesh 6, 12, 26, 52 weeks The burst strength of porcine abdominal wall tissue repaired with PhasixTM Mesh (43) remained stable, with no loss of strength throughout the implantation period. Significant material resorption was documented via significant reduction in molecular weight over time. The burst strength of the PhasixTM Mesh-repaired sites remained significantly higher than the native abdominal wall, suggesting successful augmentation of the repair over the 52-week implantation period, despite ongoing resorption. A favorable mild-moderate granulation tissue/neovascularization and mild inflammatory response were also observed. Scott (2016) Pig Bilateral repair of abdominal wall defects Retromuscular: 12 and 24 weeks The burst strengths of porcine abdominal wall tissues repaired PhasixTM ST, (44) PhasixTM Mesh Strattice Ventralight ST, and PhasixTM meshes remained stable, with no loss of strength Intraperitoneal: throughout the 24- week implantation period. All mesh-repaired sites exhibited burst PhasixTM ST strengths significantly greater than the native abdominal wall, suggesting successful Ventralight ST augmentation of the repair sites over the 24-week implantation period. In contrast, the Strattice-repaired sites exhibited a significant decrease in burst strength in the first 12 weeks. Although Strattice-repaired sites exhibited burst strengths significantly higher than the NAW, PhasixTM-repaired sites were significantly stronger than Strattice-repaired sites at both 12 and 24 weeks postimplantation. Stoikes (2017) Rat SubQ PhasixTM Mesh 2, 4, 8, 12, 16, 24 PhasixTM Mesh exhibited greater mechanical strength, along with lower abscess (45) Rabbit SubQ w/bacteria Bio-A weeks scores, bacterial colonization, and inflammation compared to Bio-A. 7 days 06 Lake (2019) Rabbit Bilateral subQ pockets inoculated with PhasixTM Mesh 7 days Three out of four of the hybrid meshes evaluated exhibited significant bacterial (44) MRSA Synecor colonization at 7 days postimplantation/inoculation. In contrast, PhasixTM Mesh Zenapro exhibited a favorable response to bacterial inoculation, with abscess scores of zero, Ovitex Permanent negative pocket swabs, and zero cases of positive bacterial colonization. Ovitex Resorbable Miserez (2019) Review of 11 studies: rats, Various PhasixTM Mesh Various Systematic review of the physicochemical characteristics and biomechanical, (46) sheep, rabbits, pigs, Bio-A histological, and clinical outcomes associated with resorbable meshes in experimental vervets TIGR Matrix preclinical studies. Pineda Molina Rat Bilateral partial thickness abdominal defect PhasixTM Mesh 3, 7, 14, 21 & 35 Both PhasixTM and polypropylene meshes were associated with increased expression (36) (2019, AMP) AND Polypropylene days of the AMP cramp (i.e., cathelicidin LL-37), which was the highest in the PhasixTM SubQ dorsal mesh implantation with mesh group. bacterial contamination After deliberate bacterial contamination, polypropylene meshes exhibited significantly greater S. aureus colonies compared to PhasixTM Mesh, suggesting that the 4HB monomer resists bacterial contamination. Pineda Molina Rat Bilateral partial thickness abdominal defect Bard Mesh 3, 7, 14, 21 & 35 PhasixTM Mesh activated macrophages from a pro-inflammatory phenotype (M1) to (37) (2019, M1/M2) TIGR days a pro-remodeling phenotype (M2) earlier in the postoperative period than other Bio-A meshes evaluated and demonstrated favorable tissue remodeling characteristics at 35 PhasixTM Mesh days postimplantation. Strattice In comparison, the response produced by Bard Mesh, TIGR, Bio-A, and Strattice were all dominated by the M1 pro-inflammatory macrophage phenotype. Deeken (2020) Pig Ventral hernia repair: 4 and 8 cm unclosed PhasixTM ST 48 and 72 weeks PhasixTM ST Mesh remained intact at 48 weeks, but degraded into fragments by 72 (47) & 8 cm closed defects weeks. Mature collagen/fibrovascular tissue was observed around and within the mesh pores. Similar mechanics, degradation, and histological results were observed regardless of defect size or closure technique. Pascual (2020) Rabbit Partial abdominal wall defects 3, 6, 12, 18 months (48) (continued) frontiersin.org 10.3389/fsurg.2023.1157661 TABLE 1 Continued Author (Year) Type of Study Technique Meshes Summary of Results Ref Evaluated Deeken et al. PhasixTM Mesh PhasixTM Mesh was associated with fewer macrophages than Protexa at the later time Protexa points, but many of the other outcomes were similar between meshes (collagen Frontiers in Surgery ingrowth, implant area, mechanics). Diedrich (2021) Sheep Implantation in the posterior vaginal wall P4HB 60 and 180 days P4HB mesh was associated with increased M2/M1 ratio, evidence of densely packed (23) Polypropylene collagen fibers, and low myofibroblast differentiation, suggesting favorable tissue response and similar load-bearing compared to polypropylene mesh. O-Shaughnessy Rabbit SubQ and peri-vaginal PhasixTM Mesh 3 and 9 months PhasixTM Mesh and permanent polypropylene mesh exhibited similar mechanical (24) (2021) Polypropylene strength and histological results at both time points, suggesting that Phasix Mesh may be a feasible alternative for pelvic organ prolapse repair. Pascual (2021) Rabbit Mesh implantation on the intact parietal PhasixTM ST 3, 7, 14 and 90 days At 90 days postimplantation, PhasixTM Meshes were associated with greater M2 (49) peritoneum Symbotex macrophage expression and fewer macrophages overall compared to Symbotex. The TM Optilene neoperitoneum associated with Phasix Mesh was significantly thicker than that of the other meshes and was comprised of mature, organized tissue. Verhorstert (2022) Mouse Subcutaneous implantation of mesh in P4HB 4, 9, 60 days Host tissue response, clearance of bacteria, and adverse events were similar for P4HB (26) infection model with intentional bacterial Polypropylene and polypropylene meshes despite the larger surface area associated with P4HB inoculation mesh. Author (Year) Type of Study Surgical Technique Meshes Number of Summary of Results Ref Evaluated Patients Clinical Studies Adams (2017) Prospective, Single center Primary mastopexy with soft tissue GalaFLEX (P4HB) 11 This study showed promising results when GalaFlex (P4HB) was used to reinforce (13) reinforcement the lower pole of the breast in n = 11 consecutive patients. The lower pole stretched 07 5% over 12 months. Buell (2017) Retrospective review Complex abdominal wall reconstruction Strattice: n = 42 73 PhasixTM Mesh exhibited significantly fewer complications and recurrences, with a (50) with primary fascial closure & mesh overlay PhasixTM: n = 31 significant cost savings relative to Strattice. Wormer (2017) Retrospective review Deep inferior epigastric perforator (DIEP) PhasixTM n = 160 319 PhasixTM Mesh may improve cosmesis (reduce postoperative bulge) following DIEP (14) flap breast reconstruction with onlay mesh No mesh n = 159 reconstruction, with similar donor site complications as repairs completed without mesh reinforcement. Adams (2018) Prospective, multicenter Elective mastopexy and reduction GalaFLEX (P4HB) 62 GalaFLEX successfully corrected ptosis and maintained that correction at 1 year after (18) mammaplasty implantation in 89.7% of cases. Plymale (2018) Prospective pilot study Ventral and incisional hernia repair; Rives– PhasixTM Mesh 31 At 24-months follow-up, there were no hernia recurrences or infections, and quality (51) Stoppa approach with retrorectus mesh of life was significantly improved over baseline; 19.4% of patients experienced an placement adverse event (e.g., seroma, wound necrosis, and wound dehiscence). Roth (2018) Prospective, multicenter Retrorectus or onlay VIHR PhasixTM Mesh 121 At 18-months follow-up, patients at high risk for postoperative complications (52) experienced low rates of hernia recurrence (9%), SSI (9%), seroma (6%), reoperation (8%), and adverse events (9%) when repaired with PhasixTM Mesh. van Rooijen (2018) Prospective, multicenter VHWG Grade 3 midline incisional hernia PhasixTM Mesh 85 Protocol for upcoming clinical trial; no results presented; Primary outcome = surgical (53) repair using (retrorectus or onlay) site occurrence (SSO) through 3 months postimplantation Secondary outcomes = recurrence, infection, and quality of life through 24 months postimplantation Kniepeiss (2019) Randomized control trial Prophylactic onlay mesh placement to PhasixTM Mesh 194 Protocol for upcoming clinical trial; no results presented; Primary outcome = (54) prevent incisional hernia repair after liver No mesh incisional hernia at 12 months post-implantation Secondary outcome = incisional transplantation hernia at 24 months post-implantation and rate of mesh-related complications (i.e., hematoma, seroma, pain, wound dehiscence, infection, mesh removal) Messa (2019) Retrospective review Complex VHR PhasixTM Mesh 70 24-months after complex VHR, PhasixTM Mesh demonstrated significant (55) improvement in quality-of-life metrics, low hernia recurrence rates (5.7%), and favorable clinical outcomes (low rates of seroma and wound dehiscence and no cases of mesh infection or excision). frontiersin.org 10.3389/fsurg.2023.1157661 (continued) TABLE 1 Continued Author (Year) Type of Study Technique Meshes Summary of Results Ref Evaluated Deeken et al. Nair (2019) Retrospective review Complex breast revision GalaFLEX (P4HB) 5 GalaFLEX demonstrated favorable aesthetic outcomes when used to prevent sagging (56) of the lower pole in breast reconstruction procedures, with improvement in Baker