Prospective Multicentre Registry of High-Purity Type I Collagen Nerve Wrapping in Peripheral Nerve Procedures: Early Clinical Outcomes
Phase: NA
Conditions: Peripheral Nerve Injuries, Neuroma of Nerve Repair, Nerve Graft; Complications, Mechanical, Peripheral Nerve Decompression Injury, Neuroma
Sponsor: Adichunchanagiri Institute of Medical Sciences, B G Nagara

Title: High-Purity Type I Collagen Nerve Wrapping in Peripheral Nerve 
Procedures: A Prospective Registry 
 
NCT No: NCT07360730 
 
Date: March 05, 2026 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

INTRODUCTION 
Peripheral nerve injuries and compressive neuropathies constitute a significant cause of long-
term functional impairment, chronic pain, and disability worldwide. Despite substantial 
advances in microsurgical techniques, including tension-free nerve repair, refined coaptation 
methods, and improved magnification, functional recovery following peripheral nerve 
surgery remains highly variable and often suboptimal, particularly in complex clinical 
scenarios such as delayed repairs, revision decompressions, nerve grafting, and nerve 
transfers [1,2]. The disparity between technical success and functional recovery underscores 
the importance of biological factors that govern nerve healing beyond surgical precision 
alone. 
One of the principal biological impediments to successful nerve regeneration is perineural 
fibrosis, which develops as part of the normal wound-healing response following nerve injury 
or surgical manipulation. Excessive fibroblast proliferation and disorganized collagen 
deposition within the perineural environment result in circumferential scarring that restricts 
nerve gliding, compromises intraneural microcirculation, and alters axonal regeneration 
dynamics [3,4]. This fibrotic tethering not only limits functional recovery but is also strongly 
associated with persistent neuropathic pain and recurrent symptoms following nerve 
decompression procedures [5,6]. 
The pathophysiology of impaired nerve regeneration is multifactorial and involves a complex 
interplay between Schwann cell activity, axonal sprouting, angiogenesis, extracellular matrix 
(ECM) remodelling, and inflammatory modulation [7]. While Schwann cells play a central 
role in guiding axonal regrowth and remyelination, their function is highly dependent on the 
surrounding ECM architecture and mechanical environment [8]. Disruption of this 
microenvironment by dense scar tissue interferes with axonal guidance, delays remyelination, 
and increases susceptibility to conduction block and neuroma formation [9]. 
To address these challenges, various strategies have been explored to modulate the perineural 
healing environment, including vein wrapping, adipofascial flaps, synthetic nerve wraps, and 
barrier membranes [10–12]. Although these techniques may reduce adhesion formation, their 
widespread adoption has been limited by factors such as donor-site morbidity, inconsistent 
availability, foreign body reactions, inflammatory responses, and unpredictable degradation 
profiles [13,14]. Consequently, there has been growing interest in biologically derived, 
resorbable materials that combine mechanical barrier function with active biological support 
for nerve regeneration. 

