Search Results (161)

Approximately 185,000 people in the United states experience limb loss each year. There is a need for an intuitive neural interface that can offer high-fidelity control signals to optimize the advanced functionality of prosthetic devices. Regenerative peripheral nerve interface (RPNI) is a pioneering advancement in neuroengineering that combines surgical techniques with biocompatible materials to create an interface for individuals with limb loss. RPNIs are surgically constructed from autologous muscle grafts that are neurotized by the residual peripheral nerves of an individual with limb loss. RPNIs amplify neural signals and demonstrate long term stability. In this narrative review, the terms “Regenerative Peripheral Nerve Interface (RPNI)” and “RPNI surgery” are used interchangeably to refer to the same surgical and biological construct. This narrative review specifically focuses on RPNIs as a targeted approach to enhance prosthetic control through surgically created nerve–muscle interfaces. This area of research offers a promising solution to overcome the limitations of existing prosthetic control systems and could help improve the quality of life for people suffering from limb loss. It allows for multi-channel control and bidirectional communication, while enhancing the functionality of prosthetics through improved sensory feedback. RPNI surgery holds significant promise for improving the quality of life for individuals with limb loss by providing a more intuitive and responsive prosthetic experience. Full article

Background: Peripheral nerve injuries, especially involving the facial nerve, present unique reconstructive challenges due to their complex functional demands and limited regenerative potential. While autografts remain the gold standard, their drawbacks—such as donor-site morbidity and limited availability—have driven interest in processed nerve allografts. Acellular grafts, in particular, offer promising off-the-shelf alternatives without the need for immunosuppression. Methods: We conducted a narrative review of the literature (1990–2023), identifying 55 peer-reviewed studies via PubMed, Embase, and Cochrane Library. The studies included clinical and preclinical work on motor nerve regeneration using processed nerve allografts, with particular attention to outcomes in facial nerve repair. Two independent reviewers conducted abstract screening, full-text review, and data extraction. Results: Processed nerve allografts show encouraging motor recovery in gaps under 50 mm, with recovery rates of up to 85% reported. Outcomes decrease significantly in longer gaps (>50–60 mm) and in complex cases, including facial nerve repairs, where evidence remains sparse and largely extrapolated from broader motor nerve data. Registry data (e.g., RANGER) support their use but are limited by heterogeneity and lack of randomization. Conclusions: Processed nerve allografts represent a viable alternative to autografts in selected cases—especially short to mid-length motor nerve defects. However, their role in facial nerve reconstruction remains insufficiently studied. Further trials are needed to address specific anatomical and functional challenges in this subgroup and to clarify long-gap efficacy. Full article

Background/Objectives: Nerve injuries cause functional loss and psychosocial issues due to prolonged rehabilitation. Recently, 3D-modeled nerve conduits have been used to aid in surgical planning. This study investigated the impact of 3D-bioprinted PLA, chitosan, alginate, and collagen conduits on nerve regeneration in a rat sciatic nerve crush injury model. Methods: This study, conducted at Kütahya University of Health Sciences, involves 50 rats were divided into four groups: (1) sham-operated controls, (2) sciatic nerve injury without treatment, (3) injury treated with a PLA conduit, and (4) injury treated with 3D-printed tubes composed of chitosan and alginate. The procedures were performed, blood was collected, and the rats were sacrificed after two months. Weekly checks for infection, scar healing, and motor responses were performed. Results: Rats with nerve conduits showed less macroscopic scarring. Weekly assessments of motor nerve recovery showed no movement restrictions in limbs treated with PLA conduits, graft conduits, or conduits bridging retracted nerve stumps, based on responses to stimulus checks. An infection developed in the sciatic nerve and surrounding muscle tissue of one rat with a bio-graft conduit, prompting histopathological examination to investigate its cause. Conclusions: This proof-of-principle study demonstrates the feasibility of using 3D-printed biocompatible nerve conduits for peripheral nerve repair, providing a basis for future, more comprehensive investigations. Full article

