Inferior long-term Results of a Prospective Randomized Controlled Trial initially demonstrating enhanced Sensory Nerve Recovery using a Chitosan Nerve Tube.

INTRODUCTION: Traumatic peripheral nerve injuries can result in significant functional impairments and long-term sequelae. This study evaluated the long-term outcomes of a chitosan tube implantation protecting the epineural coaptation after peripheral nerve injuries using two different tube versions (V 1.0 and V 2.0 with different wall thickness and resorption characteristics) compared to a control group. The study focused on pain levels, sensory function, and overall functional outcomes. METHODS: Patients who received tube implantation around direct coaptation sites of digital nerves were prospectively randomized and compared to control patients without additional tube protection. Pain levels, sensory function, grip force, and functional scores were assessed at different time points, ranging from three months to five years after the procedure. Furthermore, biodegradation of the tubes was measured via high-resolution MR-neurography (MRN) and categorized. RESULTS: Long-term evaluation revealed that patients with V 1.0 had higher pain levels compared to the control group after five years. They also reported more symptoms of numbness and hypersensitivity. V 2.0 patients exhibited higher pain levels at three months, which did not persist at six months. However, they showed compromised sensory function, with higher values of two-point discrimination compared to V 1.0 and the control group. No differences were found in grip force or functional scores between the groups. MRI displayed remnants of implants even in long-term follow-up. DISCUSSION: The findings suggest potential limitations due to pain increase and impaired sensory function associated with tube implantation in the long term. However, in the short term, the material seemed to have a protective effect (as published previously). The resorption process was not completed at the end of the observation period of five years. This might explain the prolonged scarring and inferior long-term results. Future research should focus on improving tube materials and design to minimize adverse effects and enhance functional outcomes in patients with peripheral nerve injuries.

Fibrin Glue Coating Limits Scar Tissue Formation around Peripheral Nerves.

Scar tissue formation presents a significant barrier to peripheral nerve recovery in clinical practice. While different experimental methods have been described, there is no clinically available gold standard for its prevention. This study aims to determine the potential of fibrin glue (FG) to limit scarring around peripheral nerves. Thirty rats were divided into three groups: glutaraldehyde-induced sciatic nerve injury treated with FG (GA + FG), sciatic nerve injury with no treatment (GA), and no sciatic nerve injury (Sham). Neural regeneration was assessed with weekly measurements of the visual static sciatic index as a parameter for sciatic nerve function across a 12-week period. After 12 weeks, qualitative and quantitative histological analysis of scar tissue formation was performed. Furthermore, histomorphometric analysis and wet muscle weight analysis were performed after the postoperative observation period. The GA + FG group showed a faster functional recovery (6 versus 9 weeks) compared to the GA group. The FG-treated group showed significantly lower perineural scar tissue formation and significantly higher fiber density, myelin thickness, axon thickness, and myelinated fiber thickness than the GA group. A significantly higher wet muscle weight ratio of the tibialis anterior muscle was found in the GA + FG group compared to the GA group. Our results suggest that applying FG to injured nerves is a promising scar tissue prevention strategy associated with improved regeneration both at the microscopic and at the functional level. Our results can serve as a platform for innovation in the field of perineural regeneration with immense clinical potential.

Neuroma Analysis in Humans: Standardizing Sample Collection and Documentation.

INTRODUCTION: The biology of symptomatic neuromas is poorly understood, particularly the factors causing pain in human neuromas. Pain presence varies among and within individuals, with some having painful and nonpainful neuromas. To bridge these knowledge gaps, our group developed a protocol for assessing neuroma pain and collecting tissue for molecular analysis. This manuscript outlines our workflow and challenges and aims to inspire other centers to share their experiences with these tissues. METHODS: For every included patient and collected nerve or bone tissue specimens, we perform a detailed chart review and a multifaceted analysis of pain and pain perception immediately before surgery. We collect patient-reported outcome measures (PROMs) on pain, function, and mental well-being outcomes at preoperative assessment and at the 6-month follow-up postoperatively. Before surgery, the patient is assessed once again to obtain an immediate preoperative pain status and identify potential differences in pain intensity of different neuromas. Intraoperatively, specimens are obtained and their gross anatomical features are recorded, after which they are stored in paraformaldehyde or frozen for later sample analyses. Postoperatively, patients are contacted to obtain additional postoperative PROMs. RESULTS: A total of 220 specimens of nerve tissue have been successfully obtained from 83 limbs, comprising 95 specimens of neuromas and 125 specimens of nerves located proximal to the neuromas or from controls. CONCLUSIONS: Our approach outlines the methods combining specimen collection and examination, including both macroscopic and molecular biological features, with PROMs, encompassing physical and psychological aspects, along with clinical metadata obtained through clinical teams and chart review.

