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.

Computer-simulated TOUCH prosthesis cup malposition and solutions.

INTRODUCTION: Total joint replacement has become significantly more common as a treatment for advanced trapeziometacarpal joint osteoarthritis in recent years. The latest generation of prostheses with dual-mobility designs leads to very good functional results and low rates of loosening and dislocation in the short and medium term. Biomechanical studies showed that central placement and parallel alignment of the cup with respect to the proximal articular surface of the trapezium are crucial for both cup stability and prevention of dislocation. Despite correct positioning of the guidewire, incorrect placement or tilting of the inserted cup may occur, requiring immediate intraoperative revision. METHODS: The existing spherical and conical cup models in sizes 9 mm and 10 mm were transferred to a computer-aided design dataset. Depending on the intraoperative complication (tilting or incorrect placement), the revision options resulting from the various combinations of cup type and size were simulated and analyzed according to the resulting defect area and bony contact area. RESULTS: In well centered cups, a size 9 conical cup could be replaced by a size 9 spherical cup and still be fixed by press-fit. Conversely, a size 9 spherical cup could not be replaced by a size 9 conical cup, but only by a size 10 cup, of whatever shape. When a size 9 conical cup was tilted up to 20°, the best revision option was to resect the sclerotic margin and insert a size 10 conical cup deeper into the cancellous bone, to achieve the largest contact area with the surrounding bone. When a size 9 cup of whatever shape was poorly centered (misplaced with respect to the dorsopalmar or radioulnar line of the trapezium), placement should be corrected using a size 10 cup, combined with autologous bone grafting of the defect. Again, the size 10 conical cup showed the largest bony contact area. CONCLUSION: Our computer-based measurements suggested options for intraoperative cup revision depending on cup shape and size and on type of misalignment with resulting bone defects. These suggestions, however, need to be confirmed in anatomic specimens before introducing them into clinical practice.

Hypoxia as a stimulus for tissue formation: The concept of organogenesis in microsurgically vascularized tissue engineering constructs.

Axial vascularization of tissue constructs is essential to maintain an adequate blood supply for a stable regeneration of a clinically relevant tissue size. The versatility of the arterio-venous loop (AVL) has been previously shown in various small and large animal models as well as in clinical reports for bone regeneration. We have previously demonstrated the capability of the AVL to induce axial vascularization and to support the nourishment of tissue constructs in small animal models after applying high doses of ionizing radiation comparable to those applied for adjuvant radiotherapy after head and neck cancer. We hypothesize that this robust ability to induce regeneration after irradiation could be related to a state of hypoxia inside the constructs that triggers the HIF1 (hypoxia induced factor 1) - SDF1 (stromal derived factor 1) axis leading to chemotaxis of progenitor cells and induction of tissue regeneration and vascularization. We analyzed the expression of HIF1 and SDF1 via immunofluorescence in axially vascularized bone tissue engineering constructs in Lewis rats 2 and 5 weeks after local irradiation with 9Gy or 15Gy. We also analyzed the expression of various genes for osteogenic differentiation (collagen 1, RUNX, alkaline phosphatase and osteonectin) via real time PCR analysis. The expression of HIF1 and SDF1 was enhanced two weeks after irradiation with 15Gy in comparison to non-irradiated constructs. The expression of osteogenic markers was enhanced at the 5-weeks time point with significant results regarding collagen, alkaline phosphatase and osteonectin. These results indicate that the hypoxia within the AVL constructs together with an enhanced SDF1 expression probably play a role in promoting tissue differentiation. The process of tissue generation triggered by hypoxia in the vicinity of a definite vascular axis with enhanced tissue differentiation over time resembles hereby the well-known concept of organogenesis in fetal life.

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.

Mid- and long-term clinical results of the Elektra and Moovis prosthesis for trapeziometacarpal joint replacement.