High-purity type I collagen (HPTC) represents a novel class of bioengineered collagen-based 
biomaterials designed to function not merely as passive barriers but as biologically active 
scaffolds that support organized tissue regeneration. Type I collagen is the predominant 
structural protein of native ECM and plays a critical role in cellular adhesion, migration, 
angiogenesis, and matrix remodelling during tissue repair [15,16]. When processed to high 
purity with removal of antigenic components, collagen matrices demonstrate excellent 
biocompatibility, controlled biodegradation, and minimal immunogenicity [17]. 
HPTC (Surgicoll-Mesh®) is an acellular, high-purity (>97%) type I collagen membrane 
manufactured through a proprietary purification process that preserves the native triple-
helical collagen structure while eliminating inflammatory and antigenic residues [18]. This 
structural integrity enables HPTC to closely mimic native ECM, providing an optimal 
scaffold for Schwann cell alignment, axonal guidance, and neovascularization. Unlike 
synthetic materials, HPTC undergoes gradual enzymatic degradation, allowing progressive 
replacement by organized host tissue rather than dense scar formation [19]. 
The regenerative potential of HPTC has been demonstrated across multiple clinical contexts. 
Randomized controlled trials and prospective studies have shown that HPTC significantly 
improves healing rates, tissue quality, and functional outcomes in diabetic foot ulcers, venous 
leg ulcers, pressure ulcers, and complex reconstructive applications [18–22]. Notably, several 
studies by the present authors have consistently demonstrated the anti-fibrotic, pro-
angiogenic, and regenerative properties of HPTC in breast reconstruction, peritoneal repair, 
Z-plasty scar modulation, and full-thickness wound management, with reproducible clinical 
benefit across diverse tissue environments [20–24]. 
Despite this growing body of evidence, the application of HPTC as a circumferential nerve 
wrap in peripheral nerve surgery remains relatively underexplored. The theoretical rationale 
for its use in nerve surgery is compelling. By providing a temporary, resorbable perineural 
barrier, HPTC may reduce adhesion formation and mechanical tethering, while its 
biologically active collagen scaffold may facilitate Schwann cell migration, promote 
angiogenesis, and support organized axonal regeneration [25–27]. Importantly, such an 
approach addresses both the mechanical and biological determinants of nerve healing. 
Electrophysiological recovery, as assessed by nerve conduction velocity (NCV) and 
electromyography (EMG), offers an objective and sensitive means of evaluating early axonal 
regeneration and remyelination, often preceding overt clinical recovery [28,29]. 
Improvements in NCV reflect restoration of myelin integrity and axonal maturation, while 
EMG provides insight into motor unit recruitment and reinnervation patterns. The 

incorporation of electrophysiological endpoints is therefore critical for validating the 
biological efficacy of regenerative adjuncts such as HPTC. 
The present prospective multicentre registry was designed to generate real-world evidence on 
the safety, feasibility, and early outcomes of HPTC nerve wrapping across a broad spectrum 
of peripheral nerve procedures. By integrating clinical, patient-reported, and 
electrophysiological endpoints, this study aims to provide a comprehensive evaluation of 
HPTC as a biologically effective adjunct in peripheral nerve surgery. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

MATERIALS AND METHODS 
Study Design and Setting 
This study was conducted as a prospective, multicentre, observational registry designed to 
evaluate early clinical, functional, and electrophysiological outcomes following the use of 
high-purity type I collagen (HPTC) nerve wrapping in peripheral nerve surgery. The registry 
was implemented across two tertiary referral centres in India – Adichunchangiri Institute of 
Medical Sciences, B G Nagara and Mysore Medical College and Research Institute, Mysuru. 
The study was conceived as a real-world outcomes’ registry rather than a randomized 
controlled trial, with the objective of capturing effectiveness, safety, and biological response 
in routine clinical practice. The trial was registered prospectively with ClinicalTrials.gov (ID: 
NCT07360730) and approved by the Institutional Ethics Committee (Approval No.: 
AIMS/IEC/269/2025). 
The study was conducted in accordance with the principles of the Declaration of Helsinki and 
Good Clinical Practice guidelines. Institutional Ethics Committee approval was obtained at 
each participating centre prior to initiation of patient recruitment. Written informed consent 
was obtained from all participants after detailed explanation of the study objectives, 
procedures, risks, and benefits. 
 
Patient Selection 
Adult patients aged 18 to 70 years undergoing peripheral nerve surgery were screened for 
inclusion. Eligible procedures included primary nerve repair, nerve coaptation, nerve 
grafting, nerve transfer, and primary or revision nerve decompression involving upper or 
lower limb peripheral nerves. Inclusion required the intraoperative use of HPTC as a 
circumferential nerve wrap following completion of the primary nerve procedure. 
Exclusion criteria included active infection at the operative site, known hypersensitivity to 
collagen or bovine-derived products, pregnancy or lactation, severe uncontrolled systemic 
illness, immunosuppressive therapy, malignancy involving the nerve or surrounding tissue, 
and re-operation at the same nerve site within the preceding six months. Patients unable to 
comply with postoperative rehabilitation or follow-up assessments were also excluded. 
 
