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Barriers to Epineural Scarring: Role in Treatment of Traumatic Nerve Injury and Chronic Compressive Neuropathy

2018; Elsevier BV; Volume: 43; Issue: 4 Linguagem: Inglês

10.1016/j.jhsa.2018.01.013

1531-6564

Christopher J. Dy, Benjamin Aunins, David M. Brogan,

Wound Healing and Treatments

The physiological limitations of neural regeneration make peripheral nerve surgery challenging to both the surgeon and the patient. Presence of nerve gaps and local wound factors may all influence outcome, suggesting that barriers to reduce perineural scarring, minimize fibrosis, and avoid ischemia would be beneficial. To examine the evidence supporting their use, we reviewed the autologous and commercially-available options for barriers against scarring around a nerve. Numerous clinical case series demonstrated the effectiveness and safety of local/rotational flaps and autologous vein wrapping when used in the presence of recurrent compressive neuropathy. Translational research in animal models supports the biocompatibility of commercially available nerve wraps following nerve repair. To date, there are no reports of clinical use of commercially available nerve wraps in acute nerve repair, but a growing number of case series demonstrate their effectiveness and safety in chronic compressive neuropathy. Limited clinical evidence exists to support the efficacy of vein or flap coverage in acute nerve repairs. The physiological limitations of neural regeneration make peripheral nerve surgery challenging to both the surgeon and the patient. Presence of nerve gaps and local wound factors may all influence outcome, suggesting that barriers to reduce perineural scarring, minimize fibrosis, and avoid ischemia would be beneficial. To examine the evidence supporting their use, we reviewed the autologous and commercially-available options for barriers against scarring around a nerve. Numerous clinical case series demonstrated the effectiveness and safety of local/rotational flaps and autologous vein wrapping when used in the presence of recurrent compressive neuropathy. Translational research in animal models supports the biocompatibility of commercially available nerve wraps following nerve repair. To date, there are no reports of clinical use of commercially available nerve wraps in acute nerve repair, but a growing number of case series demonstrate their effectiveness and safety in chronic compressive neuropathy. Limited clinical evidence exists to support the efficacy of vein or flap coverage in acute nerve repairs. When performing nerve repair, a favorable soft tissue envelope would intuitively seem to minimize the chances of ischemia and scar formation that can impede neural regeneration. In the case of revision surgery for chronic compressive neuropathy, surgery in an already scarred tissue bed can create additional adhesions that lead to eventual symptom recurrence and traction-related pain. Ideally, a barrier could be used to promote nerve gliding and reduce scarring around the nerve, without proliferation of extraneural fibrosis and scarring. Scientists and surgeons have provided innovative solutions, ranging from synthetic and xenograft materials to autologous vein wrapping and pedicled/free tissue coverage. There is no clear guidance on which barriers provide the best results in either the acute or the chronic situation or the indications for their use.CME Information and DisclosuresThe Journal of Hand Surgery will contain at least 2 clinically relevant articles selected by the editor to be offered for CME in each issue. For CME credit, the participant must read the articles in print or online and correctly answer all related questions through an online examination. The questions on the test are designed to make the reader think and will occasionally require the reader to go back and scrutinize the article for details.The JHS CME Activity fee of $15.00 includes the exam questions/answers only and does not include access to the JHS articles referenced.Statement of Need: This CME activity was developed by the JHS editors as a convenient education tool to help increase or affirm reader's knowledge. The overall goal of the activity is for participants to evaluate the appropriateness of clinical data and apply it to their practice and the provision of patient care.Accreditation: The ASSH is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.AMA