Technical Note All-Arthroscopic Nanofractured Autologous Matrix- Induced Chondrogenesis (A-NAMIC) Technique for the Treatment of Focal Chondral Lesions of the Knee Juan Manuel Peñalver, M.B., Jordi Villalba, Ph.D., Christian P. Yela-Verdú, M.B, Joel Sánchez, M.B., and Mariano Balaguer-Castro, Ph.D. Abstract: Nanofractured autologous matrix-induced chondrogenesis (NAMICÓ) is a 1-step technique that combines nanofracture needling to induce bone marrow stimulation (BMS) and the use of cell-free collagen matrix to optimize cartilage regeneration. In this Technical Note, we describe a modification of the NAMIC procedure using mosaicplasty trephines to prepare the lesion surface and to shape collagen implants in an all-arthroscopic approach (A-NAMIC). This technique is indicated for the treatment of International Cartilage Repair Society grade III to IV knee chondral lesions of 4 cm2. After damaged cartilage is debrided, trephines are used to create a flat, circular lesion surfaces. Subsequently, BMS is performed with nanofracture, eliciting reproducible and stop-controlled subchondral bone perforations of 9-mm depth and 1-mm width. The collagen membrane is then cut to size with the trephine, placed over the prepared defect, and secured with fibrin glue, preventing loss of regenerating cells and growth factors to the joint space. Using trephines allows the rapid and precise creation of smooth defect surfaces with known dimensions, ensuring optimal lesion coverage. Additionally, nanofracture reduces trabecular compaction and allows for a deeper access to subchondral bone in com- parison with conventional microfracture, improving lesion filling and production of cartilage with higher hyaline content. A rticular cartilage defects remain challenging clin- ical treatment problems for orthopaedic surgeons and, if left untreated, can progress to degenerative technique, first described by Steadman et al.4 Microfracture introduces perforations in the exposed subchondral bone, inducing bleeding and recruitment of osteoarthritis, knee pain, and ultimately loss of func- pluripotential stem cells to the joint surface that will tion.1 The limited self-healing ability of articular carti- differentiate into cartilage-producing chondrocytes.5 lage is due to its avascular nature and slow extracellular However, these procedures typically lack medium- to matrix turnover, along with the limited capacity of long-term durability, particularly in cases of larger lesions, resident chondrocytes to migrate to damaged areas.2 because of progressive ossification and limited biome- Cartilage repair techniques based on bone marrow chanical properties of the regenerated tissue.6 mesenchymal stem cells (MSCs) have been widely used An evolution of this method is autologous matrix- since first introduced in the 1950s.3 The most frequently induced chondrogenesis (AMIC),7,8 which combines used method for using stem cells is the microfracture microfracture with the application of a collagen matrix membrane over the treated defect to serve as a scaffold for stem cells, allowing effective reconstruction of larger From the Knee Unit, Department of Orthopedic Surgery and Traumatology, defects. The AMIC procedure can be performed with either Parc Taulí University Hospital Institut d’Investigació i Innovació Parc Taulí an open approach7 or as an all-arthroscopic surgery.8 In CSPT, Autonomous University of Barcelona, Sabadell, Spain. the latter, the authors also introduced the use of mosaic- The authors report that they have no conflicts of interest in the authorship plasty trephines to prepare the lesion surface and cut the and publication of this article. Full ICMJE author disclosure forms are available for this article online, as supplementary material. matrix implant to size. Midterm studies on microfracturing Received November 18, 2019; accepted February 4, 2020. and the AMIC have shown encouraging results.9 Address correspondence to Dr. J.M. Peñalver, Plaça del Progrés, 24, 08224, Recently, Benthien et al.10 introduced a further Terrassa, Barcelona, Spain. E-mail: juanmapenalver@gmail.com development with the nanofractured autologous Ó 2020 by the Arthroscopy Association of North America. Published by matrix-induced chondrogenesis (NAMICÓ) technique, Elsevier. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). in which a new subchondral needling procedure 2212-6287/191409 (NanofractureÒ, Arthrosurface, Franklin, MA) is used https://doi.org/10.1016/j.eats.2020.02.007 instead of microfracture. Nanofracture creates smaller Arthroscopy Techniques, Vol 9, No 6 (June), 2020: pp e755-e759 e755 e756 J. M. PEÑALVER ET AL. and deeper cell channels and in a more reproducible determined, previous publications point to a decrease in way than a standard microfracture, therefore increasing bone marrow MSC cell number and regenerative bone marrow access and achieving improved cartilage- capacity in older patients.5 Accordingly, the clinical resurfacing properties.2 In this Technical Note, we success rate of bone marrow stimulationebased treat- provide a detailed description of a trephine-assisted ments has been most consistent in patients 40 years.5 all-arthroscopic NAMIC (A-NAMIC) technique for the Magnetic resonance imaging (MRI) T2 mapping and treatment of International Cartilage Repair Society standard radiographic evaluation including standing (ICRS) Grade III/IV focal chondral lesions of the knee. anteroposterior and lateral radiographs are recom- mended. A Rosenberg view should also be performed to Technique assess the main weightbearing area, and in case of Indications for trephine-assisted A-NAMIC are clinical hints for leg axis deviation, an orthodiagram symptomatic full-thickness ICRS grade III or IV focal could be helpful. chondral defects without extensive subchondral bony Surgery on the knee is performed under general deficiency, and a lesion size of 4 cm2 and 5-mm anesthesia with the patient positioned supine on a depth,5 lying in regions of the joint allowing direct standard operation table. A pneumatic tourniquet is access to mosaicplasty trephines (coring reamer). Con- placed at the root of the thigh, and a padded lateral traindications include partial-thickness defects, kissing support is used to allow the application of a valgus force lesions, and widespread articular and joint degenera- to open the medial joint. Standard anterolateral and tion. Although the age limit for A-NAMIC is not yet anteromedial portals are used as viewing and working Fig 1. All-arthroscopic nanofractured autologous matrix-induced chondrogenesis (A-NAMIC) treatment of focal chondral le- sions of the knee. Surgery was performed in the left knee joint with the patient positioned supine and using anterolateral and anteromedial portals as visualization and working portals, respectively. (A) Localization of a grade III full-thickness knee chondral lesion (black arrow). (B) Removal of damaged cartilage (black arrow) and sclerotic bone with an open curette. (C) Image showing the spiral configuration of the 9-mm-depth and 1-mm-diameter nanofracture-performed channels (black arrow). The white arrow indicates the well-defined healthy cartilage margins after debridement of damaged cartilage. (D) Implantation of the 3D I/III collagen membrane with 8- and 10-mm-diameter mosaicplasty trephines (black arrow). (E) Final examination to ensure that the lesion is fully covered by the membrane. Black arrows indicate the 2 implants in their final position. (F) Fibrin sealing. The black arrow indicates the final appearance of the lesion after application of the fibrin glue. MC, medial condyle. A-NAMIC FOR FOCAL CHONDRAL LESIONS OF THE KNEE e757 Table 1. Step-by-Step Summary of A-NAMIC Technique Step Description Observations 1 Position patient supine on a standard operation Use a padded lateral support to apply valgus force. table. 2 Place the pneumatic tourniquet at the roof of the thigh. 3 Establish anterolateral and anteromedial portals as The working portal is positioned depending on the viewing and working portals, respectively. location of the articular cartilage defect to provide optimal, direct access to the cartilage lesion. 4 Evaluate the extent of the cartilage lesion as well as meniscal and cruciate ligament defects. 5 Debride damaged cartilage and remove sclerotic Use sharp curette and a shaver. bone plate. 6 Give a circular shape to the defect surface. Use a trephine of adequate diameter. Create well- defined, healthy vertical edges surrounding the defect. 