Surgical Technique and Application of HPTC 
All procedures were performed under loupe or operating microscope magnification by 
experienced peripheral nerve surgeons. Following completion of the primary nerve 

procedure, meticulous haemostasis was achieved to minimize postoperative inflammation and 
scar formation. Care was taken to avoid excessive manipulation of the nerve and surrounding 
tissues. 
A sterile HPTC (Surgicoll-Mesh®) [30] was hydrated in normal saline according to 
manufacturer instructions. The membrane was trimmed to correspond to the length of the 
repaired, grafted, transferred, or decompressed nerve segment, typically ranging from 1.5 to 
4.0 cm. The HPTC sheet was then applied circumferentially around the nerve as a loose 
perineural sleeve, ensuring that the wrap did not exert compressive forces or restrict 
physiological nerve excursion. 
Fixation was achieved using fibrin glue or fine absorbable sutures placed sparingly at the 
edges of the wrap. Particular attention was paid to maintaining a non-constrictive 
configuration to preserve intraneural microcirculation and facilitate postoperative nerve 
gliding (Figure 1-3).  
Standard wound closure was performed in layers, and all patients followed institution-
specific postoperative rehabilitation protocols tailored to the type of nerve procedure 
performed. 
Figure 1. Neuroma-in-continuity excision and interposition cable sural nerve grafting 
with HPTC nerve wrap 
 
Intraoperative sequence demonstrating neuroma-in-continuity of median nerve. The 
pathological neuroma segment was excised to healthy fascicular ends, followed by 
reconstruction using multiple cable sural nerve grafts to bridge the defect. The proximal and 
distal coaptation sites and grafted segment were circumferentially wrapped with a hydrated 
high-purity type I collagen (HPTC) membrane applied as a loose, non-constrictive perineural 
sleeve to provide a biologic anti-adhesion barrier and regenerative scaffold prior to wound 
closure. 

Figure 2: Traumatic median nerve repair with collagen nerve wrap augmentation 
 
Intraoperative images of a traumatic median nerve injury. Following debridement and 
tension-free epineurial coaptation, the repair site was covered with a hydrated high-purity 
type I collagen (HPTC) sheet circumferentially wrapped around the coaptation zone. The 
collagen wrap was secured in a loose configuration to avoid compression while isolating the 
repair from surrounding tissues to reduce perineural fibrosis and support organized 
regeneration. 
 
Figure 3: Brachial plexus nerve transfer with HPTC-protected coaptation 
 
Nerve transfer for brachial plexus injury. After donor-to-recipient nerve coaptation, the 
neurorrhaphy sites were covered with hydrated high-purity type I collagen (HPTC) 
membranes placed circumferentially over each coaptation zone. The collagen scaffold was 
applied as a protective biologic sleeve to minimize scar adherence and facilitate axonal 
regeneration within the plexus bed prior to layered closure. 
 

Outcome Measures 
The primary outcome of the study was motor recovery assessed using the Medical Research 
Council (MRC) grading system at six months postoperatively. Successful motor recovery was 
predefined as achievement of MRC grade M3 or higher, reflecting antigravity muscle 
function with active movement. 
Secondary outcomes included sensory recovery assessed using static and moving two-point 
discrimination and Semmes–Weinstein monofilament testing, neuropathic pain evaluated 
using the Visual Analog Scale (VAS), patient-reported functional outcomes measured using 
the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire for upper 
limb nerves and the Lower Extremity Functional Scale (LEFS) for lower limb nerves, 
electrophysiological recovery assessed by nerve conduction velocity (NCV) and 
electromyography (EMG), and incidence of postoperative complications. 
 