Frontiers in Surgery Grade Contraction scores. Abdelmoaty (2020) Retrospective review of Laparoscopic repair of paraesophageal PhasixTM ST 50 This study demonstrates the safety and efficacy of PhasixTM ST Mesh for crural (57) prospective database hernia reinforcement at the hiatus over the short-term (median: 12 months follow-up); No major complications were reported (mesh infection or erosion); Recurrence rate (8%) and reoperation rate (0%) were low. Aiolfi (2020) Retrospective single- Laparoscopic posterior cruroplasty for hiatal No mesh (n = 102) 141 Low rates of complications (4.2%) and recurrences (2.1%) were observed, along with (58) center review hernia repair PhasixTM ST (n = 39) improved quality of life metrics, but the results were not subdivided into mesh-based repairs versus suture repair without mesh reinforcement. Aldohayan (2020) Prospective pilot study Laparoscopic TAPP inguinal hernia repair PhasixTM Mesh 15 PhasixTM Mesh performed well in this pilot study, with no hernia recurrences (0%) (28) and very limited chronic pain in inguinal hernias repaired via laparoscopic TAPP technique. Calobrace (2020) Retrospective review Popcorn capsulorrhaphy in revision GalaFLEX (P4HB) 149 The technique of popcorn capsulorrhaphy can improve control and stability of the (19) aesthetic breast surgery pocket in aesthetic breast surgery. The use of a mesh such as GalaFLEX may reduce complications and revisions. Levy (2020) Retrospective review Tissue expander-based breast reconstruction PhasixTM (n = 62) 169 PhasixTM Mesh was associated with significantly shorter drain duration compared to (15) after mastectomy AlloMax (107) AlloMax, with comparable incidence of infection, necrosis, seroma, and reoperation. Mellia (2020) Review of previous Ventral hernia repair PhasixTM Mesh 453 Systematic review of the literature showed low rates of SSI (6.8%), reoperation (59) literature (10.7%) and hernia recurrence (9.1%); Onlay repairs were associated with significantly higher rate of recurrences compared to sublay. Pakula (2020) Retrospective review Complex ventral hernia repair with PhasixTM Mesh 20 At a mean follow-up of 21.1 months following implantation of PhasixTM Mesh, low (60) 08 retromuscular mesh rate of recurrence (0%), SSI (10%), and seroma (10%) were observed in this cohort of high-risk patients. Panici Tonucci Single-center Laparoscopic repair of hiatal hernia PhasixTM ST 73 At a median follow-up of 17 months, PhasixTM ST Mesh was shown to be safe and (29) (2020) observational cohort study reinforced with mesh effective for reinforcing crural repairs at the hiatus (3.2% recurrence and 0% mesh- related complications, with significantly improved quality of life metrics and no reoperations required). Rehnke (2020) Retrospective review Breast reconstruction with 3-D mesh and Lotus scaffold: comprised of 22 At a mean follow-up of 19 months, adipose tissue was observed around the Lotus (61) autologous fat grafting PhasixTM Mesh, TIGR Matrix, scaffold. No capsule formation, oil cysts, or calcification was observed, and all or SERI patients were satisfied with the cosmetic outcome (i.e., size and shape of reconstructed breast). Rognoni (2020) Observational, Primary ventral or incisional hernia repair PhasixTM Mesh PhasixTM ST 75 PhasixTM and PhasixTM ST Mesh demonstrated promising outcomes with low rates (62) prospective, multi-center of recurrences (8.0%) and complications (1.3% infected mesh removal; 4.0% SSI with study intervention, 6.7% seroma with intervention, and 5.3% reoperation) and significantly improved quality of life metrics. van Rooijen (2020) Prospective, multi-center VHWG Grade 3 midline incisional hernia PhasixTM Mesh 84 At short-term follow-up of 3 months, encouraging results were reported when (63) single-arm study repair (potentially contaminated) PhasixTM Mesh was used to repair potentially contaminated incisional hernias (0% hernia recurrence, 13% SSI). Yu (2020) Retrospective review Bilateral free flap breast reconstruction PhasixTM n = 40 66 Though more expensive than polypropylene or primary repair, PhasixTM Mesh (64) Polypropylene n = 20 successfully reinforced the abdominal wall, leading to significantly fewer Primary closure n = 6 complications compared to polypropylene mesh (PhasixTM Mesh: 0% seroma, 0% wound dehiscence, 0% reoperation, and 0% hernia) (Polypropylene mesh: 10% seroma, 20% wound dehiscence, 10% reoperation, and 10% hernia) Aldohayan (2021) Retrospective review Laparoscopic ventral/incisional hernia PhasixTM ST 26 At a mean follow-up of 28 months following implantation of PhasixTM ST Mesh, 0% (65) repair hernia recurrence and 0% wound infection were reported, with pain levels consistently decreasing over time. (continued) frontiersin.org 10.3389/fsurg.2023.1157661 TABLE 1 Continued Author (Year) Type of Study Technique Meshes Summary of Results Ref Evaluated Deeken et al. Buell (2021) Retrospective cohort study Complex abdominal wall reconstruction PhasixTM n = 31 73 At 5 year follow-up, PhasixTM Mesh exhibited significantly improved clinical (30) Strattice n = 42 outcomes (complications, recurrences, infections) and significant cost-savings Frontiers in Surgery compared to porcine dermal matrices (Strattice). Bueno-Lledo (2021, Retrospective review Replacement of infected mesh with PhasixTM Mesh 71 PhasixTM Mesh was associated with 7% recurrence and 1.4% infection when utilized (66) Abd) PhasixTM using a one-stage (n = 30) or two- in single-stage management of chronic mesh infection and may represent a better stage (n = 41) surgical approach option than two-stage approach. Bueno-Lledo (2021, Retrospective review Single-stage treatment of chronic mesh PhasixTM Mesh 30 Clinical outcomes were promising nearly three years after implantation of PhasixTM (67) Bio) infection with mesh removal and PhasixTM Mesh to replace infected mesh (3.3% recurrence, 3.3% infection). mesh implantation Charleux-Muller Retrospective cohort, Incisional hernia repair in contaminated PhasixTM n = 90 215 At an average follow-up of 11.7 months, PhasixTM and PhasixTM ST repairs in (68) (2021, Slowly) multicenter surgical field PhasixTM ST n = 103 contaminated fields exhibited an overall recurrence rate of 12.4% and SSI of 22.3% Charleux-Muller Retrospective analysis Potentially contaminated hernia repair Biologic mesh n = 52 94 In a cost-effectiveness model, PhasixTM Mesh was shown to be more clinically (69) (2021, Cost) PhasixTM n = 42 effective (fewer serious complications) and less costly than biologic mesh in VHWG Grade 3 hernia repairs. Christopher (2021, Retrospective analysis Ventral hernia repair PhasixTM Mesh 71 Despite nearly one-third of cases in contaminated settings, PhasixTM Mesh exhibited (70) An Eval) a reasonable recurrence rate (12.7%) with significant improvement in quality-of-life metrics over time. Christopher (2021, Retrospective review Complex ventral hernia repair PhasixTM Mesh 51 At a median follow-up of 20.8 months after PhasixTM Mesh implantation during (71) Onlay) complex VHR, 5.9% patients experienced hernia recurrence and 15.7% experienced an SSI. Christopher (2021, Retrospective cohort study Ventral hernia repair in CDC wound class PhasixTM Mesh 60 At a median follow-up of 24.2 months postimplantation in contaminated settings, (72) Resorb) II–IV (VHWG Grade 3–4) PhasixTM Mesh was associated with 8.3% recurrence, 16.7% SSI, and significantly 09 improved quality of life, suggesting an acceptable safety profile in a complex and high-risk population. Claessen (2021) Retrospective study Open single-stage complex abdominal wall PhasixTM n = 40 70 In this complex, comorbid population, patients were at high risk of complications (73) reconstruction Bio-A n = 30 regardless of mesh type. TM At a median follow-up of 35 months, Phasix Mesh was associated with 10% hernia recurrence rate, similar to that of Bio-A (10%, median follow-up: 11 months). Bio-A meshes were salvaged more frequently (100%) than PhasixTM Meshes (58.8%) after direct contact with SSI. The long-term durability of Bio-A remains unknown, and further studies are warranted. Faulkner (2021) Retrospective review Prophylactic mesh augmentation PhasixTM Mesh 50 At a median follow-up of 2.2 years, PhasixTM Mesh exhibited promising results when (27) used to prevent incisional hernia formation (4% seroma, 4% SSI, 20% hernia development); no mesh infections observed; longer-term studies are justified Lambrecht (2021) Case report Conservative treatment of a patient with a PhasixTM Mesh 1 In this case report, an infected PhasixTM Mesh was successfully treated in a (74) heavily infected Phasix mesh conservative manner without mesh excision, demonstrating some of the potential benefits associated with this material. Levy (2021) Prospective evaluation Complex abdominal wall reconstruction PhasixTM Mesh 105 At 36 months follow-up (mean) after complex abdominal wall reconstruction with (75) PhasixTM Mesh, favorable recurrence (17%) infection (5%), and seroma (6%) rates were observed. Roth (2021) Prospective, multicenter Retrorectus or onlay VIHR PhasixTM Mesh 121 At 36-months follow-up, 0% of patients developed late mesh-related complications (76) study requiring removal, while 9.3% reported SSI and 17.9% exhibited hernia recurrence. van Driel (2021) Retrospective, single-arm Inguinal or ventral hernia or to replace PhasixTM Mesh 47 At short-term follow-up (mean 140 days; median 48 days), mesh excision was (11) multicenter infected synthetic mesh PhasixTM ST required in only n = 1 case despite contaminated or dirty