PRA Credit Designation: The American Society for Surgery of the Hand designates this Journal-Based CME activity for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.ASSH Disclaimer: The material presented in this CME activity is made available by the ASSH for educational purposes only. This material is not intended to represent the only methods or the best procedures appropriate for the medical situation(s) discussed, but rather it is intended to present an approach, view, statement, or opinion of the authors that may be helpful, or of interest, to other practitioners. Examinees agree to participate in this medical education activity, sponsored by the ASSH, with full knowledge and awareness that they waive any claim they may have against the ASSH for reliance on any information presented. The approval of the US Food and Drug Administration is required for procedures and drugs that are considered experimental. Instrumentation systems discussed or reviewed during this educational activity may not yet have received FDA approval.Provider Information can be found at https://www.assh.org/About-ASSH/Contact-Us.Technical Requirements for the Online Examination can be found at https://www.jhandsurg.org/cme/home.Privacy Policy can be found at http://www.assh.org/About-ASSH/Policies/ASSH-Policies.ASSH Disclosure Policy: As a provider accredited by the ACCME, the ASSH must ensure balance, independence, objectivity, and scientific rigor in all its activities.Disclosures for this ArticleEditorsDavid Netscher, MD, has no relevant conflicts of interest to disclose.AuthorsAll authors of this journal-based CME activity have no relevant conflicts of interest to disclose. In the printed or PDF version of this article, author affiliations can be found at the bottom of the first page.PlannersDavid Netscher, MD, has no relevant conflicts of interest to disclose. The editorial and education staff involved with this journal-based CME activity has no relevant conflicts of interest to disclose.Learning ObjectivesUpon completion of this CME activity, the learner should achieve an understanding of:•The clinical problem of persistent pain symptoms following nerve repair or nerve entrapment release•The potential role of perineural scarring that may prevent favorable surgical outcome•Possible treatment options to minimize (place a barrier to) perineural scarring•Clinical evidence for use of potential autogenous synthetic barriers to perineural scarringDeadline: Each examination purchased in 2018 must be completed by January 31, 2019, to be eligible for CME. A certificate will be issued upon completion of the activity. Estimated time to complete each JHS CME activity is up to one hour.Copyright © 2018 by the American Society for Surgery of the Hand. All rights reserved. The Journal of Hand Surgery will contain at least 2 clinically relevant articles selected by the editor to be offered for CME in each issue. For CME credit, the participant must read the articles in print or online and correctly answer all related questions through an online examination. The questions on the test are designed to make the reader think and will occasionally require the reader to go back and scrutinize the article for details. The JHS CME Activity fee of $15.00 includes the exam questions/answers only and does not include access to the JHS articles referenced. Statement of Need: This CME activity was developed by the JHS editors as a convenient education tool to help increase or affirm reader's knowledge. The overall goal of the activity is for participants to evaluate the appropriateness of clinical data and apply it to their practice and the provision of patient care. Accreditation: The ASSH is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. AMA PRA Credit Designation: The American Society for Surgery of the Hand designates this Journal-Based CME activity for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. ASSH Disclaimer: The material presented in this CME activity is made available by the ASSH for educational purposes only. This material is not intended to represent the only methods or the best procedures appropriate for the medical situation(s) discussed, but rather it is intended to present an approach, view, statement, or opinion of the authors that may be helpful, or of interest, to other practitioners. Examinees agree to participate in this medical education activity, sponsored by the ASSH, with full knowledge