Electrophysiological Assessment Protocol 
Electrophysiological evaluation was incorporated as a predefined secondary outcome to 
provide objective evidence of axonal regeneration and remyelination. Standardized nerve 
conduction studies and needle electromyography were performed at baseline, two months, 
and four months postoperatively by experienced neurophysiologists blinded to procedural 
type and clinical outcomes [31,32]. 
Nerve conduction velocity was measured across the involved nerve segment using surface 
electrodes placed proximal and distal to the surgical site. Standardized stimulation parameters 
were used to record compound muscle action potentials, and NCV was calculated in meters 
per second. Improvements in NCV were interpreted as indicative of remyelination and axonal 
maturation [33]. 
Needle electromyography was performed in muscles innervated by the treated nerve to assess 
spontaneous activity, motor unit potential morphology, and recruitment patterns. A composite 
reinnervation score on a standardized five-point scale was used, incorporating reduction in 
fibrillation potentials, emergence of polyphasic motor unit potentials, and improvement in 
recruitment. EMG changes were interpreted as evidence of axonal continuity and motor unit 
reinnervation [34]. 
 
Sample Size 
The target enrolment of 40 patients was based on a pragmatic feasibility estimate for a 
multicentre registry. Assuming a historical recovery rate of 65% and a minimum detectable 

difference of 20 percentage points at 85% power with a two-sided α of 0.05, a minimum of 
37 patients was required, yielding a planned enrolment of 40 patients to account for potential 
attrition. 
 
Data Collection and Follow-Up 
Baseline demographic data, comorbidities, nerve type, procedure performed, and operative 
details were recorded prospectively. Clinical assessments were conducted at regular 
postoperative intervals, including one month, three months, and six months. 
Electrophysiological assessments were performed at two and four months to capture early 
biological recovery preceding overt clinical improvement. 
Pain scores and patient-reported outcome measures were collected using validated 
instruments administered by trained personnel. All data were recorded in standardized case 
report forms and entered into a secure registry database with predefined quality checks. 
 
Statistical Analysis Plan 
Statistical analyses were performed using IBM SPSS Statistics version 29.0 (IBM Corp., 
Armonk, NY, USA) and R version 4.3.2 (R Foundation for Statistical Computing, Vienna, 
Austria). The statistical analysis plan was defined a priori. All enrolled patients who received 
HPTC nerve wrapping were included in the analysis. Continuous variables were expressed as 
mean ± standard deviation, while categorical variables were expressed as frequencies and 
percentages. The primary outcome proportion of patients achieving MRC grade ≥ M3 at six 
months was compared against historical recovery benchmarks reported in the literature using 
a one-sample proportion Z-test [35]. Ninety-five percent confidence intervals were calculated 
for the observed proportion. Longitudinal changes in pain scores, electrophysiological 
parameters, and functional outcomes were analyzed using repeated-measures analysis of 
variance or equivalent non-parametric tests where appropriate [36]. Paired t-tests were used 
to assess within-patient changes between baseline and follow-up time points. Effect sizes 
were calculated using Cohen’s h for proportions, Cohen’s d for continuous outcomes, and 
partial eta-squared for repeated-measures analyses to quantify the magnitude of observed 
effects independent of sample size [37]. All statistical tests were two-sided, and a p-value of 
less than 0.05 was considered statistically significant. Statistical analyses were performed 
using standard statistical software packages commonly employed in clinical research. 
 
 