[Bionic Surgery Meets Bionic Reconstruction - First In-human use of Robotic Microsurgery in Targeted Muscle Reinnervation]. / Bionische Chirurgie trifft Bionische Rekonstruktion ­ erstes in-human Projekt von robotischer Mikrochirurgie zur Targeted Muscle Reinnervation.

Robotic microsurgery is an emerging field in reconstructive surgery, which provides benefits such as improved precision, optimal ergonomics, and reduced tremors. However, only a few robotic platforms are available for performing microsurgical procedures, and successful nerve coaptation is still a challenge. Targeted muscle reinnervation (TMR) is an innovative reconstructive procedure that rewires multiple nerves to remnant stump muscles, thereby reducing neuroma and phantom limb pain and improving the control of bionic prostheses. The precision of surgical techniques is critical in reducing axonal sprouting around the coaptation site to minimise the potential for neuroma formation. This study reports the first use of a microsurgical robotic platform for multiple nerve transfers in a patient undergoing TMR for bionic extremity reconstruction. The Symani robotic platform, combined with external microscope magnification, was successfully used, and precise handling of nerve tissue and coaptation was easily feasible even in anatomically challenging environments. While the precision and stability offered by robotic assistance may be especially useful for nerve surgery, the high economic costs of robotic microsurgery remain a major challenge for current healthcare systems. In conclusion, this study demonstrated the feasibility of using a robotic microsurgical platform for nerve surgery and transfers, where precise handling of tissue is crucial and limited space is available. Future studies will explore the full potential of robotic microsurgery in the future.

Three Useful Tips and Tricks for Intraoperative Nerve Stimulation.

Disposable handheld nerve stimulators are widely used in peripheral nerve surgery. Such devices stimulate a motor nerve or the motor component of a mixed nerve by applying electrical current to the proximal region, targeting the main nerve trunk. This stimulation then travels along the motor nerve, reaching the distal end to control the corresponding muscle(s). In this study, the authors demonstrate three useful tips and tricks for handheld nerve stimulation during targeted muscle reinnervation and peripheral nerve surgery. The three tips are (1) identification of proximal muscle contraction by retrograde electrical stimulation of a distal sensory nerve; (2) graded stimulation for identifying motor nerves within fibrotic scarred tissue beds or parallel to the major motor/mixed nerve of interest; and (3) proximal stimulation for validation of adequate post-targeted muscle reinnervation coaptation(s).

Shielding the Nerve: A Systematic Review of Nerve Wrapping to Prevent Adhesions in the Rat Sciatic Nerve Model.

BACKGROUND: Peripheral nerve pathology is frequently encountered in clinical practice among peripheral nerve and extremity surgeons. One major factor limiting nerve regeneration and possibly leading to revision surgeries is the development of traumatic or postoperative adhesions and scarring around nerves. In experimental models, different materials have been studied to limit scar tissue formation when wrapped around nerves. METHODS: A systematic review of studies describing nerve-wrapping materials in a non-transectional rat sciatic nerve model was performed following the PRISMA guidelines. Literature describing nerve-wrapping methods for the prevention of peripheral nerve scarring in rat sciatic nerve models was identified using PubMed and Web of Science, scanned for relevance and analyzed. RESULTS: A total of 15 original articles describing 23 different materials or material combinations for nerve wrapping were included. The heterogeneity of the methods used did not allow a meta-analysis, thus, a systematic review was performed. Out of 28 intervention groups, 21 demonstrated a preventive effect on scar tissue formation in at least one qualitative or quantitative assessment method. CONCLUSIONS: The analyzed literature describes a variety of materials from different origins to limit peripheral nerve scarring and adhesions. Thus, a scar-preventive effect by wrapping peripheral nerves as adhesion prophylaxis seems likely. However, a quantitative comparison of the studies to identify the optimal material or technique is not possible with the diversity of used models and study designs. Therefore, further research needs to be performed to identify the optimal nerve wraps to be used routinely in clinical practice.