and awareness that they waive any claim they may have against the ASSH for reliance on any information presented. The approval of the US Food and Drug Administration is required for procedures and drugs that are considered experimental. Instrumentation systems discussed or reviewed during this educational activity may not yet have received FDA approval. Provider Information can be found at https://www.assh.org/About-ASSH/Contact-Us. Technical Requirements for the Online Examination can be found at https://www.jhandsurg.org/cme/home. Privacy Policy can be found at http://www.assh.org/About-ASSH/Policies/ASSH-Policies. ASSH Disclosure Policy: As a provider accredited by the ACCME, the ASSH must ensure balance, independence, objectivity, and scientific rigor in all its activities. David Netscher, MD, has no relevant conflicts of interest to disclose. All authors of this journal-based CME activity have no relevant conflicts of interest to disclose. In the printed or PDF version of this article, author affiliations can be found at the bottom of the first page. David Netscher, MD, has no relevant conflicts of interest to disclose. The editorial and education staff involved with this journal-based CME activity has no relevant conflicts of interest to disclose. Upon completion of this CME activity, the learner should achieve an understanding of:•The clinical problem of persistent pain symptoms following nerve repair or nerve entrapment release•The potential role of perineural scarring that may prevent favorable surgical outcome•Possible treatment options to minimize (place a barrier to) perineural scarring•Clinical evidence for use of potential autogenous synthetic barriers to perineural scarring Deadline: Each examination purchased in 2018 must be completed by January 31, 2019, to be eligible for CME. A certificate will be issued upon completion of the activity. Estimated time to complete each JHS CME activity is up to one hour. Copyright © 2018 by the American Society for Surgery of the Hand. All rights reserved. We conducted a review of the published literature regarding perineural scarring and barriers. A search was conducted in Ovid Medline (1946–present), Embase (1946–present), Clinical Trials database, Cochrane Databases, Scopus (1823–present), Science Citation Index (1900–present). A total of 8,841 unique citations were filtered to 47 articles based on article titles and abstracts, with 20 articles included here to support our discussion and promote ongoing dialog on this topic. The ideal barrier to perineural scarring should have the following characteristics: (1) minimal or no chance of rejection or inflammatory reaction; (2) sufficient porosity to facilitate diffusion of nutrients without allowing axonal escape; (3) avoidance of scar-induced ischemia; (4) promotion of nerve gliding; (5) minimal or no donor site morbidity; and (6) minimal cost or supply restraints (Table 1).1Isaacs J. McMurtry J. Different nerve grafting and wrapping options in upper extremity surgery.Curr Orthop Pract. 2014; 25: 456-461Crossref Scopus (4) Google ScholarTable 1Comparison of Nerve Barrier Options Based on Ideal Characteristics for a Barrier to Epineural ScarringIdeal CharacteristicsAdipofascial or Muscle FlapVein WrappingHA-CMC Membrane (Seprafilm)Bovine Collagen (Neurawrap, Neuramend)Porcine Small Intestine Submucosa (Axoguard)BiocompatibleYesNonabsorbableYesNonabsorbableNo reports of rejectionAbsorbs by 7 dNo reports of rejectionAbsorbs by 4–8 moNo reports of rejectionAbsorbs by 3 moSemipermeableYesYesYesYesYesNonconstrictingNo reported cases of cicatrix formation after useNo reported cases of cicatrix formation after useNo reported cases of cicatrix formation after useNo reported cases of cicatrix formation after useNo reported cases of cicatrix formation after usePromote nerve glidingYesYes—demonstrated in animal modelUnknownUnknownUnknownMinimal/no donor site morbidityDepends on flap harvested (minimal for local fat pad flap)Yes (typically edema)No donor site morbidityNo donor site morbidityNo donor site morbidityMinimal cost or supply restraintsIncreased surgery timeIncreased surgery timeSubject to implant cost and availabilitySubject to implant cost and availabilitySubject to implant cost and availability Open table in a new tab The concept of using local tissues to provide a barrier around a nerve has been promoted extensively in the treatment of recurrent carpal tunnel syndrome (CTS) and