conditions at the time of mesh implantation. Conservative management and minor reoperations were required, and further research is warranted. (continued) frontiersin.org 10.3389/fsurg.2023.1157661 TABLE 1 Continued Author (Year) Type of Study Technique Meshes Summary of Results Ref Deeken et al. Evaluated van Rooijen (2021) Prospective multicenter Ventral hernia repair PhasixTM Mesh 84 Reasonable recurrence (8%) and reoperation (15.5%) rates were observed 24 months (77) Frontiers in Surgery clinical trial after implantation of PhasixTM Mesh in VHWG Grade 3 patients. No significant improvement in pain or quality of life metrics were observed. Vauclair (2021) Prospective evaluation Incisional hernia repair with sublay or PhasixTM Mesh 29 At 1 year following implantation of PhasixTM Mesh in potentially contaminated (78) intraperitoneal mesh placement incisional hernias, there were no instances of mesh infection (0%) and reasonable rates of hernia recurrence (10.3%). Aiolfi (2022) Retrospective, single Laparoscopic paraesophageal hernia repair PhasixTM ST 68 At a median follow-up of 27 months, PhasixTM ST was associated with 8.8% hernia (79) center study with Toupet fundoplication recurrence, 0% mesh-related complications, 0% reoperation, and significant improvement in quality-of-life metrics over baseline. Hope (2022) Prospective, multicenter Laparoscopic or robotic PhasixTM ST 120 At 24 months postimplantation, PhasixTM ST Mesh was associated with low rates of (12) VIHR SSO and mesh-related complications and improved quality-of-life metrics, but recurrence rates were high at 31.7%. Further analysis indicated that recurrence rates were higher in large defects (≥7.1 cm2), indicating that PhasixTM ST Mesh may be better suited for small defects until additional studies can further investigate outcomes in laparoscopic IPOM of large defects. Konstantinidis Retrospective cohort study Laparoscopic hiatal hernia repair with 360° PhasixTM ST 30 At a median follow-up of 14 months following repair of large, complicated hiatal (80) (2022) Nissen fundoplication hernias, PhasixTM ST Mesh was associated with 0% hernia recurrence and 0% mesh- related complications. Layer (2022) Retrospective, multicenter Abdominal wall repair with onlay, PhasixTM Mesh 108 At a mean follow-up of 41 months following abdominal wall repair with PhasixTM (81) retromuscular, or intraperitoneal mesh PhasixTM ST Mesh or PhasixTM ST Mesh in high-risk, contaminated wounds, recurrence rates (22.2%) were lower than biologic mesh in similar populations and comparable to 10 synthetic mesh in the general population. Lima (2022) Retrospective, single Abdominal wall repair with mesh PhasixTM Mesh 51 At a median follow up of 3.5 months (105 days) following abdominal wall repair with (82) center study PhasixTM ST PhasixTM Mesh, hernia recurrence was low at 4.1%, and SSI at 30 days was 13.7% Mallucci (2022) Observational study Aesthetic breast surgery GalaFLEX (P4HB) 100 GalaFLEX was utilized in n = 100 aesthetic breast surgeries in an observational case (20) series. Photographic analysis showed that the lower pole position was stable over a median follow-up period of 14 months, Many secondary defects such as inferior malposition and symmastia were corrected through the use of this biomaterial. Othman (2022) Retrospective, single Abdominal wall reconstruction with onlay PhasixTM Mesh 88 (n = 44/mesh Higher rates of recurrence, complications, and cost were associated with (83) center study resorbable mesh or intraperitoneal biologic Biologic Mesh type) intraperitoneal biologic mesh implantation compared to onlay resorbable synthetic mesh (XenMatrix or Permacol) mesh (PhasixTM Mesh). Roth (2022) Prospective, multicenter Retrorectus or onlay VIHR PhasixTM 121 At 60-months follow-up, comorbid patients undergoing VIHR with PhasixTM Mesh (31) experienced 10.1% SSI, 14.9% reoperation, 22.0% recurrence, and improved quality of life compared to baseline. Schecter (2022) Retrospective, single Single-stage abdominal wall reconstruction P4HB 34 At a mean follow-up of 37 months following single-stage abdominal wall (84) center study in contaminated or dirty/infected wounds reconstruction in contaminated (CDC Class III) or dirty/infected (CDC Class IV) wounds, P4HB mesh was associated with low incidence of hernia recurrence (6%), seroma with intervention (12%), and surgical site infection (9%), with no instances of mesh-related adverse events, mesh infection, or mesh explantation. Sigalove (2022) Retrospective, study Two-stage, expander-implant, prepectoral GalaFLEX-AlloDerm n = 135 patients (n The addition of a P4HB component (GalaFLEX) to the AlloDerm repair resulted in (21) breast reconstruction AlloDerm = 250 breasts) comparable postoperative complications as repairs completed with AlloDerm alone. n = 128 patients (n Future studies are warranted to evaluate this biomaterial over a long-term period. = 249 breasts) Talwar (2022) Retrospective, single Retrorectus or onlay VIHR PhasixTM 51 At a median follow-up of 62.3 months, patients undergoing VIHR with PhasixTM (85) center study Mesh experienced 20% recurrence, 3.9% SSI, 11.8% reoperation, and significantly improved quality of life at all time periods evaluated frontiersin.org 10.3389/fsurg.2023.1157661 Deeken et al. 10.3389/fsurg.2023.1157661 mastopexy/reduction mammaplasty (18, 19), prevention of bulge at (16) (17) (86) (87) (25) (88) Ref the donor site on the abdominal wall (14, 64), support of the lower pole (13, 20, 56), tissue expander-based reconstruction (15), and 3-D mesh breast reconstruction with autologous fat grafting (61). P4HB meshes have been utilized extensively in general surgery for a wide variety of hernia repair and abdominal wall reconstruction applications (11, 12, 27–31, 50–55, 57–60, 62, 63, 65–85). A small number of studies (n = 2 in each group) evaluated P4HB mesh for incisional hernia prophylaxis (27, 54) and inguinal hernia repair (Table 1, and Table 2) (11, 28). Commentary on Rehnke et al. (61)—discussion of the difficulties in ensuring adequate oxygen delivery to support fat graft survival and prevent Commentary on O-Shaughnessy et al. (24)—recommends P4HB mesh as an alternative to permanent mesh for pelvic organ prolapse repair Several studies (n = 5) also explored the use of P4HB mesh in hiatal/paraesophageal hernia repair (Table 1, and Table 2) (29, 57, 58, 79, 80). These studies reported favorable clinical outcomes, including low hernia recurrence rates (range: 0%–8%) and no surgical site infections (SSI), mesh-related complications, or reoperations with follow-up periods of at least 1 year. Most of the general surgery studies identified by this literature review (n = 31/40; 78%) utilized P4HB mesh in the repair of ventral/incisional hernias, primarily at the midline (Table 1 and Consensus statements regarding the use of biosynthetic absorbable mesh in VHWG Grades 2–3 hernias Table 3) (12, 30, 31, 50–53, 55, 59, 60, 62, 63, 65–78, 81–85). Commentary on Deeken et al. (47)—recommends more clinical trials, including RCT and registries Primary fascial closure was planned in all cases, with definitive repair as the goal. In contaminated cases, bridging repair with A review of the concept of an “internal bra” for reconstructive and aesthetic breast surgery A review of the clinical use of P4HB mesh in both facial and breast surgery applications P4HB was performed as an initial stage operation, with a future, planned definitive repair. Twenty-five (n = 25) studies utilized retrorectus/retromuscular, n = 11 underlay, n = 18 onlay, and n = 2 inlay mesh repair, with many studies incorporating a variety of surgical approaches and tissue planes. These studies documented a wide range of follow-up periods, including short-term (<2 years), intermediate (2–3 years), and long-term (>3 years) studies (Table 3), with P4HB meshes implanted in several different tissue planes, through a variety of surgical techniques. It should be noted that clinical outcomes were evaluated in patients along the entire continuum of Centers for Disease Control (CDC) wound classes (33) and Ventral Hernia Working Group (VHWG) grades (34, 35), ranging from clean cases at low risk of calcification or formation of cysts postoperative complications to contaminated/dirty cases at high risk of postoperative complications (Table 4). Systematic reviews (59), commentaries (86), and clinical studies of CDC Class I Summary of Results (clean) cases only (51, 65) comprised a small number of articles, with the majority of the identified clinical studies describing complex cases with elevated CDC wound class or comorbidities placing patients at high risk of postoperative complications (n = 13) (12, 30, 31, 50, 52, 55, 60, 62, 71, 75, 76, 83, 85) or “off- label” use of P4HB mesh to repair ventral/incisional hernias in potentially contaminated or contaminated fields (n = 15) (11, 53, 63, 66–70, 72–74, 77, 78, 81, 82, 84). After a thorough evaluation of the clinical studies identified by this scoping review, several major themes emerged, namely: (1) P4HB mesh provides long- term strength at the repair site, leading to acceptable rates of recurrence as compared to higher-risk cohorts and those repaired with non-synthetic biomaterials (30, 31, 66, 70, 75, 76); (2) Morales-Conde (2022) Table 1 Continued P4HB mesh performs favorably in contaminated settings where Rostaminia (2021) Commentaries Berrevoet (2020) Haddock (2020) permanent synthetic mesh use may be higher risk or Adams (2016) Author (Year) Baxter (2016) contraindicated, resulting in