BACKGROUND: Total joint arthroplasty as a surgical treatment option for trapeziometacarpal joint arthritis is recently revived. The aim of this study is to report on mid- and long-term results of the Elektra (single-mobility) and Moovis (dual-mobility) prosthesis for treatment of primary thumb carpometacarpal joint arthritis. METHODS: In this retrospective, monocentric, descriptive cohort study, 31 prostheses were evaluated that were implanted by a single surgeon in 26 patients between 2009 and 2019. Indication for surgery was trapeziometacarpal joint osteoarthritis (Eaton/Littler Stage II and III). Clinical and radiological follow-up was performed at a minimum of 24 months. The postoperative assessment included range of motion, pain, strength as well as functional scores (DASH, MHQ). Implant survival and complications were the primary endpoints. RESULTS: 10 Elektra and 21 Moovis prostheses were implanted between 2009 and 2019 with a mean follow-up of 74.2 months in the Elektra and 41.4 months in the Moovis group. The average patients' age at surgery was 64 years. Postoperative pain levels (VAS 0-10) were below 2 at rest and under stress in both groups. Grip/pinch strength and range of motion showed results comparable to the contralateral hand. Opposition was excellent with an average Kapandji index of 9.6 in both groups. Elektra achieved slightly better functional scores in the DASH and MHQ score. Satisfaction was high in both groups, and 96% of the patients would recommend the procedure. Metacarpophalangeal hyperextension > 15° was seen in 3 patients per group preoperatively and was corrected to < 5° post-surgery. 3 Elektra prostheses were revised due to cup loosening and dislocation for cup and/or neck replacement or secondary trapeziectomy. 1 Moovis prosthesis was revised with an exchange of the neck to a larger size due to restricted movement. After the mean follow-up of 7.9 years in Elektra and 3.5 years in MOOVIS, cumulative survival was 68.6% vs. 95.2%, respectively. CONCLUSIONS: In this mid- to long-term retrospective analysis, total joint arthroplasty in primary trapeziometacarpal joint arthritis results in low pain levels, excellent mobility and clinical function. Patient satisfaction is overall high. While revision due to cup loosening occurred more often in patients with single-mobility implants, no cases of dislocation or loosening of components were observed in the dual-mobility group. TRIAL REGISTRATION: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of the Medical Faculty of Heidelberg University, reference number S-150/2020.

Comparative analysis of surgical treatment modalities for a popliteal pterygium: a meta-analysis.

INTRODUCTION: Popliteal pterygium syndrome is a rare congenital disorder characterized by orofacial, cutaneous, musculoskeletal, and genital anomalies. The popliteal pterygium (PP) affects ambulation due to severe knee flexion contracture and equinovarus deformities. Surgical treatment aims to correct these deformities while preserving limb sensibility. However, due to its rarity, surgical guidelines are lacking. MATERIALS AND METHODS: A meta-analysis according to PRISMA guidelines was conducted to summarize and compare surgical methods for PP. 183 paper were identified in PubMed and data from 32 articles were analyzed, including patient demographics, treatment modalities (Ilizarov fixator, femoral osteotomy, skin/soft tissue procedures, hamstring release, nerve surgery, and amputation), pre- and post-operative abilities to walk, knee joint parameters, complications, and recurrent contractions. RESULTS: Among 58 patients (87 limbs), Ilizarov fixator demonstrated improved knee and ankle mobility postoperatively, but showed a relatively high surgical session count and complication rates. Femoral osteotomy achieved successful knee posture correction with fewer sessions and no complications. Isolated skin/soft tissue procedures improved flexion contracture and mobility, though they required several procedures. Hamstring release achieved notable contracture reduction but also necessitated multiple interventions. Nerve surgery and amputation had limited data, warranting further investigation. CONCLUSION: The management of PP demands a comprehensive approach, considering individual patient characteristics and treatment outcomes. While different surgical modalities offer distinct benefits, a classification or guideline to treat this deformity is still lacking. Further research is essential to validate findings, refine treatment approaches, and enhance the quality of life for individuals with PP.

