EDITORIAL published: 31 March 2022 doi: 10.3389/fbioe.2022.891459 Editorial: Emerging Therapeutic Approaches for Repair and Regeneration of Injuries in the Peripheral Nervous System Antonio Salgado 1, Xavier Navarro 2 and Srinivas Madduri 3,4* 1 School of Medicine, University of Minho, Braga, Portugal, 2Department of Cell Biology, Universitat Autònoma de Barcelona, Barcelona, Spain, 3Department of Biomedical Engineering, University of Basel, Basel, Switzerland, 4Department of Surgery, University of Geneva, Geneva, Switzerland Keywords: nerve injury, cell therapy, nerve bioengineering, neurotrophic factors, nerve guidance graft, nano materials, growth factors delivery Editorial on the Research Topic Bio-Systems Engineering for Regulating Nerve Regeneration The research topic entitled “Bio-systems engineering for regulation of nerve regeneration” is focused on new and emerging approaches for promoting nerve regeneration. Acute and chronic nerve injuries often result in the loss of sensory, motor and autonomic functions with variable pathological changes arising from traumatic or non-traumatic forms of injuries. Despite the severe consequences of such injuries for the patients, existing treatment options, i.e., surgical repair, often using autologous nerve grafting, and pharmacological compounds, such as corticosteroids, non-steroidal anti-inflammatory and analgesic drugs, Edited and reviewed by: are all associated with important drawbacks and are far from being optimal solutions. Ranieri Cancedda, Consequently, the quality of patient’s life is poor and the resulting socioeconomic impact is Independent researcher, Genova, Italy huge. Thus, there is a great need for further research to advance with new and innovative *Correspondence: treatment strategies for improving functional recovery and patient wellbeing and to minimize Srinivas Madduri the socioeconomic burden. srinivas.madduri@usb.ch So far, research over the past 100 years has achieved remarkable achievements in the field of nerve regeneration, resulting in the advancement of micro-surgical nerve management, nerve cellular and Specialty section: This article was submitted to molecular biology, nerve guidance scaffolds, cell therapy and nerve tissue engineering. Nevertheless, Tissue Engineering and Regenerative the existing knowledge and translational modalities still remain inadequate for clinical applications. Medicine, Within this context, the collected research articles in this issue represent the work of 62 different a section of the journal authors in the form of three review articles and six original research reports, presenting new and Frontiers in Bioengineering and emerging strategies involving interdisciplinary efforts ranging from cell and molecular biology, Biotechnology engineered nano-micromaterials, bio-active delivery, cell and gene therapy, tissue engineered grafts, Received: 07 March 2022 and complex nerve conduit scaffolds. Taken together, the collected research reports strengthen Accepted: 14 March 2022 existing knowledge in the field and provide further insights to move forward. Published: 31 March 2022 Immediately after traumatic nerve injury, Wallerian degeneration (WD) begins and Schwann Citation: cells play a key role in the subsequent cellular and molecular changes paving the way for axonal Salgado A, Navarro X and Madduri S regrowth. However, there are no reported models for investigating the potential therapeutic (2022) Editorial: Emerging Therapeutic interventions for regulating WD. Elsayed et al., report the establishment and characterization of Approaches for Repair and Regeneration of Injuries in the an in vitro WD model, which would enable further research for basic as well as translational Peripheral Nervous System. applications. Furthermore, their data revealed the beneficial effects of the adipose stem cells as Front. Bioeng. Biotechnol. 10:891459. evidenced by the upregulation of neurotrophic factors (NTFs) and CJUN, which are closely doi: 10.3389/fbioe.2022.891459 associated with the axonal growth program. Frontiers in Bioengineering and Biotechnology | www.frontiersin.org 1 March 2022 | Volume 10 | Article 891459 Salgado et al. Editorial: Peripheral Nerve Regeneration In continuation with WD, topographical guidance in the form permanent loss of motor function. Among all the neurotrophic of physical, biological and electrical signals guide the axonal factors, glial cell line-derived neurotrophic factor (GDNF) is the growth and elongation towards the target organ. To address most potent for the survival and growth of motor axons. In these requirements, Yu et al., Castano et al., and Ferrari et al. another review by Egger et al., recent advances in the field of report on the beneficial effects of micro/nano-patterned GDNF gene therapy are presented, as well as future research functional surfaces and nerve cuff electrodes, respectively. directions emphasizing the importance of the spatio-temporal Micropatterned poly (D,L-lactide-co-caprolactone) films