low incidence of surgical site infection (SSI) (70, 76, 90); and (3) P4HB mesh represents an alternative for ventral/incisional hernia repair relative to biologic Frontiers in Surgery 11 frontiersin.org Deeken et al. 10.3389/fsurg.2023.1157661 TABLE 2 Clinical outcomes associated with P4HB mesh in incisional hernia prophylaxis, inguinal hernia repair, and hiatal/paraesophageal hernia repair. Author (Year) Type of Study Surgical Technique Meshes Number Follow-Up Summary of Results Ref Evaluated of (time) Patients Incisional Hernia Prophylaxis Kniepeiss (2019) Randomized controlled Prophylactic onlay mesh placement to PhasixTM Mesh 194 1, 3, 6, 12, 18, Protocol for planned (54) trial prevent incisional hernia repair after liver No mesh 24 months clinical trial; transplant No results presented Faulkner (2021) Retrospective review Prophylactic mesh augmentation PhasixTM Mesh 50 2.2 years Seroma = 4% (27) SSI = 4% Mesh infection = 0% Hernia development = 20% Inguinal Hernia Repair Aldohayan (2020) Prospective pilot study Laparoscopic TAPP inguinal hernia repair PhasixTM Mesh 15 1 week Hernia recurrence = 0% (28) 1, 3, 6, 12, 24 Pain = 8.3% at 12 months months (0% at 24 months) van Driel (2021) Retrospective, Single-arm Inguinal/ventral hernia or to replace PhasixTM Mesh 47 48 days Hernia recurrence (11) Multicenter infected synthetic mesh PhasixTM ST (overall): 12.8% SSI (overall): 23.4% Hiatal/Paraesophageal Hernia Repair Abdelmoaty Retrospective review of Laparoscopic repair of paraesophageal PhasixTM ST 50 12 months Hernia recurrence = 8% (57) (2020) prospective database hernia SSI = 0% Aiolfi (2020) Retrospective single- Laparoscopic posterior cruroplasty for No mesh n = 102 141 21 months Hernia recurrence = 2.1% (58) center review hiatal hernia repair PhasixTM ST n = Pain = decreased 39 significantly over time Panici Tonucci Single-center Laparoscopic repair of hiatal hernia with PhasixTM ST 73 17 months Hernia recurrence = 3.2% (29) (2020) observational cohort study mesh Aiolfi (2022) Retrospective, single Laparoscopic paraesophageal hernia repair PhasixTM ST 68 27 months Hernia recurrence = 8.8% (79) center study with Toupet fundoplication Mesh-related complications = 0% Reoperation = 0% QoL metrics = improved over baseline Konstantinidis Retrospective cohort Laparoscopic hiatal hernia repair with 360° PhasixTM ST 30 14 months Hernia recurrence = 0% (80) (2022) study Nissen fundoplication Mesh-related complications = 0% meshes and when permanent synthetic mesh complications are postimplantation in studies involving CDC wound classes II–III taken into consideration (30, 69). (92) and 14% SSI at a median follow-up of 24 months in studies P4HB mesh provides a long-term resorption profile with an involving CDC wound classes II–IV (93)]. initial mechanical strength similar to permanent synthetic mesh Studies demonstrated a cost savings associated with P4HB (6). However, once the P4HB polymer has been fully resorbed, the mesh relative to biological tissue-based materials such as porcine mesh contributes negligible strength to the overall repair, allowing dermal matrix (StratticeTM, Allergen Aesthetics, Madison, NJ) for the potential for hernia recurrence. The current scoping review (30, 69). In a study by Buell et al., P4HB mesh exhibited documented comparable recurrence rates for P4HB mesh at 3 and improved clinical outcomes including hernia recurrence and was 5 years postimplantation [6.6%–17.9% (66, 70, 75, 76) and 12.9%– associated with a cost savings of $10,595 compared to porcine 22.0% (30, 31), respectively] as permanent synthetic mesh at 5 dermal matrix (StratticeTM, p = 0.005) (30). In a cost-effectiveness years postimplantation (12.7%) (91) in study populations involving model, Charleux-Muller et al., showed that P4HB mesh repairs a variety CDC wound classes and VHWG grades. are associated with fewer serious complications (21% vs. 33%) The clinical literature also revealed that P4HB mesh performs and are less costly than biological tissue-derived materials (cost favorably in the setting of contamination, evidenced by low rates savings of $42,883) in VHWG Grade 3 hernia repairs (69). of SSI at 3 years postimplantation. Similar rates were reported in studies involving all CDC wound classes and VHWG grades (i.e., 5%–7%) (70, 90). These outcomes are supported by the bench 4. Discussion and preclinical studies in which P4HB mesh degradation products were shown to promote bacterial resistance and tissue Poly-4-hydroxybutyrate (P4HB) mesh has been studied for more remodeling through upregulation of AMPs and influence over than a decade, including a broad collection of in vitro, preclinical, macrophage phenotype (36, 37). In CDC class I (clean) wounds, and clinical studies. To date, this biomaterial has been utilized in P4HB was associated with 9.3% SSI, a rate higher than seen in patients along the entire spectrum of CDC wound classes and mesh based cohorts (76). However, permanent synthetic meshes VHWG grades, ranging from patients with clean wounds at low have been associated with higher rates of SSI in studies involving risk of postoperative complications to patients with contaminated/ CDC wound classes II–IV [e.g., 7%–19% SSI at 30 days dirty wounds at high risk of postoperative complications. Short- Frontiers in Surgery 12 frontiersin.org TABLE 3 Clinical outcomes associated with P4HB mesh in ventral/incisional hernia repair; categorized by follow-up time. Author (Year) Type of Study Patients Meshes Surgical Technique Follow-Up Recurrence (%) SSI (%) Re-operation Quality of Ref Deeken et al. Evaluated (months) (%) Life Short-Term Studies (<2 years follow-up) Frontiers in Surgery Roth (2018) Prospective, 121 PhasixTM Retrorectus or onlay VIHR 18 9% 9% 8% Improved over (52) multicenter baseline Pakula (2020) Retrospective 20 PhasixTM Complex VIHR with retromuscular mesh placement 21.1 0% 10% NR Improved over (60) baseline van Rooijen (2020) Prospective, 84 PhasixTM Retrorectus or onlay VHR 3 0% 13.1% NR NR (63) multicenter Rognoni (2020) Prospective, 75 PhasixTM Primary VIHR ≥18 8% 4% 5.3% Improved over (62) multicenter PhasixTM ST baseline Charleux-Muller Retrospective cohort, 215 PhasixTM n = 90 Incisional hernia repair in contaminated surgical field 11.7 14.1% 22.3% NR NR (68) (2021, Slowly) multicenter PhasixTM ST n = 103 Christopher (2021, Retrospective 51 PhasixTM Complex VIHR 20 (median) 5.9% 15.7% 7.8% Improved over (71) Onlay) baseline Claessen (2021) Retrospective 70 PhasixTM: n = 40 Open, single-stage complex abdominal wall 20 (median) PhasixTM: 10% PhasixTM: 25% PhasixTM: 25% NR (73) Bio-A: n = 30 reconstruction Bio-A: 10% Bio-A: 23.3% Bio-A: 13.3% Lima (2022) Retrospective 51 PhasixTM Abdominal wall repair 3.5 (median) 4.1% 13.7% (at 30 NR NR (82) days) Vauclair (2021) Prospective 29 PhasixTM Incisional hernia repair with sublay mesh 12 10.3% 0% NR NR (78) 13 Intermediate-Term Studies (2–3 years follow-up) Plymale (2018) Pilot study 31 PhasixTM Retrorectus VIHR 24 0% NR NR Improved over (51) baseline Messa (2019) Retrospective 70 PhasixTM Retrorectus or onlay VIHR 24 5.7% 8% 11% Improved over (55) baseline Aldohayan (2021) Retrospective, single 26 PhasixTM ST Laparoscopic VIHR 28 0% 0% NR NR (65) center Bueno-Lledo (2021) Retrospective 30 PhasixTM One-stage treatment of chronic mesh infection with 34.5 3.3% 3.3% NR NR (67) mesh removal and implantation of new mesh Bueno-Lledo (2021) Retrospective review 71 PhasixTM: n = 30 Replacement of infected mesh with PhasixTM using a 36 PhasixTM: 6.6% PhasixTM: 3.3% PhasixTM: 0% NR (66) Synthetic: n = 41 one-stage approach or synthetic mesh in a two-stage Synthetic: 7.2% Synthetic: 9.8% Synthetic: 7.3% approach Christopher (2021, Retrospective 60 PhasixTM VIHR in CDC wound class II–IV (VHWG grade 3 & 24.2 (median) 8.3% 16.7% 15% Improved over (72) Resorb) 4) baseline Levy (2021) Prospective 105 PhasixTM Complex abdominal wall reconstruction with onlay 36 17% 5% 15% NR (75) mesh Roth (2021) Prospective, 121 PhasixTM Retrorectus or onlay VIHR 36 17.9% 9.3% 11.6% Improved over (76) multicenter baseline van Rooijen (2021) Prospective, 84 PhasixTM Retrorectus or onlay VHR 24 11% 13.1% 15.5% Improved over (77) multicenter baseline Hope (2022) Prospective, 120 PhasixTM ST Laparoscopic or Robotic VIHR 24 31.7% 0% 18.3% Improved over (12) multicenter baseline (continued) frontiersin.org 10.3389/fsurg.2023.1157661 Deeken et al. 10.3389/fsurg.2023.1157661 Ref term, intermediate, and long-term clinical studies have been (83) (30) (70) (81) (31) (84) (85) performed, including implantation in many different tissue planes, Improved over Improved over Improved over using a wide variety of surgical techniques. This comprehensive Quality of Life literature review yielded 79 peer-reviewed, published studies baseline baseline baseline evaluating P4HB mesh in a wide variety of bench, preclinical, and NR NR NR NR clinical study designs. Importantly, 40 clinical studies provide a StratticeTM: 14.0% Re-operation current understanding of the performance of P4HB mesh in PhasixTM: 10.0% hernia repair and abdominal wall reconstruction. In the scope of 14.9% 11.8% 8.5% (%) NR NR NR hernia repair, P4HB remains a novel material. These early studies suggest that P4HB mesh provides strength at the repair site beyond its resorption profile, leading to reasonable rates of PhasixTM: 18.2% PhasixTM: 12.9% Biologics: 25.6% recurrence especially in settings where use of permanent synthetic StratticeTM: (p = 0.45) SSI (%) 31.0% 24.1% 10.1% mesh is avoided or contraindicated. P4HB