cubital tunnel syndrome (CuTS). Whereas incomplete release of the transverse carpal ligament during carpal tunnel release (CTR) or newly created points of compression of the transposed ulnar nerve are common reasons for revision surgery, another frequent finding during revision surgeries for both CTS and CuTS is adherence of the nerve to the surrounding tissues. Soltani et al2Soltani A.M. Allan B.J. Best M.J. Mir H.S. Panthaki Z.J. A systematic review of the literature on the outcomes of treatment for recurrent and persistent carpal tunnel syndrome.Plast Reconstr Surg. 2013; 132: 114-121Crossref PubMed Scopus (36) Google Scholar performed a systematic review for surgical treatment of recurrent CTS. Of the 14 articles describing rotational or free flap coverage options, 7 discussed hypothenar fat pad or ulnar artery-based perforator flaps.2Soltani A.M. Allan B.J. Best M.J. Mir H.S. Panthaki Z.J. A systematic review of the literature on the outcomes of treatment for recurrent and persistent carpal tunnel syndrome.Plast Reconstr Surg. 2013; 132: 114-121Crossref PubMed Scopus (36) Google Scholar Additional options include other rotational flaps (synovium, pronator quadratus, palmaris brevis, abductor digiti minimi, and radial artery perforator) and free flaps (omentum and anterolateral thigh flaps). Of all options for flap coverage in revision carpal tunnel release, we prefer the hypothenar fat pad flap because of minimal morbidity and reliable blood supply (Fig. 1). In the meta-analysis of 14 studies (n = 294) using flap coverage during revision CTR, there was an 86% success rate. This was substantially higher than the 74% success rate seen in patients treated with decompression alone (7 studies; n = 364). More recently, Pace et al3Pace GI, Zale CL, Gendelberg D, Taylor KF. Self-reported outcomes for patients undergoing revision carpal tunnel surgery with or without hypothenar fat pad transposition [published online ahead of print March 1, 2017]. Hand (N Y). https://doi.org/10.1177/1558944717701243.Google Scholar performed an unmatched, retrospective cohort study of patients who underwent flap interposition or decompression only during revision CTR. The authors did not detect a difference in outcomes, but they did not report a power analysis.3Pace GI, Zale CL, Gendelberg D, Taylor KF. Self-reported outcomes for patients undergoing revision carpal tunnel surgery with or without hypothenar fat pad transposition [published online ahead of print March 1, 2017]. Hand (N Y). https://doi.org/10.1177/1558944717701243.Google Scholar With regard to recurrent CuTS, there is little evidence-based guidance in the literature about the type of procedure to use during revision cases. We have found that perineural fibrosis may form after any of the procedures used for primary treatment. Submuscular transposition provides a reliable gliding surface for the ulnar nerve, provided that new points of compression are not created. The decision about whether to add an additional barrier to scarring around the nerve is described in more detail later. With regard to nerve repairs, we are unaware of any published series dedicated to examining outcomes of flap coverage of repaired nerves alone. Veins provide an ideal surface to place around a nerve after it has been repaired or dissected from scar because it is biologically compatible and vein intima provides a gliding surface (Fig. 2). In a rat sciatic nerve compressive neuropathy model, Xu et al4Xu J. Varitimidis S.E. Fisher K.J. Tomaino M.M. Sotereanos D.G. The effect of wrapping scarred nerves with autogenous vein graft to treat recurrent chronic nerve compression.J Hand Surg Am. 2000; 25: 93-103Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar demonstrated gliding of the vein wrap along the nerve trunk, improvement in electrophysiological testing, and less scarring on histological examination in nerves wrapped with autologous vein compared with controls. Murakami et al5Murakami K. Kuniyoshi K. Iwakura N. et al.Vein wrapping for chronic nerve constriction injury in a rat model: study showing increases in VEGF and HGF production and prevention of pain-associated behaviors and nerve damage.J Bone Joint Surg Am. 2014; 96: 859-867Crossref PubMed Scopus (20) Google Scholar also noted decreased perineural scarring in a rat compressive neuropathy model after vein wrapping. Since the concept was introduced by Masear in 1989 for the treatment of recurrent tarsal tunnel syndrome, there have been numerous case series describing the effectiveness of autologous vein wraps in treatment of recurrent CTS6Sotereanos D.G. Giannakopoulos P.N. Mitsionis G.I. Xu J. Herndon J.H. Vein-graft wrapping for the treatment of recurrent compression of the median nerve.Microsurgery. 