RemplirTM evidence compendium
This compendium brings together our clinical research and scientific evidence to support informed decision-making. It highlights key studies, findings, and insights, providing a clear and concise reference for healthcare professionals seeking reliable, evidence-based information.
Clinical Paper Summary
Reconstruction of Upper Extremity Peripheral Nerve Injuries Using an Epineurial-Like Collagen Device – A Prospective Clinical Study
Study objective:
An Australian case series study was conducted to evaluate outcomes of nerve reconstruction using Remplir in patients with injuries to the spinal cord, brachial plexus or upper extremity peripheral nerves.
Study population:
A total of 36 peripheral nerve reconstructions were performed in 19 patients aged between 18 and 50 years. Patients in the clinical trial suffered traumatic nerve injuries following motor vehicle, sporting and/or work-related incidents, resulting in partial or total loss of use of their arms and, in more severe cases, their legs and torso as well (tetraplegia). Patients experienced significant pain and were unable to perform basic activities of daily living (i.e. eating, bathing, dressing and toileting), play sport and/or work. Without surgery they would not have regained normal use of their injured arm and hand.
We are now seeing a consistent return of arm and hand function following nerve transfer surgery with Remplir… Remplir is increasing the success rate and efficiency of nerve transfer surgery
Dr Alex O’Beirne
A leading Australian orthopaedic nerve specialist and clinical trial lead
Study results:
Patients received one or more nerve repairs (nerve transfer or nerve graft) augmented with Remplir. Recovery after treatment was assessed by grading the strength of target muscles closest to the site of nerve repair. Outcome data at 12 months post-treatment was available for 16 of 19 patients and 33 nerve repairs (Figure 1). Functional recovery of muscles controlled by the repaired nerve was observed in 76% (25 of 33) repairs at 12 months post-treatment and in 85% (23 of 27) of nerve repairs at 24 months post-treatment. The results demonstrate that functional gains were not only maintained but continued to improve between 12-and 24-months post-treatment.
Figure 1: Patients regained voluntary muscle movement within 12 months increasing strength and range of motion at 24 months.
Grade M3 and M4 – voluntary movement with improved strength and range of motion. Maximum level of recovery expected.
Grade M2 – voluntary movement restored, limited strength and range of movement.
Grade M0 or M1 – no voluntary movement.
Final Results:
85%
(23 of 27)
of nerve repairs resulted in functional recovery of muscles controlled by the repaired nerve at the 24-month post-treatment assessment
White Paper
A Comparative Study of Collagen Nerve Wraps in Peripheral Nerve Repair – Preclinical Rat Sciatic Nerve Transection Model
Data presented at the 2025 IFSSH and IFSHT Triennial Congress in Washington, D.C. M.H. Zheng, E. Landao-Bassonga, C. Lee, T.S Cheng, R. Oliver, M. Lloyd, D. Wills, W.R. Walsh
Introduction:
Surgical repair of transected nerve is essential to restore continuity, however the outcomes from suture only repair are often suboptimal.1 Nerve wrap devices are commonly used to prevent connective tissue invasion and provide a protective environment for optimal nerve healing and regeneration.
This study evaluated the safety and biological performance of Orthocell’s RemplirTM Nerve Wrap (porcine collagen) in comparison to a similar marketed nerve repair device (crosslinked bovine collagen nerve wrap comparator) in a rat sciatic nerve transection model.
Methods:
Rat sciatic nerves were transected and immediately repaired with two epineural sutures reconnecting the proximal and distal ends. A collagen device (Remplir or Comparator) was wrapped around the repair site and fixed in place with an epineurial suture at each end, or the repair site was left unwrapped (Suture only control). Gross anatomical, histological and immunohistochemical assessment of biocompatibility and nerve regeneration was performed at 4-, 12- and 24-weeks post-treatment.