Avoiding scar tissue formation of peripheral nerves with the help of an acellular collagen matrix.

INTRODUCTION: Extensive scar tissue formation after peripheral nerve injury or surgery is a common problem. To avoid perineural scarring, implanting a mechanical barrier protecting the nerve from inflammation processes in the perineural environment has shown promising results for functional recovery. This study investigates the potential of an acellular collagen-elastin matrix wrapped around a peripheral nerve after induction of scar tissue formation. MATERIALS AND METHODS: In the present study, 30 Lewis rats were separated into three groups and sciatic nerve scarring was induced with 2.5% glutaraldehyde (GA-CM) or 2.5% glutaraldehyde with a supplemental FDA-approved acellular collagen-elastin matrix application (GA+CM). Additionally, a sham group was included for control. Nerve regeneration was assessed by functional analysis using the Visual Statisc Sciatic Index (SSI) and MR neurography during the 12-week regeneration period. Histological and histomorphometry analysis were performed to evaluate the degree of postoperative scar tissue formation. RESULTS: Histological analysis showed an extensive scar tissue formation for GA-CM. Connective tissue ratio was significantly (p < 0.009) reduced for GA+CM (1.347 ± 0.017) compared to GA-CM (1.518 ± 0.057). Similarly, compared to GA+CM, MR-Neurography revealed extensive scar tissue formation for GA-CM with a direct connection between nerve and paraneural environment. Distal to the injury site, quantitative analysis presented significantly higher axon density (p = 0.0145), thicker axon diameter (p = 0.0002) and thicker myelinated fiber thickness (p = 0.0008) for GA+CM compared to GA-CM. Evaluation of functional recovery revealed a significantly faster regeneration for GA+CM. CONCLUSION: The supplemental application of an acellular collagen-elastin matrix showed beneficial effects in histological, radiological, and functional analysis. Therefore, applying a collagen-elastin matrix around the nerve after peripheral nerve injury or surgery may have beneficial effects on preventing scar tissue formation in the long run. This represents a feasible approach to avoid scar tissue formation in peripheral nerve surgery.

Benefit of Adjuvant Mesenchymal Stem Cell Transplantation to Critical-Sized Peripheral Nerve Defect Repair: A Systematic Review and Meta-Analysis of Preclinical Studies.

Critically sized nerve defects cause devastating life-long disabilities and require interposition for reconstruction. Additional local application of mesenchymal stem cells (MSCs) is considered promising to enhance peripheral nerve regeneration. To better understand the role of MSCs in peripheral nerve reconstruction, we performed a systematic review and meta-analysis of the effects of MSCs on critically sized segment nerve defects in preclinical studies. 5146 articles were screened following PRISMA guidelines using PubMed and Web of Science. A total of 27 preclinical studies (n = 722 rats) were included in the meta-analysis. The mean difference or the standardized mean difference with 95% confidence intervals for motor function, conduction velocity, and histomorphological parameters of nerve regeneration, as well as the degree of muscle atrophy, was compared in rats with critically sized defects and autologous nerve reconstruction treated with or without MSCs. The co-transplantation of MSCs increased the sciatic functional index (3.93, 95% CI 2.62 to 5.24, p < 0.00001) and nerve conduction velocity recovery (1.49, 95% CI 1.13 to 1.84, p = 0.009), decreased the atrophy of targeted muscles (gastrocnemius: 0.63, 95% CI 0.29 to 0.97 p = 0.004; triceps surae: 0.08, 95% CI 0.06 to 0.10 p = 0.71), and promoted the regeneration of injured axons (axon number: 1.10, 95% CI 0.78 to 1.42, p < 0.00001; myelin sheath thickness: 0.15, 95% CI 0.12 to 0.17, p = 0.28). Reconstruction of critically sized peripheral nerve defects is often hindered by impaired postoperative regeneration, especially in defects that require an autologous nerve graft. This meta-analysis indicates that additional application of MSC can enhance postoperative peripheral nerve regeneration in rats. Based on the promising results in vivo experiments, further studies are needed to demonstrate potential clinical benefits.