1995; 16: 752-756Crossref PubMed Scopus (62) Google Scholar and CuTS.7Kokkalis Z.T. Jain S. Sotereanos D.G. Vein wrapping at cubital tunnel for ulnar nerve problems.J Shoulder Elbow Surg. 2010; 19: 91-97Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar The potential disadvantages of using autologous vein wraps include donor site morbidity (including swelling) as well as increased operative time and technical difficulty if adequate assistance is not available. Promising results with vein allografts have been reported, but availability in the United States is limited. There are no clinical studies comparing patients with compressive neuropathy treated with vein wraps with either control patients or other types of nerve barriers. Regarding nerve repair, there is a single case series describing vein wrapping after nerve repair—Sadek et al8Sadek A.F. Fouly E.H. Hamdy M. Functional and electrophysiological outcome after autogenous vein wrapping of primary repaired ulnar nerves.Microsurgery. 2014; 34 (361–356)Crossref PubMed Scopus (9) Google Scholar reported that patients with saphenous vein wrapping of ulnar nerve repairs had improved motor, sensory, and electrophysiological recovery compared with unmatched historical controls. Many of the commercially available nerve wraps are composed largely of collagen, the main component of the extracellular matrix, and are similar in material composition to nerve conduit products. Type 1 collagen is an appealing material to use as a nerve wrap because it has a long track record of biocompatibility and has selective permeability (Table 2). The biocompatibility of these wraps has been demonstrated in laboratory testing of nerve repair conduits composed of the same material. The most commonly used source for the type 1 collagen wraps is bovine tendon, with a degradation time ranging from 4 to 8 months. There is limited laboratory evidence demonstrating the efficacy or safety of these wraps following nerve repair. In a rat sciatic nerve model, Lee et al9Lee J.Y. Parisi T.J. Friedrich P.F. Bishop A.T. Shin A.Y. Does the addition of a nerve wrap to a motor nerve repair affect motor outcomes?.Microsurgery. 2014; 34: 562-567Crossref PubMed Scopus (30) Google Scholar demonstrated decreased perineural scarring compared with controls, but no difference in axon counts or density. To our knowledge, there are no clinical reports of type 1 collagen wrap use after nerve repair. Although there are no laboratory models of type 1 collagen wrap use in compressive neuropathy, recent clinical series have described use of type 1 collagen wraps after revision CTS cases. Kokkalis et al10Kokkalis Z.T. Mavrogenis A.F. Ballas E.G. Papagelopoulos P.J. Soucacos P.N. Collagen nerve wrap for median nerve scarring.Orthopedics. 2015; 38: 117-121Crossref PubMed Scopus (18) Google Scholar described 2 cases with clinical improvement and no signs of intolerance or complications. In addition, Soltani et al11Soltani A.M. Allan B.J. Best M.J. Mir H.S. Panthaki Z.J. Revision decompression and collagen nerve wrap for recurrent and persistent compression neuropathies of the upper extremity.Ann Plast Surg. 2014; 72: 572-578Crossref PubMed Scopus (41) Google Scholar used a type 1 collagen wrap in 9 recurrent CTS and 6 recurrent CuTS cases; all but 2 patients demonstrated improvement in symptoms. There were no reoperations or signs of collagen wrap intolerance in the series.11Soltani A.M. Allan B.J. Best M.J. Mir H.S. Panthaki Z.J. Revision decompression and collagen nerve wrap for recurrent and persistent compression neuropathies of the upper extremity.Ann Plast Surg. 2014; 72: 572-578Crossref PubMed Scopus (41) Google ScholarTable 2Nerve Wraps That Are Commercially Available in the United StatesProduct Name (Manufacturer)DescriptionLaboratory EvidenceClinical EvidenceAutologous vein wrappingIntimal surface of vein placed along epineurium and wrapped circumferentiallyNerve repair:Rat sciatic nerve—decreased perineural scar compared with controls13Mathieu L. Adam C. Legagneux J. Bruneval P. Masmejean E. Reduction of neural scarring after peripheral nerve suture: an experimental study about