Key Results:
1. No adverse tissue reactions
No evidence of systemic or local toxicity, nor abnormal inflammation or scarring was observed after implantation of Remplir. Macroscopic observation of the implant site showed significant resorption and integration of Remplir at 12 weeks with complete host tissue integration by 24 weeks post-repair (Figure 1). No chronic inflammation, foreign body reaction or fibrosis, and minimal adhesions to surrounding soft tissue, were observed with the use of Remplir. In contrast, the Comparator device was largely intact at 4- and 12-weeks with only microscopic signs of resorption evident at 24 weeks post-repair. The use of the Comparator device was associated with noticeable and progressive increase in adhesions to surrounding tissues over the study period (Figure 1). Localized hematomas, and perineurial fibrosis and encapsulation leading to nerve constriction indicative of foreign body response were oft en observed in Comparator-assisted repairs (Figure 2). Axonal escape and neuroma formation were noted in Suture-only controls.
Remplir conforms to host tissue to protect transected nerve with no adverse reactions and minimal soft tissue adhesion. Device resorption and integration with host epineural tissue observed.
Comparator device largely intact with noticeable adhesion and tethering to surrounding soft tissue and no observable resorption or host tissue integration.
Remplir visibly resorbed and integrated into host epineurial tissue. Tissue appearance similar to Suture-only controls.
Comparator device remains largely intact with minimal resorption and adhering to surrounding soft tissue surrounding soft tissue.
Remplir completely resorbed and integrated into host epineurial tissue with near native-like tissue appearance.
Comparator device still intact with partial resorption but significant adhesion to surrounding soft tissue.
Figure 1: Remplir resorbs and integrates into host epineurial tissue with no adverse reactions. Representative examples of gross observations of Suture only, Remplir-assisted, and Comparator-assisted repairs at 4-, 12-, and 24-weeks post-repair.
Hematoma, signs of hemorrhage, and nerve compression were oft en observed in Comparator-assisted repairs indicative of local irritation and inflammation.
Figure 2: Comparator-assisted repairs exhibited adverse tissue responses consistent with foreign body reactions including formation of local hematoma and progressive fibrotic encapsulation leading to nerve constriction across the repair site.
2. Resorption and integration into host tissue
Early resorption and integration of Remplir into host epineurial tissue, which could facilitate axon regeneration during early healing, was observed after 4 weeks (Figure 3). By 12 weeks post-repair, Remplir had substantially resorbed and integrated into epineurial-like tissue, with complete resorption and integration into host epineurial tissue observed at 24 weeks. Normal physiological inflammation, consistent with healing processes was observed across the observation period. No multinucleated giant cells or other signs of foreign body response to Remplir were observed. In contrast, the Comparator device appeared to remain intact throughout the observation period, encapsulating the nerve with minimal evidence of resorption or integration with host epineurial tissue (Figure 3). Significant inflammation with presence of multinucleated giant cells was observed within the device’s collagen matrix and at the device-nerve interface.
Remplir resorbs and integrates with host tissue to protect transected nerve. No signs of encapsulation.
Comparator device is largely intact with minimal resorption and integration into host tissue.
Remplir largely resorbed and intergrated into epineurium-like tissue (ELT).
Comparator device remains intact and encapsulates nerve with minimal integration into host tissue.
Remplir completely resorbed and fully integrated into epineurium-like tissue.
Comparator device remains visibly intact with some degree of resorption but minimal host tissue integration.
Figure 3: Resorption and integration of Remplir into host epineurial tissue. Representative H&E-stained longitudinal sections of device resorption and host tissue integration at 4-, 12-, and 24-weeks post-repair.
3. Regeneration of high-quality nerve tissue
Neurofilaments are parallel bundles of dense fibres that act as internal scaffolding, providing mechanical stability and maintaining optimal axonal calibre for signal conduction. After peripheral nerve injury, neurofilaments are broken down and cleared during the process of Wallerian degeneration in the distal nerve stump. Neurofilament staining 12 weeks post-treatment revealed Remplir-assisted repairs had the most continuous and longitudinally aligned axonal regeneration across the transection site, closely approximating the organization seen in normal nerve (Figure 4). In contrast, both Suture-only and Comparator-assisted repairs exhibited marked disorganization at the transection site, including misalignment and fragmentation of neurofilament bundles, indicative of axonal misdirection and potential neuroma formation (Figure 4 and Figure 5).