The research question: the What, Why and How in hand surgery.

Identifying a good research question is one of the most important steps when laying the foundation of a research project. A good research question can aim to answer a hotly debated clinical issue, challenge a pre-existing dogma or make a contribution to specific aspects of a broader field of study. The difficulty in defining the question lies with pinpointing an important research topic or an area that is characterized by a lack of knowledge (the What), grasping the significance of how a precisely defined study can potentially impact on clinical practices (the Why) and determining the optimal study design tailored to answer the specific question (the How). These three domains constitute pivotal concepts in the process of shaping the research question.

[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.

The long-term intercorrelation between post-burn pain, anxiety, and depression: a post hoc analysis of the "RE-ENERGIZE" double-blind, randomized, multicenter placebo-controlled trial.

BACKGROUND: Despite the growing prevalence of burn survivors, a gap persists in our understanding of the correlation between acute burn trauma and the long-term impact on psychosocial health. This study set out to investigate the prevalence of long-term pain and symptoms of anxiety and depression in survivors of extensive burns, comparing this to the general population, and identify injury and demographic-related factors predisposing individuals to psychosocial compromise. METHODS: RE-ENERGIZE was an international, double-blinded, randomized-controlled trial that enrolled 1200 patients with partial- or full-thickness burns that required surgical treatment. For the post hoc analysis, we excluded participants who did not complete the Short Form Health Survey (SF-36) questionnaire. Normative data were taken from the 2021 National Health Interview Survey dataset. Propensity score matching was performed using the nearest-neighbor 1-to-1 method, and the two cohorts were compared in terms of chronic pain, and symptoms of anxiety and depression. A multivariable analysis was performed on the burns cohort to identify factors predicting post-discharge pain and symptoms of anxiety and depression. RESULTS: A total of 600 burn patients and 26,666 general population adults were included in this study. Following propensity score matching, both groups comprised 478 participants each, who were predominately male, white, overweight and between 20 and 60 years old. Compared to the general population, burn patients were significantly more likely to report the presence of moderate and a lot of pain (p = 0.002). Symptoms of anxiety were significantly higher in the burn population in two of four levels (most of the time; some of the time; p < 0.0001 for both). Responders in the burn population were significantly less likely to report the absence of depressive symptoms (p < 0.0001). Burn patients were also significantly more likely to report that their mental health affects their social life. TBSA, history of depression, and female sex were identified as independently associated factors for pain, anxiety, and depressive symptoms. The presence of chronic pain and anxiety symptoms independently predicted for symptoms of depression. CONCLUSIONS: Analyzing the largest multicenter cohort of patients with extensive burns, we find that burn injury is associated with chronic pain, and symptoms of anxiety and depression. In addition, TBSA-burned and history of depression directly correlate with the prevalence of chronic pain, and symptoms of anxiety and depression. Finally, pain, and symptoms of anxiety and depression are interrelated and may have interactive effects on the process of recovery following burn injury. Burn patients would, therefore, benefit from a multidisciplinary team approach with early mobilization of pain and mental health experts, in order to promptly prevent the development of psychosocial challenges and their consequences.

Revealing digital nerve lesions-A comprehensive analysis of 2084 cases of a specialized center.