7 Perform nanofracture. Place the 1-mm Nitinol needle into the lumen of a 15 -angled, cannulated pick. Perform multiple taps with a mallet. Follow spiral pattern to cover the whole lesion area. 8 Repeat the process at 2- to 3-mm intervals. Allow adequate bone bridges between each channel to protect the mechanical stability of subchondral bone. 9 Wash the joint to remove any cartilage debris and loose bony particles. 10 Turn the irrigation pump off and dry the joint. Use a small gauze pad. 11 Rehydrate the type I/III collagen and elastine Use a 10-mm mosaicplasty trephine (coring membrane with physiological saline and cut to reamer) to cut the membrane. size. 12 Place the circular implant in the trephine and slide The membrane has a 2-sided appearance; the down the trephine pusher to the lesion surface. smooth side faces the joint, and the fibrous, rough side faces the cartilage defect. 13 Press the membrane into the defect. The membrane implant must be slightly undersized on the surface of the cartilage defect to retain the membrane in place. 14 For larger defects (>10 mm), repeat the operation The implants can be repositioned with the help of until the cartilage lesion is fully covered. an arthroscopic probe. 15 Seal the lesion with fibrin glue. Use a 19-gauge needle to apply the glue. 16 Perform 10 knee movements to check that the Perform flexion and extension. membrane remains in place. portals, respectively, with the latter being positioned defect surfaces >10 mm, additional reconstruction depending on the location of the articular cartilage areas are prepared using appropriate trephines, trying defect to provide optimal access to the cartilage lesion. to prevent the unnecessary debridement of surround- A thorough examination of the knee joint is then per- ing healthy cartilage. formed to evaluate the extent of the cartilage lesion as Once the defect preparation is completed, nano- well as meniscal and cruciate ligament defects (Fig 1A). fracture is performed by placing the 1-mm needle After assessment of the associated defects, all the (PleuriStik Guide Wire; Arthrosurface) into the lumen damaged cartilage is debrided down to the subchondral of a 15 -angled, cannulated pick (Arthrosurface), and bone plate with an open curette and a shaver, creating a the distal tip of the pick is then placed onto the target contained lesion with well-defined healthy vertical site. With a mallet, multiple taps are made on the edges surrounding the defect (Fig 1B). At this point, the proximal head of the needle, driving the tip into the chondral defect is addressed as described by Piontek subchondral bone and obtaining standardized and stop- et al.8 Accordingly, the lesion is sized with a 5-mm controlled 9-mm-depth and 1-mm-diameter channels. probe or a mosaicplasty trephine of the appropriate The needle is then removed with the thumb tab diameter (6-, 8-, or 10-mm-diameter mosaicplasty accessory (Arthrosurface), and the process is repeated trephine; Arthrex, Naples, FL). The diameter-selected at 2- to 3-mm intervals, allowing adequate bone bridges trephine is then used to create a flat, circularly shaped between each channel to protect the mechanical sta- defect surface with known dimensions that will ulti- bility of the subchondral bone. Subchondral needling is mately accommodate the membrane implant. For started from the periphery of the lesion and then e758 J. M. PEÑALVER ET AL. Table 2. Risks and Limitations ICRS Grade III focal chondral lesion of the knee is Risks shown in the Video and summarized in Table 1. - Membrane mispositioning Weightbearing is restricted for 6 weeks after surgery, - Implant instability due to implant oversizing since this may lead to displacement of the collagen - Uncovered lesion areas due to implant undersizing - Longer ischemic times compared with the open surgery procedure membrane and poorer tissue integration, and moving Limitations around with crutches is encouraged. Continuous pas- - Direct access to lesion required; adapt working portal position sive movement (CPM) is recommended daily to pre- - Difficult access to lesion in some knee areas (posterior condyle or vent joint stiffness and improve early motion, starting patella lesions) 48 h after surgery, with initial settings ranging from - Highly demanding arthroscopic technique - Osteochondral lesions >3 mm in depth require subchondral bone 0 to 40 . The range of motion (ROM) is then daily reconstruction with autograft