The use of Remplir facilitates superior axonal continuity from proximal to distal segments with robust axonal bridging across the transection site that can lead to faster restoration of electrophysiological signaling and a higher likelihood of functional recovery.
Figure 4: Remplir-assisted repairs facilitate superior axonal continuity from proximal to distal segments with robust axonal bridging across the transection site. Representative neurofilament-stained longitudinal nerve sections showing the proximal, central repair, and distal region of regenerated nerve tissue from Suture-only, Remplir-assisted, and Comparator-assisted repairs at 12-weeks post-repair.
Figure 5: Neurofilament ingrowth and axonal misdirection into fibrogranulation tissue (FG) adjacent to nerve and implanted Comparator device indicating potential neuroma formation. Arrow head indicates suture material.
Toluidine-stained cross-sections of the distal nerve segment at 4-weeks post-repair showed that Remplir-assisted repairs supports earlier axonal regeneration and remyelination compared with Suture-only and Comparator-assisted repairs. The distal nerve segments of Remplir-assisted repairs exhibited greater density of small myelinated axonal profiles indicating earlier axonal sprouting and onset of remyelination (Figure 6). This early regenerative trend in Remplir-assisted repair is inline with the superior neurofilament organization observed in Remplir-assisted repairs at 12-weeks. In contrast, both Suture-only and Comparator-assisted repairs shows irregular and fewer myelinated axons.
Figure 6: Remplir-assisted repairs facilitates early distal axonal sprouting and axon remyelination. Representative images of toluidine blue-stained cross-sections showing the distal nerve segment of regenerated nerve tissue from Suture-only, Remplir-assisted, and Comparator-assisted repairs at 4-weeks post-repair.
Quantitative morphometric analysis of distal nerve segments from 4-24 weeks showed that Remplir-assisted repairs showed favourable regenerative features, with trends towards increased distal axon density and myelinated axon density, and comparatively improved distal:proximal myelination profile (Figure 7).
Together, these findings reinforce Remplir’s ability to support effective axonal bridging, regeneration and maturation. Repairs using the comparator device showed poor distal regeneration due to axonal misalignment and misdirection, while Suture-only repair achieved intermediate but suboptimal results.
Figure 7: Remplir-assisted repairs support a more favourable regenerative profile. Quantitative morphometric assessment of distal axon density, myelinated axon density, and % myelinated axons (distal:proximal) at 4-, 12-, and 24-week post-repair.
4. Supports a more favourable M2 macrophage regenerative environment
Macrophages play important and well-orchestrated roles in peripheral nerve repair. Early pro-inflammatory M1 macrophage presence is necessary for debris clearance and activation of repair programs. Timely switch (polarization) from M1 to pro-regenerative M2 macrophage supports angiogenesis, Schwann cell activity and axonal guidance, and extracellular matrix remodeling. Prolonged M1 macrophage activity or delayed switch to the M2 macrophage response leads to chronic inflammation and fibrosis that can hinder axonal regeneration2.
Remplir supports the most effective M1 (pro-inflammatory) to M2 (pro-regenerative) transition, with early pro-regenerative M2 macrophage activity sustained through the critical regeneration window (weeks 4 to week 12) (Figure 8). The Comparator device shows persistent pro-inflammatory M1 macrophage dominance and weak pro-regenerative M2 response, consistent with its inferior histological and morphometric outcomes (Figure 8).
Figure 8: Remplir-assisted repairs demonstrated a trend towards an accelerated shift from pro-inflammatory M1 to pro-regenerative M2 macrophage profile indicating a comparatively more favourable immune environment for regeneration than Suture-only and Comparator-assisted repairs. Bar charts of M1 and M2 macrophage counts at 4-, 12-, and 24-weeks following surgical repair with Suture-only, Remplir-assisted repair, or Comparator-assisted repair.