REFERENCES 
1. Taylor CA, Braza D, Rice JB, Dillingham T. The incidence of peripheral nerve injury in 
extremity trauma. Am J Phys Med Rehabil. 2008;87(5):381-385. 
doi:10.1097/PHM.0b013e31815e6370 
2. Kim DH, Kline DG. Management and results of peroneal nerve lesions. Neurosurgery. 
1996 Aug;39(2):312-9; discussion 319-20. doi: 10.1097/00006123-199608000-00014. 
3. Lundborg G. Richard P. Bunge memorial lecture. Nerve injury and repair--a challenge to 
the plastic brain. J Peripher Nerv Syst. 2003 Dec;8(4):209-26. doi: 10.1111/j.1085-
9489.2003.03027.x.  
4. Millesi H. The nerve gap. Theory and clinical practice. Hand Clin. 1986;2(4):651-663. 
5. Mobbs RJ, Vonau M, Blum P. Treatment of painful peripheral neuroma by vein 
implantation. J Clin Neurosci. 2003 May;10(3):338-9. doi: 10.1016/s0967-
5868(03)00010-9. PMID: 12763341. 
6. Mackinnon SE, Dellon AL. Surgery of the peripheral nerve. New York: Thieme; 1988. 
7. Gordon T. The role of neurotrophic factors in nerve regeneration. Neurosurg Focus. 2009 
Feb;26(2):E3. doi: 10.3171/FOC.2009.26.2.E3. 
8. Jessen KR, Mirsky R. The repair Schwann cell and its function in regenerating nerves. J 
Physiol. 2016 Jul 1;594(13):3521-31. doi: 10.1113/JP270874. Epub 2016 Mar 21. 
9. Siemionow M, Brzezicki G. Chapter 8: Current techniques and concepts in peripheral 
nerve repair. Int Rev Neurobiol. 2009;87:141-72. doi: 10.1016/S0074-7742(09)87008-6. 
10. Masear VR, Colgin S. The treatment of epineural scarring with allograft vein wrapping. 
Hand Clin. 1996 Nov;12(4):773-9. 
11. Kokkalis ZT, Mavrogenis AF, Ballas EG, Papagelopoulos PJ, Soucacos PN. Collagen 
nerve wrap for median nerve scarring. Orthopedics. 2015 Feb;38(2):117-21. doi: 
10.3928/01477447-20150204-04. 
12. Koh SJQ, Kumar AA, Hwang PYK. Wrap technique for idiopathic trigeminal neuralgia: 
patient series. J Neurosurg Case Lessons. 2025 Aug 18;10(7):CASE25348. doi: 
10.3171/CASE25348. 
13. Sulaiman OA, Gordon T. Effects of short- and long-term Schwann cell denervation on 
peripheral nerve regeneration, myelination, and size. Glia. 2000 Dec;32(3):234-46. doi: 
10.1002/1098-1136(200012)32:3<234::aid-glia40>3.0.co;2-3. 
14. Kehoe S, Zhang XF, Boyd D. FDA approved guidance conduits and wraps for peripheral 
nerve injury: a review of materials and efficacy. Injury. 2012 May;43(5):553-72. doi: 
10.1016/j.injury.2010.12.030. 

15. Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci. 2010 
Dec 15;123(Pt 24):4195-200. doi: 10.1242/jcs.023820. 
16. Shoulders MD, Raines RT. Collagen structure and stability. Annu Rev Biochem. 
2009;78:929-58. doi: 10.1146/annurev.biochem.77.032207.120833. 
17. Zeugolis DI, Paul GR, Attenburrow G. Cross-linking of extruded collagen fibers--a 
biomimetic three-dimensional scaffold for tissue engineering applications. J Biomed 
Mater Res A. 2009 Jun 15;89(4):895-908. doi: 10.1002/jbm.a.32031. 
18. Narayan N, Raghupathi D, Ramamurthy V, Chethan S, Gowda S. A Comparative 
Analysis in the Treatment of Full-Thickness Wounds: Negative-Pressure Wound Therapy 
(NPWT) Combined With High-Purity Type I Collagen-Based Skin Substitute Versus 
NPWT Alone. Cureus. 2025 Nov 16;17(11):e96977. doi: 10.7759/cureus.96977. 
19. Narayan N, Gowda S, Shivannaiah C. A Randomized Controlled Clinical Trial 
Comparing the Use of High Purity Type-I Collagen-Based Skin Substitute vs. Dehydrated 
Human Amnion/Chorion Membrane in the Treatment of Diabetic Foot Ulcers. Cureus. 
2024 Dec 5;16(12):e75182. doi: 10.7759/cureus.75182. 
20. Narayan N, Shivannaiah C, Gowda S. Evaluating the Efficacy of High-Purity Type I 
Collagen-Based Skin Substitute Versus Dehydrated Human Amnion/Chorion Membrane 
in the Treatment of Venous Leg Ulcers: A Randomized Controlled Clinical Trial. Cureus. 
2025 Jul 30;17(7):e89031. doi: 10.7759/cureus.89031. 
21. Dhanraj P, Naveen N, Babu KR, Mahesh MS, Hanumanthaiah KS: Healicoll—an 
alternate to flap cover for bare bones and tendons. Acta Med Int. 2016, 3:146-150. 
10.5530/ami.2016.1.30 
22. Narayan N, Ramegowda YH, Raghupathi DS, et al.: Biological skin substitutes in 
pressure ulcers: high-purity type I collagen-based versus amnion/chorion membrane. 
Cureus. 2025, 17:90956. 10.7759/cureus.90956 
23. Narayan N, Shivaiah R, Kumar V, Kumar KM, Chethan S, Gowda S: Comparative 
efficacy of high purity type I collagen-based skin substitute and dehydrated human 
amnion/chorion membrane in diabetic foot ulcers: A multicentre randomized controlled 
trial. Cureus. 2025, 17:94952. 10.7759/cureus.94952 
24. Narayan N, Nareddula U, Nanjundaiah R K, Manakchand K K: Clinical and 
Histopathological Outcomes of High-Purity Type I Collagen in Chronic Wounds: A 
Systematic Review of Four Randomized Controlled Trials. Cureus. 2025, 17:96977. 
10.7759/cureus.100717 