collagen membrane and autologous vein wrapping.Chir Main. 2012; 31: 311-317Crossref PubMed Scopus (20) Google ScholarCompressive neuropathy:Rat sciatic nerve—decreased perineural scar, improved electrophysiological testing, larger axons compared with controls4Xu J. Varitimidis S.E. Fisher K.J. Tomaino M.M. Sotereanos D.G. The effect of wrapping scarred nerves with autogenous vein graft to treat recurrent chronic nerve compression.J Hand Surg Am. 2000; 25: 93-103Abstract Full Text Full Text PDF PubMed Scopus (71) Google ScholarNerve repair:1 case series8Sadek A.F. Fouly E.H. Hamdy M. Functional and electrophysiological outcome after autogenous vein wrapping of primary repaired ulnar nerves.Microsurgery. 2014; 34 (361–356)Crossref PubMed Scopus (9) Google ScholarCompressive neuropathy:4 case series6Sotereanos D.G. Giannakopoulos P.N. Mitsionis G.I. Xu J. Herndon J.H. Vein-graft wrapping for the treatment of recurrent compression of the median nerve.Microsurgery. 1995; 16: 752-756Crossref PubMed Scopus (62) Google Scholar, 7Kokkalis Z.T. Jain S. Sotereanos D.G. Vein wrapping at cubital tunnel for ulnar nerve problems.J Shoulder Elbow Surg. 2010; 19: 91-97Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar, 21Schon L.C. Anderson C.D. Easley M.E. et al.Surgical treatment of chronic lower extremity neuropathic pain.Clin Orthop Relat Res. 2001; : 156-164Google Scholar, 22Masear V.R. Nerve wrapping.Foot Ankle Clin. 2011; 16: 327-337Abstract Full Text Full Text PDF PubMed Scopus (22) Google ScholarNeuraWrap (Integra Life Sciences)Bovine-derived type 1 collagenNerve repair:Rat sciatic nerve—decreased perineural scar, no difference in axon counts compared with controls9Lee J.Y. Parisi T.J. Friedrich P.F. Bishop A.T. Shin A.Y. Does the addition of a nerve wrap to a motor nerve repair affect motor outcomes?.Microsurgery. 2014; 34: 562-567Crossref PubMed Scopus (30) Google ScholarCompressive neuropathy:NoneNerve repair:NoneCompressive neuropathy:2 case series10Kokkalis Z.T. Mavrogenis A.F. Ballas E.G. Papagelopoulos P.J. Soucacos P.N. Collagen nerve wrap for median nerve scarring.Orthopedics. 2015; 38: 117-121Crossref PubMed Scopus (18) Google Scholar, 11Soltani A.M. Allan B.J. Best M.J. Mir H.S. Panthaki Z.J. Revision decompression and collagen nerve wrap for recurrent and persistent compression neuropathies of the upper extremity.Ann Plast Surg. 2014; 72: 572-578Crossref PubMed Scopus (41) Google ScholarAxoGuard Nerve Wrap (Axogen)Porcine small intestine submucosaNerve repair:Rat sciatic nerve—more effectively reduced intraneural fibrosis than vein wrapping13Mathieu L. Adam C. Legagneux J. Bruneval P. Masmejean E. Reduction of neural scarring after peripheral nerve suture: an experimental study about collagen membrane and autologous vein wrapping.Chir Main. 2012; 31: 311-317Crossref PubMed Scopus (20) Google ScholarCompressive neuropathy:NoneNerve repair:NoneCompressive neuropathy:1 case series14Papatheodorou L.K. Williams B.G. Sotereanos D.G. Preliminary results of recurrent cubital tunnel syndrome treated with neurolysis and porcine extracellular matrix nerve wrap.J Hand Surg Am. 2015; 40: 987-992Abstract Full Text Full Text PDF PubMed Scopus (30) Google ScholarSeprafilm (Genzyme)Non–FDA-indicatedHA-CMC filmNerve repair:Rat sciatic nerve—decreased adhesions compared with control group17Magill C.K. Tuffaha S.H. Yee A. et al.The short- and long-term effects of Seprafilm on peripheral nerves: a histological and functional study.J Reconstr Microsurg. 2009; 25: 345-354Crossref PubMed Scopus (17) Google ScholarCompressive neuropathy:NoneNerve repair:NoneCompressive neuropathy:NoneXWrap Dry (Applied Biologics)Non–FDA-indicatedHuman amniotic membraneNerve repair:Rabbit ulnar nerve and rat sciatic nerve repair models: less perineural fibrosis and adhesion compared with controls18Ozgenel G.Y. Filiz G. Effects of human amniotic fluid on peripheral nerve scarring and regeneration in rats.J Neurosurg. 