5. Return of motor and mechanosensory function
Over the 24-week sensorimotor testing period, Remplir-assisted repairs were associated with earlier and greater restoration of motor function (Extensor Postural Thrust Force) and a generally more favourable trajectory of mechanosensory recovery (von Frey test) compared with Suture-only repairs (Figure 9).
These functional improvements are consistent with Remplir’s ability to support high quality nerve regeneration (superior central axonal alignment and improved distal axon myelination) and more favourable macrophage-mediated repair kinetics, which together promote more effective reinnervation.
Figure 9: Over the 24-week period, Remplir-assisted repairs consistently show comparatively greater motor recovery (Extensory Postural Thrust Force) and mechanosensory recovery (von Frey test) relative to Suture-only repairs, aligning with structural evidence of enhanced axonal regeneration and reinnervation.
Conclusion:
Across structural, morphometric, and immunological assessments, Remplir demonstrated a comparatively more favourable regenerative profile than both Suture-only and Comparator-assisted repairs. The use of Remplir supports high quality nerve regeneration with improved axonal organization distal nerve maturation (axon remyelination), a more timely transition from pro-inflammatory to pro-regenerative macrophage states, and earlier recovery of motor and sensory function. Together, Remplir provides a more supportive immune and regenerative microenvironment that delivers superior conditions and guidance for consistent nerve regeneration and clinical outcomes.
All animal procedures were performed in compliance with the Australian Code for the Care and Use of Animals for Scientific Purposes 8th Edition (2013), NSW Animal Research Act 1985 No 123, NSW Animal Research Regulation 2021, to the principles of Good Laboratory Practice for Nonclinical Laboratory Studies (FDA, OECD), and approved by the University of New South Wales (UNSW) Animal Care and Ethics Committee (ACEC Approval #22/127A).
References1. Leis A, Smetana BS, Strohl AB, Styron JF. Comparative Effectiveness Systematic Review and Meta-analysis of Peripheral Nerve Repair Using Direct Repair and Connector-assisted Repair. Plast Reconstr Surg Glob Open. 2024;12(7):e5927 2. Badylak SF, Valentin JE, et al. Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng Part A. 2008;14(11):1835-1842
White Paper
Interim results: Post-Market Clinical Follow-up Study to Evaluate the Safety and Performance of RemplirTM Collagen Membrane in Peripheral Nerve Surgery
1 Background
This document summarises the interim results from an Australian post-market clinical follow-up study, designed to collect data on the real-world safety and performance of Remplir when used in a range of different peripheral nerve surgical procedures. The study was prospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN12624001213538).
2 Methods
2.1 Study design
This is a multi-centre, prospective and retrospective observational study. The patient cohort includes those who receive Remplir as a part of normal clinical practice in the post-approval phase, as well as those who received a peripheral nerve procedure with Remplir prior to regulatory approval via the TGA’s special access scheme (excluding patients from the Remplir pre-market clinical trial). The period of follow-up for each participant is according to standard clinical practice at the site for the type of procedure, or for up to 24 months after receiving Remplir.
2.2 Eligibility criteria
This is a multi-centre, prospective and retrospective observational study. The patient cohort includes those who receive Remplir as a part of normal clinical practice in the post-approval phase, as well as those who received a peripheral nerve procedure with Remplir prior to regulatory approval via the TGA’s special access scheme (excluding patients from the Remplir pre-market clinical trial). The period of follow-up for each participant is according to standard clinical practice at the site for the type of procedure, or for up to 24 months after receiving Remplir.
Inclusion Criteria:
- Underwent a peripheral nerve procedure using Remplir
- If still in clinical follow-up, able to sign informed consent in accordance with ICH-GCP
Exclusion Criteria:
- Participated in the pre-market clinical study of Remplir
2.3 Outcome measures
The primary safety outcome is post-treatment complications related to Remplir. The primary performance outcome is treatment success according to the type and intent of the nerve procedure:
- For reconstruction of motor nerves, treatment success is defined (per muscle target) as functional motor recovery according to the British MRC scale (MRC ≥ 3).