25. Dahlin LB. Techniques of peripheral nerve repair. Scand J Surg. 2008;97(4):310-6. doi: 
10.1177/145749690809700407. 
26. Brushart TM. Nerve Repair. Oxford: Oxford University Press; 2011. 
27. Hall S. Axonal regeneration through acellular muscle grafts. J Anat. 1997 Jan;190 ( Pt 
1)(Pt 1):57-71. doi: 10.1046/j.1469-7580.1997.19010057.x. 
28. Dumitru D, Amato AA, Zwarts MJ. Electrodiagnostic medicine. 2nd ed. Philadelphia: 
Hanley & Belfus; 2002. 
29. Kimura J. Electrodiagnosis in diseases of nerve and muscle. 4th ed. Oxford: Oxford 
University Press; 2013. 
30. Advanced Biotech Products (P) Ltd. Surgicoll-Mesh®: implantable, bioresorbable tissue 
regenerative sterile type I collagen matrix [product information]. Chennai, India: 
Advanced Biotech Products; 2024. Available from: https://www.advanced-
biotech.com/surgicoll-mesh.html 
31. Chung T, Prasad K, Lloyd TE. Peripheral neuropathy: clinical and electrophysiological 
considerations. Neuroimaging Clin N Am. 2014 Feb;24(1):49-65. doi: 
10.1016/j.nic.2013.03.023. 
32. Giacomini PS. Electromyography and Neuromuscular Disorders: Clinical 
Electrophysiologic Correlations. Mcgill J Med. 2006 Jul;9(2):173. 
33. Gordon T, Tyreman N, Raji MA. The basis for diminished functional recovery after 
delayed peripheral nerve repair. J Neurosci. 2011 Apr 6;31(14):5325-34. doi: 
10.1523/JNEUROSCI.6156-10.2011.  
34. Faroni A, Mobasseri SA, Kingham PJ, Reid AJ. Peripheral nerve regeneration: 
experimental strategies and future perspectives. Adv Drug Deliv Rev. 2015 Mar;82-
83:160-7. doi: 10.1016/j.addr.2014.11.010. 
35. Newcombe RG. Two-sided confidence intervals for the single proportion: comparison of 
seven methods. Stat Med. 1998 Apr 30;17(8):857-72. doi: 10.1002/(sici)1097-
0258(19980430)17:8<857::aid-sim777>3.0.co;2-e. 
36. Girden ER. ANOVA: Repeated measures. Sage Publications; 1992. 
37. Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale, NJ: 
Lawrence Erlbaum; 1988.