performed favorably in 3.9% 7% 9% the setting of contamination, resulting in low incidence of surgical site infection (SSI). Recent long-term studies, including Roth (31) and Talwar (85), also demonstrated improvement in long-term Recurrence (%) Biologics: 22.7% (p StratticeTM: 38.1% PhasixTM: 12.9% PhasixTM: 4.5% quality of life metrics. < 0.026) 12.7% 22.2% 22.0% 20% Preclinical studies demonstrate long-term resorption of P4HB 6% over a period of approximately 12–18 months, during which the mesh loses all of its mechanical strength (6, 43, 44, 47). The clinical studies identified in this literature review provided insight 24.5 (median) 43.1 (median) 62.3 (median) Follow-Up (months) into the performance of P4HB in a variety of patient populations 60 41 60 37 and clinical scenarios. Once the P4HB polymer has been fully resorbed, the mesh no longer contributes to the mechanical strength of the repair. This property has important implications in hernia repair, stressing the importance of operative technique and Abdominal wall repair with onlay, retromuscular, or primary fascial closure to achieve durable long-term results. Two Single-stage abdominal wall reconstruction in studies utilized P4HB mesh in the inlay position, serving primarily Complex abdominal wall reconstruction Complex abdominal wall reconstruction Surgical Technique as tissue coverage and to prevent fascial retraction as a salvage or contaminated or dirty/infected wounds staged operation for future definitive repair. In all clinical studies where definitive hernia repair was desired, the defect was closed Retrorectus or onlay VIHR Retrorectus or onlay VIHR with mesh either in the underlay, retrorectus/retromuscular plane, or onlay position. These findings compliment the premise that the intraperitoneal mesh long-term resorbable matrix confers mechanical strength during the vulnerable phases of wound healing, shifting the curve to favorable mature scar formation with the potential for a durable VIHR repair beyond the resorption profile of the P4HB. Several clinical studies warrant in-depth discussion. First, in a PhasixTM (n = 44) PhasixTM (n = 31) Biologics (n = 44) study restricted to patients with CDC class I (clean) wounds at Evaluated StratticeTM (n = PhasixTM Mesh Meshes PhasixTM ST high risk of developing postoperative complications (i.e., VHWG PhasixTM PhasixTM PhasixTM grade ≥2) Roth et al. evaluated clinical outcomes including SSI, P4HB hernia recurrence, and quality of life over a period of 5 years (31, 42) 52, 76). Incidence of SSI remained consistent over time with 9.0%, Patients 9.3%, and 10.1% SSI reported at 18, 36, and 60 months, 108 121 88 73 71 34 51 respectively (31, 52, 76). Throughout the follow-up period, recurrence rates rose from 9% at 18 months to 17.9% at 36 Retrospective, single Retrospective, single Retrospective, single Type of Study Long-Term Studies (>3 years follow-up) months, and ultimately, 22% at 60 months postimplantation (31, 52, 76). However, these reported recurrence rates are interesting Retrospective, Retrospective Retrospective Prospective, multicenter multicenter given that at this long-term time point, it is expected that there is center center center no residual material and can be viewed as acceptable given a patient population at high risk of postoperative complications such TABLE 3 Continued as recurrence (i.e., VHWG grade ≥2). In this context, P4HB is a Christopher (2021) Author (Year) Othman (2022) Schecter (2022) viable option, especially where avoidance of a permanent synthetic Talwar (2022) Layer (2022) Buell (2021) Roth (2022) is desired based upon patient factors, operative conditions, and both patient and surgeon preference. Kanters et al. have demonstrated that the risk of hernia recurrence increases Frontiers in Surgery 14 frontiersin.org Deeken et al. 10.3389/fsurg.2023.1157661 TABLE 4 CDC wound class and ventral hernia working group (VHWG) grade associated with clinical studies involving P4HB mesh in ventral/incisional hernia repair. Author (Year) Number of Patients CDC Wound Class VHWG Grade†,‡ Ref Unrestricted Restricted Unrestricted Restricted Buell (2017) 73 X X (50) Plymale (2018) 31 X (Class I & II) X (51) Roth (2018) 121 X (Class I) X (Grade ≥2)† (52) Messa (2019) 70 X X (55) Pakula (2020) 20 X X (60) Rognoni (2020) 75 X X (Grade 2 & 3)† (62) van Rooijen (2020) 84 X X (Grade 3)† (63) Aldohayan (2021) 26 X X (65) Buell (2021) 73 X X (30) Bueno-Lledo (2021, Abd) 71 X (Class IV) X (66) Bueno-Lledo (2021, Bio) 30 X (Class IV) X (67) Charleux-Muller (2021, Slowly) 215 X (Class ≥2) X (Grade ≥2)‡ (68) Charleux-Muller (2021, Cost) 94 X X (Grade 3)‡ (69) Christopher (2021, An Eval) 71 X X (70) Christopher (2021, Onlay) 51 X X (71) Christopher (2021, Resorb) 60 X (Class ≥2) X (72) Claessen (2021) 70 X X (73) Levy (2021) 105 X X (75) Roth (2021) 121 X (Class I) X (Grade ≥2)† (76) van Rooijen (2021) 84 X X (Grade 3)† (77) Vauclair (2021) 29 X X (78) Hope (2022) 120 X (Class I) X (Grade ≥2)† (12) Layer (2022) 108 X (Class ≥2) X (Grade 3 & 4)† (81) Lima (2022) 51 X X (82) Othman (2022) 88 X X (83) Roth (2022) 121 X (Class I) X (Grade ≥2)† (31) Schecter (2022) 34 X (Class ≥3) X (84) Talwar (2022) 51 X X (85) Unrestricted = “all comers” design; Restricted = defined by protocol inclusion criteria. † VHWG grade (original scale). ‡ VHWG grade (modified scale). significantly in patient populations with elevated VHWG grade (35). W.L. Gore & Associates, Inc., Flagstaff, AZ) implanted in clean- In this context, long-term recurrence rates for P4HB mesh are contaminated and contaminated wounds in a population with comparable to those reported for permanent synthetic meshes at 5 multiple comorbidities predictive of postoperative complications and 10 years [12.7% (91) and 32% (94), respectively]. (95). In the RICH trial, Itani et al. reported rates of recurrence of In a study involving patients across all CDC wound classes and 28% and SSI of 35% for a biological tissue-derived material all VHWG grades, Buell et al. evaluated long-term clinical (StratticeTM) in patients with CDC class II, III, or IV wounds (96). outcomes associated with P4HB mesh compared to a porcine Finally, when P4HB mesh was utilized to replace infected mesh dermal matrix (StratticeTM) (30). At 60-months postimplantation, in a single-stage approach, Bueno-Lledo et al., reported a recurrence StratticeTM was associated with approximately 3× greater rate of 6.6% and SSI of 3.3% (mean follow-up of 36.5 months) (66). incidence of recurrence (38.1%) and SSI (31.0%) compared to They compared these results to a second cohort in which permanent P4HB (12.9% recurrence, p = 0.017; 12.9% SSI, p = 0.071) (30). synthetic mesh was used to replace infected mesh in a two-stage Hernia recurrence and SSI rates associated with P4HB were approach. The permanent synthetic mesh cohort exhibited a comparable to the published literature. recurrence rate comparable to P4HB mesh (7.2%; p = 0.101), but In another study, P4HB mesh was utilized “off-label” in 3× greater incidence of SSI (9.8%, p = 0.002) (66). contaminated hernia repairs, Christopher et al. reported hernia Previous studies have shown that the risk of surgical site recurrence of 8.3% and SSI of 16.7% at 24 months occurrences (SSOs) such as SSI increases with increasing CDC postimplantation in a patient population with CDC wound class ≥2 wound class (35). However, the current literature review showed and VHWG grade ≥3 hernia repairs (72). These represent that P4HB mesh is associated with relatively low rates of SSI favorable results compared to similar studies involving other types compared to other resorbable materials or biological tissue-derived of hernia repair materials. In the COBRA trial, Rosen et al. matrices, including in patient populations with elevated CDC reported comparable SSI (18%) and 2× higher recurrence rates wound class. These outcomes are supported by bench and (17%) for another fully resorbable polymer mesh material (Bio-A®, preclinical studies in which P4HB mesh degradation products Frontiers in Surgery 15 frontiersin.org Deeken et al. 10.3389/fsurg.2023.1157661 were shown to promote bacterial resistance and tissue remodeling and abdominal wall surgery, including hernia prophylaxis, through upregulation of AMPs and influence over macrophage inguinal hernia, and as an alternative to permanent synthetic phenotype (36, 37). Based on the current literature, P4HB mesh in routine hernia repair. provides a viable option for repair in this challenging patient population at higher risk for infection and recurrence. As a scoping review, the current study is not without limitations. Data availability statement First, the quality of the studies included in this review was not formally assessed as would be completed in a systematic review or The original contributions presented in the study are included meta-analysis. Nor, were the potential biases of any of the included in the article/Supplementary Material, further inquiries can be studies discussed. The majority of the studies in this review are directed to the corresponding author. observational with the corresponding limitations. Roth et al. provides the longest-term follow-up to 60 months, but is a single- arm, observational trial with follow-up capturing only 44.6% of the cohort (31). Due to the limited follow-up, the actual recurrence and Author contributions SSI rates would be expected to be higher, and the risk of bias is Study conception and design: AB, CD. Data collection: AB, CD. greater than data derived from a