- Procedures involving reconstruction of sensory nerves are assessed (per sensory region) by Semmes-Weinstein monofilament testing (SWMT) or Static two-point discrimination (S2PD), with functional sensory recovery defined as SWMT filament ≤ 3.61 or S2PD ≤ 15 mm.
- In procedures without nerve transection and reconstruction (e.g. nerve decompression procedures for carpal/cubital tunnel syndromes), treatment success is defined as improvement or complete relief of pre-operative symptoms according to a published grading scale.1
3 Results
3.1 Participant demographics and baseline characteristics
49 participants were included in the interim analysis, with a mean age of 46.8 years (range 14 to 82). These participants underwent a total of 67 peripheral nerve procedures, most commonly in the upper limb (82%). The majority (61.2%) were nerve reconstruction procedures (including nerve transfer and nerve graft ing) for acute injury, and 38.8% were nerve decompression procedures using Remplir as a protective wrap in participants with chronic nerve injuries such as carpal and cubital tunnel syndromes. In the participants with acute injury, 44% had an injury at the peripheral nerve level, 28% had a brachial plexus injury, and 28% had a cervical spinal cord injury.
3.2 Safety
The safety dataset includes all 49 participants (67 procedures). No post-treatment complications or adverse reactions to Remplir were reported for any of the participants.
3.3 Performance (treatment success)
33 participants (43 procedures) had sufficient follow-up data for inclusion in the performance dataset. Performance data is analysed according to therapeutic target. The number of therapeutic targets varies per procedure. In motor nerve reconstruction, a single procedure may result in restoration of function in multiple muscles, each of which is a therapeutic target. The target for nerve decompression procedures is relief of symptoms, therefore each decompression procedure only has one therapeutic target.
Across all procedure types there were 53 therapeutic targets included in the performance analysis. The overall treatment success rate according to pre-specified protocol criteria was 81.1% (43 of 53 therapeutic targets). Results are summarised by the main procedure types below.
Motor nerve reconstruction
A total of 12 participants underwent procedures to restore motor function in 22 nerves. Motor recovery was assessed by grading the strength of target muscles controlled by the repaired nerve in accordance with the British Medical Research Council grading system (MRC score). Results showed that 81.2% (26/32 target muscles) reached functional recovery (MRC 3 or 4) at an average of 8.3 months after surgical treatment with Remplir.
Figure 1 summarises the full dataset2 by percentage of target muscles in each MRC grade at each time point.
Figure 1 – Recovery of Muscle Power in Participants undergoing motor nerve reconstruction
Grade M3 and M4 – voluntary movement with improved strength and range of motion. Maximum level of recovery expected.
Grade M2 – voluntary movement restored, limited strength and range of movement.
Grade M0 or M1 – no voluntary movement.
Nerve decompression
19 participants provided performance data on nerve decompression procedures using Remplir. This included 8 carpal tunnel revision procedures, and 7 cubital tunnel procedures (5 primary, 2 revision). Results showed that 89.5% (17/19) of nerve decompression procedures resulted in significant improvement (most symptoms resolved) or complete relief of symptoms after treatment. No patients who received nerve decompression with Remplir required additional revision surgery during the follow up period.
Sensory nerve reconstruction
Only 2 sensory nerve reconstruction procedures were analysed. Although neither of the procedures met the protocol criteria for treatment success, both participants had improved sensory outcomes after surgery. One participant underwent a medial plantar nerve graft with Remplir and improved from having no sensation in their big toe and foot, to an SWMT filament result of 6.65. The other participant underwent a sensory nerve transfer (superficial radial nerve to median nerve) with Remplir for finger and thumb sensation, and improved from a SWMT result of 4.56 pre-surgery, to 4.31 post-treatment.
4 Summary
This interim analysis demonstrates the utility of Remplir in peripheral nerve surgical procedures ranging from nerve transfer for restoration of upper limb function after cervical spinal cord or brachial plexus injury, to decompression procedures in carpal and cubital tunnel syndromes. The safety and performance results are consistent with the clinical trial of Remplir published in the Journal of Reconstructive Microsurgery Open.3
This study continues in the recruitment phase, and ongoing data collection will facilitate analysis with a larger sample size and longer follow-up.