2003; 98: 371-377Crossref PubMed Scopus (58) Google ScholarCompressive neuropathy:NoneNerve repair:NoneCompressive neuropathy:1 case series19Gaspar M.P. Abdelfattah H.M. Welch I.W. Vosbikian M.M. Kane P.M. Rekant M.S. Recurrent cubital tunnel syndrome treated with revision neurolysis and amniotic membrane nerve wrapping.J Shoulder Elbow Surg. 2016; 25: 2057-2065Abstract Full Text Full Text PDF PubMed Scopus (19) Google ScholarFDA, U.S. Food and Drug Administration. Open table in a new tab FDA, U.S. Food and Drug Administration. Porcine small intestine submucosa, composed of both types 1 and 3 collagen, has recently been developed for use as both a nerve conduit and a nerve wrap (Table 2). The advantage of this material is that it retains its ability to serve as an extracellular matrix scaffold for the regenerating nerve. Like all xenografts, concerns arise from potential immune response or transmission of infectious disease. Processing techniques have been successful in allowing porcine xenograft implantation without clinically obvious rejection. Pertici et al12Pertici V. Laurin J. Marqueste T. Decherchi P. Comparison of a collagen membrane versus a fibrin sealant after a peroneal nerve section and repair: a functional and histological study.Acta Neurochir (Wien). 2014; 156: 1577-1590Crossref PubMed Scopus (6) Google Scholar circumferentially sutured a porcine-derived nerve wrap around an acutely repaired rat peroneal nerve. There were no differences in functional or histological measures among the repair-only, repair + wrap, and repair + fibrin glue cohorts at final follow-up. Although there was an increased histological grade of inflammatory reaction in the repair + wrap group compared with repair + fibrin glue at 1 month postrepair, no difference was observed at 3 months postrepair. The authors attributed the initial difference to degradation of the wrap, which was complete by 3 months. In the only study that compared 2 different nerve barriers, Mathieu et al13Mathieu L. Adam C. Legagneux J. Bruneval P. Masmejean E. Reduction of neural scarring after peripheral nerve suture: an experimental study about collagen membrane and autologous vein wrapping.Chir Main. 2012; 31: 311-317Crossref PubMed Scopus (20) Google Scholar demonstrated that a porcine-derived nerve wrap more effectively reduced intraneural fibrosis than vein wrapping in a rat sciatic nerve repair model. Although the nerve wrap used by Pertici et al12Pertici V. Laurin J. Marqueste T. Decherchi P. Comparison of a collagen membrane versus a fibrin sealant after a peroneal nerve section and repair: a functional and histological study.Acta Neurochir (Wien). 2014; 156: 1577-1590Crossref PubMed Scopus (6) Google Scholar and Mathieu et al13Mathieu L. Adam C. Legagneux J. Bruneval P. Masmejean E. Reduction of neural scarring after peripheral nerve suture: an experimental study about collagen membrane and autologous vein wrapping.Chir Main. 2012; 31: 311-317Crossref PubMed Scopus (20) Google Scholar is (1) different from the porcine wrap available in the United States and (2) applied in rats, the lessons regarding porcine xenograft biocompatibility may hold value. To our knowledge, there are no clinical reports of porcine-derived nerve wrap use in association with acute nerve repair. Papatheodorou et al14Papatheodorou L.K. Williams B.G. Sotereanos D.G. Preliminary results of recurrent cubital tunnel syndrome treated with neurolysis and porcine extracellular matrix nerve wrap.J Hand Surg Am. 2015; 40: 987-992Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar recently described the use of the porcine wrap in a case series of 12 patients with recurrent CuTS. There were no adverse reactions or complications and all patients had clinical improvement in patient-reported outcomes and grip strength. Although not specifically designed, marketed, or U.S. Food and Drug Administration–indicated for use as a perineural barrier to scarring, hyaluronic acid–carboxymethylcellulose film (HA-CMC) has been examined in both clinical and laboratory studies. Hyaluronic acid is a component of the extracellular membrane and contributes to wound healing and nerve regeneration. Mixing the HA with CMC slows the resorption of the HA, allowing it to exert its effect over a longer period of time (commercially available HA-CMC films typically absorb within 7 days). The benefits of HA-CMC membranes have also been demonstrated in preventing restrictive adhesions in a chicken flexor tendon model15Isik S. Ozturk S. Gurses S. et al.Prevention of restrictive adhesions in primary tendon repair by HA-membrane: experimental research in chickens.Br J Plast Surg. 1999; 52: 373-379Abstract Full Text PDF PubMed Scopus (61) Google Scholar and in reducing the incidence, extent, and severity of postoperative abdominal adhesions.16Kumar S. Wong P.F. Leaper D.J. Intra-peritoneal prophylactic agents for preventing adhesions and adhesive intestinal obstruction after non-gynaecological abdominal surgery.Cochrane Database Syst Rev. 2009; 1CD005080PubMed Google Scholar In a rat sciatic nerve model, Magill et al17Magill C.K. Tuffaha S.H. Yee A. et al.The short- and long-term effects of Seprafilm on peripheral nerves: a histological and functional study.J Reconstr Microsurg. 