BACKGROUND: Finger nerve injuries have a significant impact on hand function and can result in reduced sensation, pain and impaired coordination. The socioeconomic implications of these injuries include decreased workplace productivity, reduced earning potential, and financial burdens associated with long-term medical treatment and rehabilitation. However, there is a lack of comprehensive literature regarding the incidence, mechanisms, and associated injuries of finger nerve lesions. METHODS: A retrospective analysis was conducted on patients treated at our institution from January 2012 to July 2020. Cases of peripheral finger nerve lesions were identified using the digital hospital information system and ICD-10 Classification. Exclusion criteria included injuries to the median nerve at the carpal tunnel level or superficial branch of the radial nerve. Data were collected using a pseudonymized approach, and statistical analyses were performed using SPSS Statistics (Version 27). RESULTS: A total of 2089 finger nerve lesions were analyzed, with a majority of cases occurring in men. Most injuries97.4 % were caused by trauma, predominantly cut/tear injuries. Isolated finger nerve injuries were more common than multiple nerve injuries, with the index finger being the most frequently affected. Concomitant tendon and vascular injuries were observed in a significant proportion51.7 % of cases. Surgical management included direct nerve coaptation, interposition grafting and neurolysis. DISCUSSION: Finger nerve injuries are the most prevalent type of nerve injury, often resulting from small lacerations. These injuries have substantial societal costs and can lead to prolonged sick leave. Understanding the epidemiology and etiology of finger nerve injuries is crucial for implementing effective preventive measures. Accompanying tendon injuries and the anatomical location of the nerve lesions can impact sensory recovery and treatment outcomes. Proper management of peripheral finger nerve lesions is essential for optimizing functional outcomes and minimizing the impact on daily activities. Treatment options should be tailored to the severity and underlying cause of the nerve injury.

[Nerve Transfers in Peripheral Nerve Lesions]. / Nerventransfers bei peripheren Nervenläsionen.

BACKGROUND: Lesions of peripheral nerves of the upper extremities often lead to persistent, serious limitations in motor function and sensory perception. Affected patients suffer from both private and professional restrictions associated with long-term physical, psychological and socioeconomic consequences. INDICATION: An early indication for a nerve transfer shortens the reinnervation distance and improves the growing of motor and sensory axons into the target organ to facilitate early mobility and sensitivity. When planning the timepoint of the surgical procedure, the distance to be covered by reinnervation as well as the morbidities of donor nerves must be considered individually. RESULTS: Nerve transfers can achieve earlier and safer reinnervation to improve motor and sensory functions after nerve injuries in the upper extremity.

Indication-specific effect of a phytotherapeutic remedy on human fetal osteoblastic cells: An in-vitro analysis.

Background Impaired fracture healing is a recurring interdisciplinary medical challenge. Alternative treatment concepts, apart from conventional medicine are popular, but scientific evidence on their effects is still lacking. Plant-derived substances are widely assumed to support bone homeostasis. To clarify the effects on bone healing mechanisms, a commercially available, homeopathic-spagyric remedy, containing inter alia two herbal substances with assumed osteogenic potential, equisetum arvense and bellis perennis, was analyzed. Methods Human fetal osteoblastic cells (hFOB1.19) were incubated with the test substance, in serial dilutions from 10 to 0,00001 %. Cell viability has been evaluated through ATP level (CTG assay) and MTT tetrazolium reduction. Cell proliferation was analyzed by BrdU incorporation and cell migration by wound healing assay (WHA) via image analysis. Additionally, determination of the expression of key genes via real-time PCR and proteins via Proteome Array for inflammation, cell proliferation and angiogenesis were performed. Results An incubation of hFOB 1.19 with the test substance for 24/72 hours showed no reduction in cell number, viability or proliferation. Cell migration was unimpaired. The test substance induced inflammatory genes and growth factors along with genes of osseous regeneration. (ALP, Col1, IL-1α, IL-6, IL-8, IL-10, Osteocalcin, Osteonectin, RUMX2, TGF, VEGFA). Increased protein expression was found in multiple cytokines, chemokines and acute phase proteins. Conclusion The test substance did not impair cell vitality parameters (MTT, CTG, BrdU and WHA). A tendency to activate growth factors, bone regeneration genes and proteins was shown for osteoblasts, indicating a possible positive effect on osteogenic processes.

Ultrasound-An Easy Available and Useful Point-of-Care Adjunct for Clinical Decision-Making in Hand Infections: Review of the Literature and a Case Series.