1 Jariwala A et al (2015). Outcome analysis of cubital tunnel decompression. Scott Med J. 2015;60(3):136-40. https://doi.org/10.1177/0036933015589487
2 Includes all data available at each time point. N=51 at baseline, N=41 at month 6, N=41 at month 12, N=22 at month 24/early discontinuation
3 O’Beirne, A et al (2024). Reconstruction of upper-extremity peripheral nerve injuries using an epineurial-like collagen device: A prospective clinical study. Journal of Reconstructive Microsurgery Open, 9(1). https://doi.org/10.1055/s-0044-1785213
White Paper
Biomechanical Comparison of Nerve Wrap Elasticity: RemplirTM vs Porcine Small Intestine Submucosa (SIS)
Introduction:
Elasticity is an essential property of nerve tissue. During everyday limb movements, peripheral nerves experience mechanical stresses such as strain and stretch, which they accommodate through their natural ability to glide and elongate.1
When a nerve is repaired with a nerve wrap product, it is beneficial for the wrap material to have have similar elasticity to the nerve tissue to avoid creating a mechanical mismatch that restricts nerve swelling and glide. Wraps that are too stiff can compress the healing nerve, reducing blood perfusion2 that can impair regeneration3 and function.4
Moreover, elasticity of nerve wraps can influence the rate of axonal regeneration and myelination after surgical repair of transected nerves.5
These findings suggest that nerve wraps with similar elasticity to nerve support natural nerve mechanics and optimize recovery.
Methods:
Percent elongation and Young’s modulus are two variables that describe how elastic a material is. Percent elongation reveals how much a material can stretch before it breaks; more stretch means the material is more flexible. Young’s modulus measures how hard it is to stretch the material; a higher value means it is stiffer.
An independent laboratory performed elasticity testing on samples of Remplir (n=67) and Axoguard Nerve Protector® (porcine SIS), Axogen® Corporation (n=11). The nerve wraps were trimmed to the same size (30x10mm) and hydrated before testing to mimic in vivo conditions. Each wrap was then loaded onto a tensile testing device that stretched the wrap at a rate of 25mm per minute. Data recorded from the tensile testing were used to calculate percent elongation and Young’s modulus.
Young’s modulus values for native nerve tissue were obtained from a published study.6 Median nerve specimens from nine cadavers were stored at −20°C and later tested at room temperature using a tensile testing device similar to that employed for the nerve wraps.
Results:
The average percent elongation of Remplir is over two times that of porcine SIS (Figure 1), a statistically significant difference (p<0.0001). Test results also show that Remplir can stretch by over 200%, which will accommodate nerve swelling after nerve repair.
Figure 1: Tensile testing shows Remplir can elongate significantly more than porcine SIS before failure. Data are mean ± SEM.
Test results also show that the porcine SIS nerve wrap is significantly stiffer than Remplir (p<0.0001). The average Young's modulus values were 17.9 for Remplir, 14.6 for human nerve, and 92.7 for porcine SIS (Figure 2). When the Young's modulus results are compared to human nerve,6 Remplir closely resembles human nerve (no significant difference) whereas porcine SIS does not.
Figure 2: Tensile testing shows the Young’s modulus value for Remplir is similar to human nerve6 and significantly lower than porcine SIS. Data are mean ± SEM unless otherwise stated.
Conclusion:
Elasticity of a material can be studied by measuring elongation and stiffness. These bench top data, produced by an independent laboratory, show that the elasticity of Remplir is comparable to human nerve and that Remplir can stretch to over 200% to accommodate nerve swelling after surgical repair. On both measures of elasticity, elongation and stiffness, results from Remplir were more physiologically relevant than the porcine SIS nerve wrap.