randomized controlled trial. This Data analysis and interpretation: AB, DC, CD, ML, DM. Drafting is an inherent limitation and challenge of large-scale clinical of manuscript: AB, DC, CD, ML, DM. Critical revision: AB, DC, research and provides insight to guide future research. CD, ML, DM. Final approval of version submitted for Several knowledge gaps in the existing literature were identified publication: AB, DC, CD, ML, DM. All authors contributed to by the current scoping review, generating a number of research the article and approved the submitted version. questions to be addressed. Future studies should continue to evaluate P4HB mesh for a variety of clinical applications in the field of hernia repair. Inguinal hernia repair and incisional hernia prophylaxis are particularly promising areas of research Funding that warrant additional studies with long-term follow-up and comprehensive evaluation of clinical outcomes. Future studies This project was sponsored by Becton, Dickinson and are also needed to compare outcomes associated with P4HB Company (BD) of Warwick, Rhode Island (USA). CD is the mesh to those of permanent synthetic meshes, particularly in owner of Covalent Bio, LLC, which received consulting fees from non-complicated cases (i.e., CDC class I, VHWG grade 1). BD for this project, as well as other, unrelated projects. DM and Permanent synthetic meshes have traditionally been utilized in AB are employees of BD. DC and ML are consultants for BD. these cases, and data is currently lacking for P4HB mesh in this patient population. The operative technique and mesh position are key to obtaining a durable repair with a completely Conflict of interest resorbable mesh. Dedicated studies and a systematic review are needed to clearly define the optimal surgery, tissue plane, and This project was sponsored by Becton, Dickinson and Company the significance of fascial closure. One of the advantages of a (BD) of Warwick, Rhode Island (USA). CD is the owner of Covalent fully resorbable material such as P4HB is to address increasing Bio, LLC, which received consulting fees from BD for this project, as public sentiment and medicolegal implications regarding the use well as other, unrelated projects. DM and AB are employees of BD. of permanent prosthetics in surgery and provide durable DC and ML are consultants for BD. CD reports consulting fees from alternatives. The ongoing desire to identify the optimal C.R. Bard, Inc./Davol/Becton Dickinson (BD) during the conduct of prosthetic in hernia repair remains one of the central research the study. DC also reports consulting fees from C.R. Bard, Inc./ themes in the field of hernia and abdominal wall reconstruction. Davol/Becton Dickinson (BD), Johnson & Johnson, Medtronic, Finally, randomized controlled trials (RCT) evaluating P4HB SurgiMatrix, Tissium, Surgical Innovation Associates, Americas mesh against other biomaterials are absent in the scientific Hernia Society Quality Collaborative, Colorado Therapeutics, literature and are needed to properly delineate the appropriate TelaBio, Osteogenics, Polynovo, MedSkin Solutions, and Aran and ideal role of P4HB in hernia repair. Biomedical outside the submitted work. In addition, CD is the owner of Covalent Bio, LLC and holds the following issued patents: 2009293001, 2334257, 2,334,257UK, 602009046407.8, 5. Conclusions 2,334,257FR, 16/043,849 and 2,737,542. DC reports consulting fees from Becton Dickinson (BD) during the conduct of this study. The use of P4HB is safe and effective in hernia repair, but more ML reports consulting fees from Becton Dickinson (BD) during research is needed. Repair with P4HB provides strength beyond the the conduct of this study. DM reports employment by Becton scope of its resorption profile with promising results in the context Dickinson (BD) during the conduct of this study, as well as of contamination and demonstrates a role where the avoidance of a outside of the current work. AB reports employment by Becton permanent mesh prosthesis is desired. Future studies are warranted Dickinson (BD) during the conduct of this study, as well as to evaluate the appropriate and optimal role for P4HB in hernia outside of the current work. Frontiers in Surgery 16 frontiersin.org Deeken et al. 10.3389/fsurg.2023.1157661 Publisher’s note organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or All claims expressed in this article are solely those of the claim that may be made by its manufacturer, is not guaranteed authors and do not necessarily represent those of their affiliated or endorsed by the publisher. References 1. Martin D, Williams S. Medical applications of poly-4-hydroxybutyrate: a strong 22. Angelos PC, Brennan TE, Toriumi DM. Biomechanical properties of flexible absorbable biomaterial. Biochem Engr J. (2003) 16:97–105. doi: 10.1089/ superficial musculoaponeurotic system tissue with vs without reinforcement with 107632703322066660 poly-4-hydroxybutyric acid absorbable mesh. JAMA Facial Plast Surg. (2014) 16 (3):199–205. doi: 10.1001/jamafacial.2013.2738 2. Shen Y, Zhao Z, Li Y, Liu S, Liu F, Li Z. A facile method to prepare high molecular weight bio-renewable poly(γ-butyrolactone) using a strong base/urea binary 23. Diedrich CM, Guler Z, Hympanova L, Vodegel E, Zundel M, Mazza E, et al. synergistic catalytic system. Polym Chem. (2019) 10:1231–7. doi: 10.1039/c8py01812j Evaluation of the short-term host response and biomechanics of an absorbable poly-4-hydroxybutyrate scaffold in a sheep model following vaginal implantation. 3. Yuan S, Sun X, Shen Y, Li Z. Bioabsorbable poly(4-hydroxybutyrate) (P4HB) BJOG. (2022) 129:1039–49. doi: 10.1111/1471-0528.17040 fibrous membranes as a potential dermal substitute. J Mater Chem B. (2021) 9 (38):8074–80. doi: 10.1039/d1tb01271a 24. O’Shaughnessy D, Grande D, El-Neemany D, Sajjan S, Pillalamarri N, Shalom D, et al. Evaluation of the histological and biomechanical properties of poly-4-hydroxybutyrate 4. Hong M, Chen EY. Towards truly sustainable polymers: a metal-free recyclable scaffold for pelvic organ prolapse, compared with polypropylene mesh in a rabbit model. polyester from biorenewable non-strained gamma-butyrolactone. Angew Chem Int Int Urogynecol J. (2021) 33(8):2213–20. doi: 10.1007/s00192-021-04851-6 Ed Engl. (2016) 55(13):4188–93. doi: 10.1002/anie.201601092 25. Rostaminia G. A commentary on “evaluation of the histological and 5. Williams SF, Rizk S, Martin DP. Poly-4-hydroxybutyrate (P4HB): a new biomechanical properties of poly-4-hydroxybutyrate (P4HB) scaffold for pelvic generation of resorbable medical devices for tissue repair and regeneration. Biomed organ prolapse, as compared to polypropylene mesh in a rabbit model”. Int Tech (Berl). (2013) 58(5):439–52. doi: 10.1515/bmt-2013-0009 Urogynecol J. (2021) 33(8):2221. doi: 10.1007/s00192-021-04944-2 6. Martin DP, Badhwar A, Shah DV, Rizk S, Eldridge SN, Gagne DH, et al. 26. Verhorstert KWJ, Guler Z, de Boer L, Riool M, Roovers JWR, Zaat SAJ, et al. The Characterization of poly-4-hydroxybutyrate mesh for hernia repair applications. impact of bacterial contamination on the host response towards fully absorbable poly- J Surg Res. (2013) 184(2):766–73. doi: 10.1016/j.jss.2013.03.044 4-hydroxybutyrate and nonabsorbable polypropylene pelvic floor implants. Mater 7. Williams SF, Martin DP, Moses AC. The history of GalaFLEX P4HB scaffold. Today Bio. (2022) 15:100268. doi: 10.1021/acsami.0c14668 Aesthet Surg J. (2016) 36(suppl 2):S33–42. doi: 10.1093/asj/sjw141 27. Faulkner JD, Bilezikian JA, Beeson ST, Jernigan R, Fox SS, Hope WW. 8. Singhi B, Ford EN, King MW. The effect of wet spinning conditions on the Evaluation of absorbable mesh for prophylactic mesh augmentation in high-risk structure and properties of poly-4-hydroxybutyrate fibers. J Biomed Mater Res Part patients. Surg Technol Int. (2021) 38:213–7. doi: 10.52198/21.STI.38.HR1430 B Appl Biomater. (2021) 109(7):982–9. doi: 10.1002/jbm.b.34763 28. Aldohayan A, Bamehriz F, Khalid Alghamdi G, Ahmed AlJunidel R, AlBalawi 9. Instructions for Use—Phasix Mesh, C. R. Bard, Inc. (Warwick, RI), accessed M, Zakaria Aldhayan A, et al. A novel use of fully absorbable phasix(TM) mesh for electronically 2017. laparoscopic inguinal hernia repair. J Soc Laparoendosc Surg/Soc Laparoendosc Surg. (2020) 24(3):e2020.00041. doi: 10.04293/JSLS.02020.00041 10. Instructions for Use—Phasix ST Mesh, C. R. Bard, Inc. (Warwick, RI), accessed electronically 2017. 29. Panici Tonucci T, Asti E, Sironi A, Ferrari D, Bonavina L. Safety and efficacy of crura augmentation with phasix ST mesh for large hiatal hernia: 3-year single-center 11. van Driel LJ, Miserez M, Aarts F, Tollens T. Observational cohort study on the experience. J Laparoendosc Adv Surg Tech A. (2020) 30(4):369–72. doi: 10.1089/lap. use of a slowly fully resorbable synthetic mesh (phasixTM) in the treatment of complex 2019.0726 abdominal wall pathology with different grades of contamination. Surg Technol Int. 30. Buell J, Flaris A, Raju S, Hauch A, Darden M, Parker G. Long-term outcomes in (2021) 38:186–92. doi: 10.52198/21.sti.38.hr1418 complex abdominal wall reconstruction repaired with absorbable biologic polymer 12. Hope WW, El-Ghazzawy AG, Winterstein BA, Blatnik JA, Davis SS, Greenberg scaffold (poly-4-hydroxybutyrate). Ann Surg. (2021) 1(e032):1–7. doi: 10.1097/as9. JA, et al. A prospective, multicenter trial of a long-term bioabsorbable mesh with sepra 0000000000000032 technology in cohort of challenging laparoscopic ventral or incisional hernia repairs 31. Roth JS, Anthone GJ, Selzer DJ, Poulose BK, Pierce RA, Bittner JG, et al. Long- (ATLAS trial). Ann Med Surg (Lond). (2022) 73:103156. doi: 10.1016/j.amsu.2021. term, prospective, multicenter study of P4HB (phasixTM) mesh for hernia repair in 103156 cohort at risk for complications: 60-months follow-up. J Am Coll Surg. (2022) 13. Adams WP J, Moses AC. Use of poly-4-hydroxybutyrate mesh to optimize soft- 1:894–904. doi: 10.1097/XCS.0000000000000363 tissue support in mastopexy: a single-site study. Plast Reconstr Surg. (2017) 139 32. Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D, et al. PRISMA (1):67–75. doi: 10.1097/PRS.0000000000002922 extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern 14. Wormer BA, Clavin NW, Lefaivre JF, Korn JM, Teng E, Aukskalnis AS, et al. Med. (2018) 169(7): 467–73. doi: 10.7326/M18-0850 Reducing postoperative abdominal bulge following deep inferior epigastric 33. Surgical Site Infection Event Protocol, Centers for Disease Control and perforator flap breast reconstruction with onlay monofilament poly-4- Prevention (CDC). https://wwwcdcgov/nhsn/pdfs/pscmanual/9pscssicurrentpdf hydroxybutyrate biosynthetic mesh. J Reconstr Microsurg. (2017) 33(1):8–18. (Accessed February 15, 2017). 1–31. doi: 10.1055/s-0036-1586495 34. Breuing K, Butler CE, Ferzoco S, Franz M, Hultman CS, Kilbridge JF, et al. 15. Levy AS, Bernstein JL, Xia JJ, Otterburn DM. Poly-4-hydroxybutyric acid mesh Incisional ventral hernias: review of the literature and recommendations regarding compares favorably with acellular dermal matrix in tissue expander-based breast the grading and technique of repair. Surgery. (2010) 148(3):544–58. doi: 10.1016/j. reconstruction. Ann Plast Surg. (2020) 85(S1):S2–7. doi: 10.1097/SAP.0000000 000002339 surg.2010.01.008 16. Adams WP J, Toriumi DM, Van Natta BW. Clinical use of GalaFLEX in facial 35. Kanters AE, Krpata DM, Blatnik JA, Novitsky YM, Rosen MJ. Modified hernia and breast cosmetic plastic surgery. Aesthet Surg J. (2016) 36(Suppl 2):S23–32. doi: 10. grading scale to stratify surgical site occurrence after open ventral hernia repairs. J Am 1093/asj/sjw142 Coll Surg. (2012) 215(6):787–93. doi: 10.1016/j.jamcollsurg.2012.08.012 17. Baxter R. Internal bra: a unifying solution for reconstructive and aesthetic breast 36. Pineda Molina C, Hussey GS, Eriksson J, Shulock MA, Cardenas Bonilla LL, surgery issues. Plast Aesthet Res. (2016) 3:3–7. doi: 10.20517/2347-9264.2015.68 Giglio RM, et al. 4-Hydroxybutyrate promotes endogenous antimicrobial peptide 18. Adams WP J, Baxter R, Glicksman C, Mast BA, Tantillo M, Van Natta BW. The expression in macrophages. Tissue Engr Part A. (2019) 25:693–706. doi: 10.1089/ use of poly-4-hydroxybutyrate (P4HB) scaffold in the ptotic breast: a multicenter ten.tea.2018.0377 clinical study. Aesthet Surg J. (2018) 38(5):502–18. doi: 10.1093/asj/sjy022 37. Pineda Molina C, Giglio R, Gandhi RM, Sicari BM, Londono R, Hussey GS, et al. 19. Calobrace MB, Mays C, Wilson R, Wermeling R. Popcorn capsulorrhaphy in Comparison of the host macrophage response to synthetic and biologic surgical revision aesthetic breast surgery. Aesthet Surg J. (2020) 40(1):63–74. doi: 10.1093/asj/sjy324 meshes used for ventral hernia repair. J Immunol Regen Med. (2019) 3:13–25. doi: 10.1016/j.regen.2018.12.002 20. Mallucci P, Bistoni G. Experience and indications for the use of the P4HB scaffold (galaflex) in aesthetic breast surgery: 100 case experience. Aesthet Surg J. (2022) 42 38. Trapani V, Bagni G, Piccoli M, Roli I, Di Patti F, Arcangeli A. Analysis of (12):1394–405. doi: 10.1093/asj/sjac198 resorbable mesh implants in short-term human muscular fascia cultures: a pilot study. Hernia. (2020) 24(6):1283–91. doi: 10.1007/s10029-020-02271-x 21. Sigalove S, O’Rorke E, Maxwell GP, Gabriel A. Evaluation of the safety of a GalaFLEX-AlloDerm construct in prepectoral breast reconstruction. Plast Reconstr 39. Verhorstert KWJ, Guler Z, de Boer L, Riool M, Roovers JWR, Zaat SAJ. In vitro Surg. (2022) 150:75S–81S. doi: 10.1097/PRS.0000000000009520 bacterial adhesion and biofilm formation on fully absorbable poly-4-hydroxybutyrate Frontiers in Surgery 17 frontiersin.org Deeken et al. 10.3389/fsurg.2023.1157661 and nonabsorbable polypropylene pelvic floor implants. ACS Appl Mater Interfaces. 60. Pakula A, Skinner R. Outcomes of open complex ventral hernia repairs with (2020) 12(48):53646–53. doi: 10.1021/acsami.0c14668 retromuscular placement of poly-4-hydroxybutyrate bioabsorbable mesh. Surg Innov. (2020) 27(1):32–7. doi: 10.1177/1553350619881066 40. Diedrich CM, Roovers JP, Smit TH, Guler Z. Fully absorbable poly-4- hydroxybutyrate implants exhibit more favorable cell-matrix interactions than 61. Rehnke RD, Schusterman MA 2nd, Clarke JM, Price BC, Waheed U, Debski RE, polypropylene. Mater Sci Eng C Mater Biol Appl. (2021) 120:111702. doi: 10.1016/j. et al. Breast reconstruction using a three-dimensional absorbable mesh scaffold and msec.2020.111702 autologous fat grafting: a composite strategy based on tissue-engineering principles. Plast Reconstr Surg. (2020) 146(4):409e–13e. doi: 10.1097/PRS.0000000000007172 41. Mora-Navarro C, Ozpinar EW, Sze D, Martin DP, Freytes DO. Transcriptome- targeted analysis of human peripheral blood-derived macrophages when cultured on 62. Rognoni C, Cuccurullo D, Borsoi L, Bonavina L, Asti E, Crovella F, et al. Clinical biomaterial meshes. Biomed Mater. (2021) 16(2):025006. doi: 10.1088/1748-605X/ outcomes and quality of life associated with the use of a biosynthetic mesh for abdbdb complex ventral hernia repair: analysis of the “Italian hernia club” registry. Sci Rep. (2020) 10(1):10706. doi: 10.1038/s41598-020-67821-w 42. Pineda Molina C, Hussey GS, Liu A, Eriksson J, D’Angelo WA, Badylak SF. Role of 4-hydroxybutyrate in increased resistance to surgical site infections associated with 63. van Rooijen MMJ, Jairam AP, Tollens T, Jorgensen LN, de Vries Reilingh TS, surgical meshes. Biomaterials. (2021) 267:120493. doi: 10.1016/j.biomaterials.2020. Piessen G, et al. Outcomes of a new slowly resorbable biosynthetic mesh 120493 (phasixTM) in potentially contaminated incisional hernias: a prospective, multi- center, single-arm trial. Int J Surg. (2020) 83:31–6. doi: 10.1016/j.ijsu.2020.08.053 43. Deeken CR, Matthews BD. Characterization of the mechanical strength, resorption properties, and histologic characteristics of a fully absorbable material 64. Yu D, Patel AT, Rossi K, Topham NS, Chang EI. Comparison of phasix, (poly-4-hydroxybutyrate-PHASIX mesh) in a porcine model of hernia repair. ISRN polypropylene, and primary closure of the abdominal donor site after bilateral free Surg. (2013) 2013:238067. doi: 10.1155/2013/238067 flap breast reconstruction: long-term evaluation of abdominal hernia and bulge 44. Scott JR, Deeken CR, Martindale RG, Rosen MJ. Evaluation of a fully absorbable formation. Microsurgery. (2020) 40(4):434–9. doi: 10.1002/micr.30541 poly-4-hydroxybutyrate/absorbable barrier composite mesh in a porcine model of 65. Aldohayan A, Alamri H, Aljunidel R, Alotaibi A, Alosaimi M, Alburakan A, ventral hernia repair. Surg Endosc. (2016) 30(9):3691–701. doi: 10.1007/s00464-016- et al. Laparoscopic ventral hernia repair with poly-4-hydroxybutyrate absorbable 5057-9 barrier composite mesh. J Soc Laparoendosc Surg/Soc Laparoendosc Surg. (2021) 25 45. Stoikes NFN, Scott JR, Badhwar A, Deeken CR, Voeller GR. Characterization of (1):1–5. doi: 10.4293/JSLS.2020.00105 host response, resorption, and strength properties, and performance in the presence of 66. Bueno-Lledó J, Ceno M, Pérez-Alonso C, Martinez-Hoed J, Pous-Serrano S. bacteria for fully absorbable biomaterials for soft tissue repair. Hernia. (2017) 21 Abdominal wall reconstruction with biosynthetic absorbable mesh after infected (5):771–82. doi: 10.1007/s10029-017-1638-3 prosthesis explantation: single stage is better than two-stage approach of chronic 46. Miserez M, Jairam AP, Boersema GSA, Bayon Y, Jeekel J, Lange JF. Resorbable mesh infection. Hernia. (2020) 25(4):1005–12. doi: 10.1007/s10029-020-02309-0 synthetic meshes for abdominal wall defects in preclinical setting: a literature review. 67. Bueno-Lledó J, Ceno M, Perez-Alonso C, Martinez-Hoed J, Torregrosa-Gallud J Surg Res. (2019) 237:67–75. doi: 10.1016/j.jss.2018.11.054 A, Pous-Serrano S. Biosynthetic resorbable prosthesis is useful in single-stage 47. Deeken CR, Gagne DH, Badhwar A. Mechanical and histological characteristics management of chronic mesh infection after abdominal wall hernia repair. World of phasixTM ST mesh in a porcine model of hernia repair. J Invest Surg. (2020) 35:1–9. J Surg. (2021) 45(2):443–50. doi: 10.1007/s00268-020-05808-4 doi: 10.1080/08941939.2020.1830318 68. Charleux-Muller D, Hurel R, Fabacher T, Brigand C, Rohr S, Manfredelli S, et al. 48. Pascual G, Rodríguez M, Pérez-Köhler B, Benito-Martínez S, Calvo B, García- Slowly absorbable mesh in contaminated incisional hernia repair: results of a French Moreno F, et al. Long term comparative evaluation of two types of absorbable multicenter study. Hernia. (2021) 25(4):1051–9. doi: 10.1007/s10029-020-02366-5 meshes in partial abdominal wall defects: an experimental study in rabbits. Hernia. 