ABSTRACT: Initial findings of hand infections warrant a thorough treatment strategy depending on the progress of the infection. The decision for surgical treatment can be unclear. Searching to improve the quality of diagnostics, we reviewed the literature regarding the use of point-of-care ultrasound (PCUS) in hand infections and analyzed patients undergoing decision-making with PCUS. We searched PubMed, Scopus, Cochrane Register, and Google Scholar for the use of PCUS in therapy planning in infections of the hand. In addition, we screened our patients from July 1, 2020, to November 30, 2020, to validate the potential benefit of ultrasound examination in suspected hand infections. We evaluated initial clinical examinations versus blinded sonographic assessments in the context of correct decision to proceed with surgery or conservative treatment. Two thousand forty-eight studies within the topic were identified, but only 9 studies were found eligible to be included with a total of 88 patients. The studies illustrate that ultrasound can be performed on all patients, including children and pregnant women, and can be performed in a timely manner. In our retrospective analysis of 20 patients with suspected hand infection, the clinical and ultrasound assessment led to surgery in 13 cases. Of those 13 patients, 7 revealed intraoperative pus. By retrospective assessment of solely the ultrasound images, surgery would have been indicated in 9 cases, including all 7 cases with intraoperative pus. Clinical examination and ultrasound can help in detecting infections of the hand. Ultrasound examination, however, seems to yield a lower false-positive rate than clinical examination. Ultrasound could be a valuable addition to clinical examination.

A Systematic Review and Illustrative Case Presentation of Low-Grade Myofibroblastic Sarcoma (LGMS) of the Extremities.

INTRODUCTION: Low-grade myofibroblastic sarcoma (LGMS) is a rare tumor entity which occurs in the subcutaneous and deep soft tissues; it is less common in the bone with a predilection for the extremities and the head and neck region. As confirming the diagnosis is difficult and treatment strategies are not standardized, we aimed to identify patient and tumor characteristics, and to summarize treatment strategies and their clinical outcomes to guide surgeons. METHODS: Included were full articles reporting patients with histology of LGMS in the extremities, excluding tumors of the trunk. All patients underwent surgery but with different extend, from marginal to wide resection. Included studies should inform about local recurrence, metastasis, or evidence of disease, depending on the surgical treatment. We conducted a structured search using MEDLINE (via PubMed), Web of Science, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) to identify studies on low-grade myofibroblastic sarcoma of the extremities. Study designs like randomized controlled trials, systematic reviews, prospective trials, retrospective studies, and case reports were included. Prospective studies and comparative studies were not available at all. Therefore, meta-analysis was not possible and statistical analysis was purely descriptive. RESULTS: Of the 789 studies identified from our initial search, 17 studies including 59 cases reported LGMS of the extremities with the surgical treatment and clinical outcome and were therefore analyzed. In addition, we present the rare case and surgical management of a 28-year-old male patient with residual LGMS of the thumb after an initial incomplete resection. The current literature suggests that a wide excision with R0 margins should be considered the standard treatment for LGMS. In cases where surgery leads to significant functional impairment, individual options like free tissue transfer from a donor site have to be considered. Therefore, we also present an illustrative case. For all selected case series and case reports, a high risk of confounding, selection bias, information bias, and reporting bias must be anticipated. Nevertheless, this systematic review provides a comprehensive overview on surgical treatment and clinical outcomes in LGMS surgery of the extremities.

Improving outcomes in traumatic peripheral nerve injuries to the upper extremity.

Peripheral nerve lesions of the upper extremity are common and are associated with devastating limitations for the patient. Rapid and accurate diagnosis of the lesion by electroneurography, neurosonography, or even MR neurography is important for treatment planning. There are different therapeutic approaches, which may show individual differences depending on the injured nerve. If a primary nerve repair is not possible, several strategies exist to bridge the gap. These may include autologous nerve grafts, bioartificial nerve conduits, or acellular nerve allografts. Tendon and nerve transfers are also of major importance in the treatment of nerve lesions in particular with long regeneration distances. As a secondary reconstruction, in addition to tendon transfers, there is also the option for free functional muscle transfer. In amputations, the prevention of neuroma is of great importance, for which different strategies exist, such as target muscle reinnervation, regenerative peripheral nerve interface, or neurotized flaps. In this article, we give an overview of the latest methods for the therapy of peripheral nerve lesions.