References: 1. Topp KS, Boyd BS. Structure and biomechanics of peripheral nerves: nerve responses to physical stresses and implications for physical therapist practice. Phys Ther. 2006;86(1):92-109. doi:10.1093/ptj/86.1.92 2. Ju MS, Lin CC, Fan JL, Chen RJ. Transverse elasticity and blood perfusion of sciatic nerves under in situ circular compression. J Biomech. 2006;39(1):97-102. doi:10.1016/j.jbiomech.2004.10.026 3. Malekzadeh H, Otto-Moudry R, Moore AM. The role of vascularization in nerve regeneration: mechanistic and therapeutic perspectives. Int J Mol Sci. 2025;26(17):8395. doi:10.3390/ijms26178395 4. Wall EJ, Massie JB, Kwan MK, Rydevik BL, Myers RR, Garfin SR. Experimental stretch neuropathy. Changes in nerve conduction under tension. J Bone Joint Surg Br. 1992;74(1):126-129. doi:10.1302/0301-620X.74B1.1732240 5. Liu F, Xu J, Liu A, et al. Development of a polyacrylamide/chitosan composite hydrogel conduit containing synergistic cues of elasticity and topographies for promoting peripheral nerve regeneration. Biomater Sci. 2022;10(17):4915-4932. Published 2022 Aug 24. doi:10.1039/d2bm00327a 6. Stouthandel MEJ, Vanhove C, Devriendt W, et al. Biomechanical comparison of Thiel embalmed and fresh frozen nerve tissue. Anat Sci Int. 2020;95(3):399-407. doi:10.1007/s12565-020-00535-1
White Paper
Safety Data Summary: RemplirTM
1. Introduction & Product Overview
This document summarises the safety profile of Remplir, with supporting evidence from Orthocell’s collagen medical device family.
Orthocell’s collagen medical device family consists of implantable collagen membranes of various thicknesses and sizes, designed for different clinical indications (nerve, bone, tendon and cartilage). The collagen membranes have been approved by global regulatory authorities (for use in both peripheral nerve repair and dental guided bone and tissue regeneration) and have been marketed/used in patients since 2017.
Remplir (peripheral nerve repair) is currently approved/cleared for use in Australia, New Zealand, Canada, United States, Singapore, Thailand and Hong Kong, and Striate+TM (guided bone and tissue regeneration) is currently approved/cleared in Australia, New Zealand, Europe, United Kingdom, United States, Switzerland, Singapore and Albania.
This white paper details the safety data summary of approved devices Remplir and Striate+, by reviewing data from inputs such as complaints, regulatory databases, literature, clinical data (inclusive of post-market clinical follow up studies), manufacturing data, scientific literature and market and customer feedback up until July 2025.
2. Safety Data Sources
Pre-clinical Testing:
- ISO 10993 biocompatibility series (cytotoxicity, sensitisation, irritation and sensitisation, local and systemic toxicity, pyrogenicity, genotoxicity).
- Animal testing (rat sciatic nerve and canine dental guided bone regeneration (GBR).
Clinical Data:
- Published clinical studies.
- Manufacturer-sponsored post-market clinical follow up studies.
Post-market Surveillance:
- Over 70,000 units sold globally.
- Vigilance reports, customer feedback, and regulatory databases.
Scientific Literature:
- Published studies on implantable collagen medical devices in the relevant therapeutic area.
3. Safety Data Summary
Pre-clinical:
- No evidence of inflammation or foreign body reactions were observed in animal testing.
- All ISO 10993 endpoints passed; no cytotoxicity, sensitisation, or irritation observed.
Clinical:
- No device related adverse events.
Post-market:
- No reportable adverse events of units sold worldwide.
Scientific Literature:
- Literature is consistent with established safety profile of collagen medical devices.
4. Conclusion
The data gathered from safety data continues to support the following conclusions:
- Orthocell’s collagen medical devices (Remplir & Striate+) are safe, and no new safety signals have been detected from post-market experience of over 70,000 device sales.
- The benefits of the use of the collagen medical device in its approved clinical indication (peripheral nerve repair or dental guided bone and tissue regeneration), outweigh any risks.
- The benefit-risk profile of the collagen medical device is favourable.