increased as tolerated until 90 of flexion is restored. - Need for specific instruments for precise shaping and sizing Partial weightbearing is initiated at 7 weeks. High- - Direct membrane implantation without previous trial impact sports are not recommended, but light sporting activities (swimming, cycling) are allowed. Isotonic and continued toward the center of the lesion following a isometric exercises to potentiate quadriceps and ham- systematic, spiral pattern (Fig 1C). strings strength are also recommended. High-impact After perforation of the subchondral bone, the joint is sports are allowed at 12 months. washed to remove any cartilage debris and loose bony particles. The irrigation pump is turned off, and the Discussion joint is dried with the help of a small gauze pad. The Therapies based on AMIC combine BMS with lesion prepared cartilage defect is then covered with a biode- coverage by a commercially available collagen I/III gradable, cell-free, type I/III collagen and elastine matrix.7 These techniques have been proven to membrane of porcine origin (Cartimaix; Matricel, improve treatment success.9 Microfracture is the most Herzogenrath, Germany) to keep released bone widespread technique to induce MSC recruitment to marrow cells within the defect area. For this purpose, the joint surface. However, microfracturing is not a the collagen membrane is removed from the sterile reproducible procedure, making it difficult to compare packaging, rehydrated with physiological saline, and outcomes of different studies and establish optimal cut to size with the same mosaicplasty trephine used to treatment strategies. Accordingly, there is great vari- shape the defect surface. The membrane has a 2-sided ability in the depth and diameter of the microfracture appearance: the smooth side (which is marked with a perforations depending on factors such as the shape and sterile pen to facilitate side identification within the size of the awl tip or the force exerted upon it by the joint) faces the joint, whereas the fibrous, rough side surgeon. This is specially relevant considering that faces the cartilage defect. The circular implant is posi- shallow subchondral bone penetration could result in tioned in the trephine with the porous layer facing the suboptimal bone marrow stimulation,2 and excessive lesion, and the trephine pusher is slid down to the hole diameter11 could produce trabecular fragmenta- lesion surface (Fig 1D). The membrane is pressed into tion and intrachannel bone compaction. In this sense, the defect. If the diameter of the cartilage defect does compared with cone-shaped 1.5- to 2-mm-wide and 2- not exceed 10 mm, only 1 patch is used. For larger to 4-mm-depth perforations observed in conventional defects, the operation is repeated with subsequent microfracture, nanofracture showed better bone trephine-sized membrane patches until the whole marrow access with standardized stop-controlled cartilage lesion is fully covered. It is important that the 1-mm-wide channels extending 9 mm into the sub- edges of the lesion are vertical and that the membrane chondral bone.5 This defined length limit is set by the implant is slightly undersized in the surface of the Nitinol needle, as cadaver studies showed that longer cartilage defect, as this will retain the membrane in needles would have a higher risk of wire fracture place. The implants can be repositioned with the help of without necessarily resulting in a better outcome. After an arthroscopic probe to ensure they fit the defect nanofracture, deeper channels improved defect filling, without overlapping onto the surrounding healthy with more hyaline cartilage containing a greater cartilage (Fig 1E). Finally, the lesion is sealed by amount of type II collagen and less type I collagen applying a fibrin glue (Tissel 4 ml; Baxter, Deerfield, IL) compared with shallow marrow access. In an ovine to all membrane-covered areas via a 19-gauge needle model, Zedde et al.12 showed that nanofracture resulted (Fig 1F). The glue is left to set for 5 min. Once the in better restoration of the normal subchondral bone membrane is fixed, 10 knee movements (consisting of architecture at 6 months compared with microfracture. flexion and extension) are performed to check that the Autologous chondrocyte implantation (ACI) and membrane remains in place. matrix-induced autologous chondrocyte implantation All-arthroscopic nanofractured autologous matrix- (MACI) are multistage, complex (timely and costly) induced chondrogenesis (A-NAMIC) treatment of an procedures that consist of chondrocyte harvesting from A-NAMIC FOR FOCAL CHONDRAL LESIONS OF THE KNEE e759 a low-weightbearing region of the joint, its expansion References in vitro, and its reimplantation into the debrided carti- 1. 