aspects of the therapeutic intervention, such as the location, functionalized with KHI peptide and nerve growth factor timing, dose and duration of GDNF. promoted axo-glial growth and in vivo nerve conduction to a The extracellular matrix composition of nerve tissue is significant level. Furthermore, PLA nanofiber with a 950 nm complex in nature and architecture. Biomaterials and bio- range size and SDF-1/CXCL 12 functionalities demonstrated based research approaches are promising for recapitulating the the potential to overcome the inhibitory substrates and key features and for instructing the sequence of cellular and enhance the growth and migration of olfactory ensheathing molecular events of the axonal regeneration and nerve tissue cells. Interestingly, conductive polymer printed regenerative formation. However, the detailed mechanisms underlying the nerve cuff electrodes optimized with cost-effective fabrication interface regulation between engineered biomaterials and nerve technology resulted in enhanced motor axonal regeneration and tissue components are largely unclear. In a detailed review article, function in rats after 3 months. In brief, materials engineered with Powel et al. present such mechanisms with further information micro/nano patterns and bio-chemical physical functions hold on the cell controllable micro-environment resulting from great promise for further developments aiming for the effective engineered bio-active biomaterials. regulation of axonal elongation over long-gap (i.e., 30–60 mm) In summary, we consider that all the articles included in the nerve injuries and for neuroprostheses. current issue provide new and interesting data and important In their work, Panzer et al. describe the fabrication of bands of insights for further research in the field, particularly regarding the Büngner in the form of tissue engineered micro-tissue. For this, interdisciplinary aspects of nerve repair and regeneration hydrogel-based micro-columns with an inner diameter of 300 μm approaches. The guest editors of this research topic thank all and an outer diameter of 700 μm were used for inducing the Schwan authors once again for their valuable contributions and hope that cells into dense and aligned cellular structures resembling bands of the readers in the field will be inspired by these significant Bünger. Such a promising tissue-engineered approach will enable research findings and expert opinions. future developments towards off-the-shelf production of the aligned micro-tissue. Indeed, one of the major barriers for the production of off-the-shelf bio-based products is existing culture conditions, such AUTHOR CONTRIBUTIONS as xenogeneic serum supplementation. As a potential solution to this problem, Guiotto et al. report on the use of human platelet lysate for SM wrote the editorial and all the authors contributed to reading the culture of adipose stem cell and further proved the synergistic and corrections. SM conceived the idea and gathered all co- function of platelet lysate in combination with extracellular matrix editors within the Editorial. components for nerve tissue engineering applications. These results Conflict of Interest: The authors declare that the research was conducted in the open up a viable and new option for the personalization of cell-based absence of any commercial or financial relationships that could be construed as a therapeutic product development. potential conflict of interest. Growth factors are widely accepted for their key role in regulating tissue growth and development. However, the Publisher’s Note: All claims expressed in this article are solely those of the authors current lack of appropriate delivery scaffolds and strategies has and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in limited their therapeutic potential. In their review, Salvin et al. this article, or claim that may be made by its manufacturer, is not guaranteed or present the therapeutic potential of insulin-like growth factor-1, endorsed by the publisher. known for its trophic and protective effects on neuronal and non- neuronal glial cells. In addition, the review offers important Copyright © 2022 Salgado, Navarro and Madduri. This is an open-access article insights on the most promising delivery routes and dosage distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the forms for supporting nerve regeneration. Spinal root (ventral original author(s) and the copyright owner(s) are credited and that the original root) avulsion is critical and represents the most serious proximal publication in this journal is cited, in accordance with accepted academic practice. nerve injury, given the fact that the distance between the lesion No use, distribution or reproduction is permitted which does not comply with and target innervation site is too long and often results in a these terms. Frontiers in Bioengineering and Biotechnology | www.frontiersin.org 2 March 2022 | Volume 10 | Article 891459