References :1. Regulatory Databases: Manufacturer and User Facility Device Experience (MAUDE); Recalls and Safety Alerts for Health Products (Canada); Medicines and Healthcare products Regulatory Agency (MHRA); Swissmedic (Switzerland); Device Adverse Event Notifications (DAEN) (Australia); Database of Recalls, Product Alerts and Product Corrections (DRAC) (Australia). 2. O’Beirne, A., Cullen, J., Landao-Bassonga, E., Zheng, M., Lee, C., Kaluskar, P., Tai, A., & Zheng, M. (2024). Reconstruction of upper-extremity peripheral nerve injuries using an epineurial-like collagen device: A prospective clinical study. Journal of Reconstructive Microsurgery Open, 9(1). https://doi.org/10.1055/s-0044-1785213. 3. Allan, B., Ruan, R., Landao-Bassonga, E., Gillman, N., Wang, T., Gao, J., Ruan, Y., Xu, Y., Lee, C., Goonewardene, M., & Zheng, M.-H. (2021). Collagen membrane for guided bone regeneration in dental and orthopedic applications. Tissue Engineering Part A, 27(5–6), 372–381. https://doi.org/10.1089/ten.tea.2020.0140
Case Study
CONNECT with RemplirTM
Trauma:
Motor vehicle, power tool, surgical injuries, sports and military related accidents
Male patient (21 years of age) with axillary nerve injury caused by GHJ dislocation four months prior to treatment. Patient presented with a dense axillary nerve palsy with avulsion just distal to the circumflex branch of the axillary artery with scarring +++ and 2cm adhesions on either side. Nerve transfer performed using radial nerve to medial head of triceps as donor. Remplir used to assist coaptation with significant size mismatch.
Case Courtesy of Dr Alex O’Beirne
Case Study
PROTECT with RemplirTM
Compression:
Blunt trauma, compression neuropathy (e.g. carpal/cubital tunnel)
Nerve wrapping with Remplir after surgical treatment for compression neuropathy can potentially improve patient outcomes. The smooth outer surface of Remplir consists of collagen bundles that are tightly packed, acting as a barrier between the epineurium and surrounding soft tissue. This feature of Remplir promotes nerve gliding and reduces the risk of adhesion formation after primary or revision surgery for compression neuropathy. As Remplir consists of collagen fibres that are similar in size and arrangement to normal human epineurium, it is an ideal scaffold for regeneration of healthy nerve tissue. Images below are of Remplir being used as a wrap in conjunction with carpal tunnel revision surgery.
Case Courtesy of Dr Alex O’Beirne
Case Study
CAP with RemplirTM
Iatrogenic:
Amputation, stump neuroma, mastectomy, schwannoma
Outcomes from three cases of peripheral nerve capping with reinnervation into adipose tissue for prophylaxis and management of neuroma were presented at the 2024 Combined Meeting of the American Society for Surgery of the Hand and the Australian Hand Surgery Society. After neurolysis and mobilization of the transected nerve, subcutaneous adipose tissue was harvested and placed around the nerve stump. Remplir was wrapped around the encased nerve end and sutured into a cap. The construct was then secured without tension in an adipose tissue pocket.
Cases courtesy of Dr David Gamble and Prof Richard Carey Smith
About us
Orthocell Ltd, headquartered in Perth, Australia, is the home of Remplir
Since 2010, we’ve been developing and exporting innovative regenerative medicine products worldwide. As of February 2026, more than 75,000 patients have benefited from an Orthocell collagen medical device, with no reportable adverse events. Every product reflects our mission: improving mobility, function, and quality of life. We collaborate with leading surgeons and centers of excellence to translate research into practical solutions that raise the standard of care. Our deep understanding of tissue engineering, particularly the interaction between cells and scaffolds, allows us to enhance the body’s natural healing and regeneration processes. Orthocell products are designed to simplify procedures, save operative time, and deliver consistent, predictable outcomes, supporting surgeons in providing the best care for their patients.
© 2026 Orthocell Ltd. All rights reserved. MK–0002025 v2.0