69. Charleux-Muller D, Romain B, Boisson C, Velten M, Brigand C, Lejeune C. (2020) 24(6):1159–73. doi: 10.1007/s10029-020-02201-x Cost-effectiveness analysis of resorbable biosynthetic mesh in contaminated ventral 49. Pascual G, Benito-Martínez S, Rodríguez M, Pérez-Köhler B, García-Moreno F, hernia repair. J Visc Surg. (2021) 159(4):29–295. doi: 10.1016/j.jviscsurg.2021.06.001 Bellón JM. Behaviour at the peritoneal interface of next-generation prosthetic 70. Christopher AN, Morris MP, Patel V, Mellia JA, Fowler C, Messa CA 4th, et al. materials for hernia repair. Surg Endosc. (2022) 36(1):579–90. doi: 10.1007/s00464- An evaluation of clinical and quality of life outcomes after ventral hernia repair with 021-08320-5 poly-4-hydroxybutyrate mesh. Hernia. (2021) 25(3):717–26. doi: 10.1007/s10029-021- 50. Buell JF, Sigmon D, Ducoin C, Shapiro M, Teja N, Wynter E, et al. Initial 02394-9 experience with biologic polymer scaffold (poly-4-hydroxybuturate) in complex 71. Christopher AN, Patel V, Othman S, Jia H, Mellia JA, Broach RB, et al. Onlay abdominal wall reconstruction. Ann Surg. (2017) 266(1):185–8. doi: 10.1097/SLA. poly-4-hydroxybutyrate (P4HB) mesh for complex hernia: early clinical and patient 0000000000001916 reported outcomes. J Surg Res. (2021) 264:199–207. doi: 10.1016/j.jss.2021.02.012 51. Plymale MA, Davenport DL, Dugan A, Zachem A, Roth JS. Ventral hernia repair 72. Christopher AN, Morris MP, Jia H, Broach R, Fischer JP. Resorbable synthetic with poly-4-hydroxybutyrate mesh. Surg Endosc. (2018) 32(4):1689–94. doi: 10.1007/ ventral hernia repair in contaminated fields: outcomes with poly-4-hydroxybutyrate s00464-017-5848-7 mesh. Plast Reconstr Surg. (2021) 148(6):1367–75. doi: 10.1097/PRS.0000000000 52. Roth JS, Anthone GJ, Selzer DJ, Poulose BK, Bittner JG, Hope WW, et al. 008579 Prospective evaluation of poly-4-hydroxybutyrate mesh in CDC class I/high-risk 73. Claessen JJM, Timmer AS, Atema JJ, Boermeester MA. Outcomes of mid-term ventral and incisional hernia repair: 18-month follow-up. Surg Endosc. (2018) 32 and long-term degradable biosynthetic meshes in single-stage open complex (4):1929–36. doi: 10.1007/s00464-017-5886-1 abdominal wall reconstruction. Hernia. (2021) 26:1–11. doi: 10.1007/s10029-021- 53. van Rooijen MMJ, Jairam AP, Tollens T, Jorgensen LN, de Vries Reilingh TS, 02415-7 Piessen G, et al. A post-market, prospective, multi-center, single-arm clinical 74. Lambrecht M, Tollens T. Successful conservative treatment of a poly-4- investigation of phasix mesh for VHWG grade 3 midline incisional hernia hydroxybutyrate mesh infection: a case report. Ann Med Surg (Lond). (2021) repair: a research protocol. BMC Surg. (2018) 18(1):104. doi: 10.1186/s12893- 63:102162. doi: 10.1016/j.amsu.2021.02.008 018-0439-7 75. Levy AS, Bernstein JL, Premaratne ID, Rohde CH, Otterburn DM, Morrison KA, 54. Kniepeiss D, Waha JE, Auer T, Berghold A, Schemmer P. PRevention of et al. Poly-4-hydroxybutyrate (phasixTM) mesh onlay in complex abdominal wall INCisional hernia after liver transplantation (PRINC trial): study protocol for a repair. Surg Endosc. (2021) 35(5):2049–58. doi: 10.1007/s00464-020-07601-9 randomized controlled trial. Trials. (2019) 20(1):371. doi: 10.1186/s13063-019-3477-2 76. Roth JS, Anthone GJ, Selzer DJ, Poulose BK, Pierce RA, Bittner JG, Hope WW, 55. Messa CA, Kozak G, Broach RB, Fischer JP. When the mesh goes away: an et al. Prospective, multicenter study of P4HB (phasix) mesh for hernia repair in cohort analysis of poly-4-hydroxybutyrate mesh for complex hernia repair. Plast Reconstr at risk for complications: 3-year follow-up. Ann Med Surg (Lond). (2020) 61:1–7. Surg Glob Open. (2019) 7(11):e2576. doi: 10.1097/GOX.0000000000002576 doi: 10.1016/j.amsu.2020.12.002 56. Nair NM, Mills DC. Poly-4-hydroxybutyrate (P4HB) scaffold internal support: 77. van Rooijen MMJ, Tollens T, Jorgensen LN, de Vries Reilingh TS, Piessen G, preliminary experience with direct implant opposition during complex breast Kockerling F, et al. Slowly resorbable biosynthetic mesh: 2-year results in revisions. Aesthet Surg J. (2019) 39(11):1203–13. doi: 10.1093/asj/sjy276 VHWG grade 3 hernia repair. Hernia. (2021) 26(1):131–8. doi: 10.1007/s10029- 57. Abdelmoaty WF, Dunst CM, Filicori F, Zihni AM, Davila-Bradley D, Reavis KM, 021-02453-1 et al. Combination of surgical technique and bioresorbable mesh reinforcement of the 78. Vauclair E, Bert M, Facy O, Cheynel N, Rat P, Ortega-Deballon P. What results crural repair leads to low early hernia recurrence rates with laparoscopic can be expected one year after complex incisional hernia repair with biosynthetic paraesophageal hernia repair. J Gastroint Surg. (2020) 24(7):1477–81. doi: 10.1007/ mesh? J Visc Surg. (2021) 158(2):111–7. doi: 10.1016/j.jviscsurg.2020.07.008 s11605-019-04358-y 79. Aiolfi A, Cavalli M, Sozzi A, Lombardo F, Lanzaro A, Panizzo V, et al. Medium- 58. Aiolfi A, Cavalli M, Saino G, Sozzi A, Bonitta G, Micheletto G, et al. term safety and efficacy profile of paraesophageal hernia repair with phasix-ST((R)) Laparoscopic posterior cruroplasty: a patient tailored approach. Hernia. (2022) 26 mesh: a single-institution experience. Hernia. (2022) 26(1):279–86. doi: 10.1007/ (2):619–26. doi: 10.1007/s10029-020-02188-5 s10029-021-02528-z 59. Mellia JA, Othman S, Naga HI, Messa CA 4th, Elfanagely O, Byrnes YM, et al. 80. Konstantinidis H, Charisis C. Surgical treatment of large and complicated hiatal Outcomes of poly-4-hydroxybutyrate mesh in ventral hernia repair: a systematic hernias with the new resorbable mesh with hydrogel barrier (phasix ST): a preliminary review and pooled analysis. Plast Reconstr Surg Glob Open. (2020) 8(12):e3158. study. J Robot Surg. (2022) 17:141–6. doi: 10.1007/s11701-022-01406-9 doi: 10.1097/GOX.0000000000003158 Frontiers in Surgery 18 frontiersin.org Deeken et al. 10.3389/fsurg.2023.1157661 81. Layer T, Benammi S, Dubuisson V, Manfredelli S, Passot G, Charleux-Muller D, 89. Lake SP, Stoikes NFN, Badhwar A, Deeken CR. Contamination of hybrid hernia et al. Incisional hernia repair with a slowly absorbable P4HB mesh: what happens after meshes compared to bioresorbable phasix mesh in a rabbit subcutaneous implant the mesh disappears? A retrospective longitudinal clinical study. Hernia. (2022). inoculation model. Ann Med Surg (Lond). (2019) 46:12–6. doi: 10.1016/j.amsu.2019. (Online only) doi: 10.1007/s10029-022-02616-8 08.004 82. Lima DL, Estrada A, Pereira X, Alcabes A, Sreeramoju P, Malcher F. Versatility 90. Levy AS, Bernstein JL, Premaratne ID, Rohde CH, Otterburn DM, Morrison KA, of poly-4-hydroxybutyrate (phasix) mesh in abdominal wall surgery. Arq et al. Poly-4-hydroxybutyrate (phasix) mesh onlay in complex abdominal wall repair. Gastroenterol. (2022) 59(2):226–30. doi: 10.1590/S0004-2803.202202000-41 Surg Endosc. (2020) 35(5):2049–58. doi: 10.1007/s00464-020-07601-9 83. Othman S, Christopher A, Patel V, Jia H, Mellia JA, Kovach SJ, et al. Comparative 91. Kokotovic D, Bisgaard T, Helgstrand F. Long-term recurrence and complications effectiveness analysis of resorbable synthetic onlay and biologic intraperitoneal mesh for associated with elective incisional hernia repair. JAMA. (2016) 316(15):1575–82. abdominal wall reconstruction: a 2-year match-paired analysis. Plast Reconstr Surg. doi: 10.1001/jama.2016.15217 (2022) 149(5):1204–13. doi: 10.1097/PRS.0000000000009021 92. Carbonell AM, Criss CN, Cobb WS, Novitsky YW, Rosen MJ. Outcomes of 84. Schecter SC, Imhoff L, Lasker MV, Hornbeck S, Flores HC. Single-stage synthetic mesh in contaminated ventral hernia repairs. J Am Coll Surg. (2013) 217 abdominal wall reconstruction in contaminated and dirty wounds is safe: a single (6):991–8. doi: 10.1016/j.jamcollsurg.2013.07.382 center experience. Surg Endosc. (2022) 36(8):5766–71. doi: 10.1007/s00464-022- 09058-4 93. Warren J, Desai SS, Boswell ND, Hancock BH, Abbad H, Ewing JA, et al. Safety and efficacy of synthetic mesh for ventral hernia repair in a contaminated field. J Am 85. Talwar AA, Perry NJ, McAuliffe PB, Desai AA, Thrippleton S, Broach RB, et al. Coll Surg. (2020) 230(4):405–13. doi: 10.1016/j.jamcollsurg.2019.12.008 Shifting the goalpost in ventral hernia care: 5-year outcomes after ventral hernia repair with poly-4-hydroxybutyrate mesh. Hernia. (2022) 26:1635–43. doi: 10.1007/s10029- 94. Burger JW, Luijendijk RW, Hop WC, Halm JA, Verdaasdonk EG, Jeekel J. Long- 022-02674-y term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernia. Ann Surg. (2004) 240(4):578–83. doi: 10.1097/01.sla.0000141193. 86. Berrevoet F. The transition from experimental data to clinical practice using 08524.e7 P4HB mesh in ventral hernia repair. J Invest Surg. (2020) 35:1–2. doi: 10.1080/ 08941939.2020.1849467 95. Rosen MJ, Bauer JJ, Harmaty M, Carbonell AM, Cobb WS, Matthews BD, et al. 87. Haddock NT, Suszynski TM, Teotia SS. Discussion: breast reconstruction using a Multicenter, prospective, longitudinal study of the recurrence, surgical site infection, three-dimensional absorbable mesh scaffold and autologous fat grafting: a composite and quality of life after contaminated ventral hernia repair using biosynthetic strategy based on tissue-engineering principles. Plast Reconstr Surg. (2020) 146 absorbable mesh: the COBRA study. Ann Surg. (2017) 265:205–11. doi: 10.1097/ (4):414e–5e. doi: 10.1097/PRS.0000000000007175 SLA.0000000000001601 88. Morales-Conde S, Berrevoet F, Jorgensen LN, Marchi D, Ortega-Deballon P, 96. Itani KM, Rosen M, Vargo D, Awad SS, Denoto G 3rd, Butler CE, et al. Windsor A. Establishing peer consensus about the use of long-term biosynthetic Prospective study of single-stage repair of contaminated hernias using a biologic absorbable mesh for hernia (grades 2–3) as the standard of care. World J Surg. porcine tissue matrix: the RICH study. Surgery. (2012) 152(3):498–505. doi: 10. (2022) 46:2996–3004. doi: 10.1007/s00268-022-06743-2 1016/j.surg.2012.04.008 Frontiers in Surgery 19 frontiersin.org