2009; 25: 345-354Crossref PubMed Scopus (17) Google Scholar noted less perineural scarring on histomorphometric and stereological analyses after a commercially available HA-CMC film (Seprafilm; Genzyme, Cambridge, MA) was wrapped around a rat sciatic nerve after injury and repair relative to a control group. This study also included a noninjury phase in which the HA-CMC film was placed onto, or wrapped around, an intact nerve; no significant differences were found compared with a control group, suggesting that it is biocompatible.17Magill C.K. Tuffaha S.H. Yee A. et al.The short- and long-term effects of Seprafilm on peripheral nerves: a histological and functional study.J Reconstr Microsurg. 2009; 25: 345-354Crossref PubMed Scopus (17) Google Scholar To our knowledge, there are no clinical data in the peer-reviewed literature demonstrating the efficacy of HA-CMC films used for acute nerve repair or chronic compressive neuropathy. Human amniotic membrane wraps have also been described as a barrier to perineural fibrosis. Laboratory studies using human amniotic membrane wraps in a rabbit model demonstrate less perineural fibrosis and adhesion compared to controls.18Ozgenel G.Y. Filiz G. Effects of human amniotic fluid on peripheral nerve scarring and regeneration in rats.J Neurosurg. 2003; 98: 371-377Crossref PubMed Scopus (58) Google Scholar To our knowledge, there are no clinical reports of amnionic membrane wrap use in the nerve injury setting. Gaspar et al19Gaspar M.P. Abdelfattah H.M. Welch I.W. Vosbikian M.M. Kane P.M. Rekant M.S. Recurrent cubital tunnel syndrome treated with revision neurolysis and amniotic membrane nerve wrapping.J Shoulder Elbow Surg. 2016; 25: 2057-2065Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar reported the use of a commercially available amniotic membrane wrap (XWrap Dry; Applied Biologics, Scottsdale, AZ) during 8 revision cubital tunnel cases. There were no signs of adverse reactions or complications reported, and all patients had clinical improvement in patient-reported outcomes and grip strength. However, preliminary results using amniotic wraps placed around repaired flexor tendons demonstrated unfavorable results with inflammatory responses and local fibrosis.20Leppänen O.V. Karjalainen T. Göransson H. et al.Outcomes after flexor tendon repair combined with the application of human amniotic membrane allograft.J Hand Surg Am. 2017; 42: 474.e1-474.e8Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar The U.S. Food and Drug Administration indications for XWrap do not include use as a barrier to nerve adhesion. For recurrent CTS, our preference is to use the hypothenar fat pad flap if intraoperative inspection demonstrates scarring of the median nerve to the surrounding tissue. If the transverse carpal ligament has reconstituted and there is no perineural fibrosis, we perform a decompression only. For CuTS, our preference is to perform a submuscular ulnar nerve transposition (with a very loose approximation of the flexor-pronator fascia) to provide a favorable environment for the ulnar nerve. We apply an autologous vein wrap if a submuscular transposition has already been performed and there is epineural fibrosis on intraoperative inspection. For nerve repairs, we do not routinely use any of the commercially available scar barriers owing to the absence of laboratory or clinical evidence of commercially available barriers for primary nerve repair. If the nerve coaptation will be vulnerable to traction from surrounding structures, we use an autologous vein wrap or local/rotational soft tissue flap for coverage. This publication was made possible by Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448, subaward KL2 TR000450 (C.J.D.) from the NIH-National Center for Advancing Translational Sciences (NCATS), components of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. This publication's contents are solely the responsibility of the authors and do not necessarily represent the official view of NCATS or NIH. Download .xml (.0 MB) Help with xml files Data Profile Journal CME QuestionsJournal of Hand SurgeryVol. 43Issue 4Preview Full-Text PDF