Regulatory T cells in skin regeneration and wound healing.

As the body's integumentary system, the skin is vulnerable to injuries. The subsequent wound healing processes aim to restore dermal and epidermal integrity and functionality. To this end, multiple tissue-resident cells and recruited immune cells cooperate to efficiently repair the injured tissue. Such temporally- and spatially-coordinated interplay necessitates tight regulation to prevent collateral damage such as overshooting immune responses and excessive inflammation. In this context, regulatory T cells (Tregs) hold a key role in balancing immune homeostasis and mediating cutaneous wound healing. A comprehensive understanding of Tregs' multifaceted field of activity may help decipher wound pathologies and, ultimately, establish new treatment modalities. Herein, we review the role of Tregs in orchestrating the regeneration of skin adnexa and catalyzing healthy wound repair. Further, we discuss how Tregs operate during fibrosis, keloidosis, and scarring.

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.

Advancing Nerve Regeneration: Translational Perspectives of Tacrolimus (FK506).

Peripheral nerve injuries have far-reaching implications for individuals and society, leading to functional impairments, prolonged rehabilitation, and substantial socioeconomic burdens. Tacrolimus, a potent immunosuppressive drug known for its neuroregenerative properties, has emerged in experimental studies as a promising candidate to accelerate nerve fiber regeneration. This review investigates the therapeutic potential of tacrolimus by exploring the postulated mechanisms of action in relation to biological barriers to nerve injury recovery. By mapping both the preclinical and clinical evidence, the benefits and drawbacks of systemic tacrolimus administration and novel delivery systems for localized tacrolimus delivery after nerve injury are elucidated. Through synthesizing the current evidence, identifying practical barriers for clinical translation, and discussing potential strategies to overcome the translational gap, this review provides insights into the translational perspectives of tacrolimus as an adjunct therapy for nerve regeneration.

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.

Mechanisms, interventions at risk and clinical presentation of iatrogenic nerve lesions in trauma patients.

BACKGROUND: Iatrogenic nerve lesions during surgical interventions are avoidable complications that may cause severe functional impairment. Hereby, awareness of physicians and knowledge of structures and interventions at risk is of utmost importance for prevention. As current literature is scarce, we evaluated all patients treated surgically due to peripheral nerve injuries in our specialized nerve center for the presence of iatrogenic nerve lesions. METHODS: We evaluated a total of 5026 patients with peripheral nerve injuries treated over a time period of 8 years in our facility for the prevalence of iatrogenic nerve injuries, their clinical presentations, time to treatment, mechanisms and intraoperative findings on nerve continuity. RESULTS: A total of 360 (6.1%) patients had an iatrogenic cause resulting in 380 injured nerves. 76.6% of these lesions affected the main branch of the injured nerve, which were mainly the radial (30.5%), peroneal (13.7%) and median nerve (10.3%). After a mean delay of 237 ± 344 days, patients presented 23.2% with a motor and 27.9% with a mixed sensory and motor deficit. 72.6% of lesions were in-continuity lesions. Main interventions at risk are displayed for every nerve, frequently concerning osteosyntheses but also patient positioning and anesthesiologic interventions. DISCUSSION: Awareness of major surgical complications such as iatrogenic nerve injuries is important for surgeons. An often-seen trivialization or "watch and wait" strategy results in a huge delay for starting an adequate therapy. The high number of in-continuity lesions mainly in close proximity to osteosyntheses makes diagnosis and treatment planning a delicate challenge, especially due to the varying clinical presentations we found. Diagnostics and therapy should therefore be performed as early as possible in specialized centers capable of performing nerve repair as well as salvage therapies.