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Microfracture: released MSCs is stabilized by a mixed collagen type I Surgical technique and rehabilitation to treat chondral and type III matrix, helping to promote early mechan- defects. Clin Orthop Relat Res 2001;391:S362-S369. ical stability and cartilage regeneration. In addition, the 5. Benthien JP, Behrens P. Reviewing subchondral cartilage use of fibrin glue to prevent collagen membrane relo- surgery: Considerations for standardised and outcome cation can provide a supplementary advantage over predictable cartilage remodelling: A technical note. Int sutures, as fibrin glue acts as an additional scaffold for Orthop 2013;37:2139-2145. chondrocytes.7 6. Gobbi A, Karnatzikos G, Kumar A. Long-term results after Finally, the use of mosaicplasty trephines provides a microfracture treatment for full-thickness knee chondral lesions in athletes. Knee Surg Sports Traumatol Arthrosc rapid and precise method to create smooth defect sur- 2014;22:1986-1996. faces with known dimensions. This results in optimal 7. Benthien JP, Behrens P. The treatment of chondral and lesion coverage with the matrix implant, because the osteochondral defects of the knee with autologous defect area has been reshaped with the same mosaic- matrix-induced chondrogenesis (AMIC): Method plasty trephine that is used to cut the collagen matrix. description and recent developments. Knee Surg Sports The purpose of this Technical Note is to provide a step- Traumatol Arthrosc 2011;19:1316-1319. by-step description of the trephine-assisted A-NAMIC 8. Piontek T, Ciemniewska-Gorzela K, Szulc A, Naczk J, surgical procedure for the treatment of knee cartilage Słomczykowski M. All-arthroscopic AMIC procedure for defects. This technique represents a step forward in the repair of cartilage defects of the knee. Knee Surg Sports treatment of ICRS grade III/IV focal chondral lesions of Traumatol Arthrosc 2012;20:922-925. the knee with direct access. The main advantages of this 9. Steinwachs MR, Gille J, Volz M, et al. Systematic review and meta-analysis of the clinical evidence on the use of technique are its reproducibility and cost-efficiency and autologous matrix-induced chondrogenesis in the knee. that it can be performed all-arthroscopically in a single- Cartilage 2019:194760351987084. step procedure. Patients have a higher clinical success 10. Benthien JP, Behrens P. Nanofractured autologous matrix and a much shorter rehabilitation time compared with induced chondrogenesis (NAMICÓ)dFurther develop- the traditional AMIC,10 which may be related to a higher ment of collagen membrane aided chondrogenesis com- rate of defect filling and hyaline properties of the re- bined with subchondral needling: A technical note. Knee generated cartilage. This is especially relevant in lesions 2015;22:411-415. >2 cm2. The main inconveniences are that nano- 11. Eldracher M, Orth P, Cucchiarini M, Pape D, Madry H. fracturing needles sometimes tend to bend and may not Small subchondral drill holes improve marrow stimula- be applied at the correct angle. In addition, the location of tion of articular cartilage defects. Am J Sports Med 2014;42: the chondral lesion could be a limiting factor, considering 2741-2750. 12. Zedde P, Cudoni S, Giachetti G, et al. Subchondral bone that direct access is needed to place the membrane over remodeling: Comparing nanofracture with microfracture. the defect with the trephines. A summary of the key risks An ovine in vivo study. Joints 2016;4:87-93. and limitations of this technique is shown in Table 2. 13. Makris EA, Gomoll AH, Malizos KN, Hu JC, Finally, it would be advisable to perform prospective Athanasiou KA. Repair and tissue engineering tech- long-term randomized trials that compare NAMIC with niques for articular cartilage. Nat Rev Rheumatol 2015;11: other cartilage repair techniques. 21-34.