The reconstruction of a severely resorbed alveolar bone is a significant challenge in dental implantology and maxillofacial surgery. Traditional bone grafting materials, including autogenous, allogeneic, xenogeneic, and alloplastic materials, have limitations such as donor site morbidity, limited availability, and prolonged maturation periods. To address these challenges, recombinant human bone morphogenetic protein-2 (rhBMP-2) has emerged as a potent osteoinductive factor that facilitates bone regeneration without the need for additional donor site surgery. This study introduces a box technique which combines rhBMP-2 (CowellBMP^®, Cowellmedi, Busan, Republic of Korea) with a 3D-preformed titanium mesh (3D-PFTM), utilizing a mixture of allografts and xenografts for horizontal and vertical alveolar ridge augmentation. The technique leverages the structural stability provided by the OssBuilder^® (Osstem, Seoul, Republic of Korea), a preformed titanium mesh, that allows for simultaneous implant placement and vertical ridge augmentation. This technique not only reduces the treatment time compared to traditional methods but also minimizes post-operative discomfort by eliminating the need for autogenous bone harvesting. Clinical outcomes from this technique demonstrate successful bone regeneration within a shorter period than previously reported techniques, with excellent bone quality and implant stability being observed just four months after vertical augmentation. In conclusion, the so called BOXAM (BMP-2, Oss-builder, Xenograft, Allograft, Maintenance) technique presents a promising therapeutic strategy for alveolar bone reconstruction, particularly in cases of severe bone resorption. Further studies are needed to evaluate the long-term outcomes and potential limitations of this approach, especially in scenarios where the inferior alveolar nerve proximity poses challenges for fixture placement. Full article

Schwann cells (SCs) play a crucial role in peripheral nerve repair by supporting axonal regeneration and remyelination. While extensive research has been conducted using rodent SCs, increasing attention is being directed toward human SCs due to species-specific differences in phenotypical and functional properties, and accessibility of human SCs derived from diverse sources. A major challenge in translating SC-based therapies for nerve repair lies in the inability to replicate human SC myelination in vitro, posing a significant obstacle to drug discovery and preclinical research. In this study, we compared the myelination capacity of human, rodent, and porcine SCs in various co-culture conditions, including species-matched and cross-species neuronal environments in a serum-free medium. Our results confirmed that rodent and porcine SCs readily myelinate neurites under standard culture conditions after treatment with ascorbic acid for two weeks, whereas human SCs, at least within the four-week observation period, failed to show myelin staining in all co-cultures. Furthermore, we investigated whether cell culture manipulation impairs human SC myelination by transplanting freshly harvested and predegenerated human nerve segments into NOD-SCID mice for four weeks. Despite supporting host axonal regeneration into the grafts, human SCs exhibited very limited myelination, suggesting an intrinsic species-specific restriction rather than a cell culture-induced defect. These observations suggest fundamental differences between human and rodent SCs and highlight the need for human-specific models and protocols to advance our understanding of SC myelination. Full article

Background: Incomplete eyelid closure and lagophthalmos due to facial nerve palsy are significant functional and aesthetic concerns often requiring surgical correction. The aim of this systematic review is to quantitatively assess the efficacy, safety, and patient satisfaction associated with gold or platinum weight implantation, autologous fat grafting (lipofilling), and müllerectomy. Methods: A systematic review was performed following PRISMA guidelines, searching PubMed, Embase, Cochrane Library, Web of Science, and Scopus up to March 2025. Studies included clinical data on surgical correction for incomplete eyelid closure in facial palsy, reporting functional, anatomical, and satisfaction outcomes. Quality was assessed using the Newcastle–Ottawa Scale (NOS) and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: Twenty-six studies including a total of 1205 patients were included. Gold/platinum weight implantation achieved complete or near-complete eyelid closure in 83–92% of cases, with a reduction in lagophthalmos to <1 mm. Complication rates ranged from 5–15% (mainly extrusion/migration), and patient satisfaction averaged 7.9/10. Lipofilling showed persistent benefit in 77% of cases, with 9–20% requiring repeat procedures and 10–12% experiencing minor complications. Müllerectomy yielded symptomatic improvement or resolution in 92% of cases, with a mean lagophthalmos reduction of 1.18 mm. Conclusions: Gold or platinum weight implantation provides the most reliable improvement for severe upper eyelid dysfunction in facial palsy. Lipofilling is a viable autologous alternative, while müllerectomy is effective in selected cases. Further prospective comparative trials are needed to refine surgical selection and optimize outcomes. Full article

Peripheral nerve injuries (PNIs) present a significant clinical challenge due to the inherently limited regenerative capacity of the adult nervous system. Conventional therapeutic strategies, such as nerve autografting and systemic pharmacological interventions, are often limited by donor site morbidity, restricted graft availability, and suboptimal drug bioavailability. In this context, gelatin-based hydrogels have emerged as a promising class of biomaterials due to their excellent biocompatibility, biodegradability, and structural similarity to the native extracellular matrix. These hydrogels could offer a highly tunable platform capable of supporting cellular adhesion, promoting axonal elongation, and enabling localized and sustained release of therapeutic agents. This narrative review synthesizes recent advances in the application of gelatin-based hydrogels for peripheral nerve regeneration, with a particular focus on their use as delivery vehicles for neurotrophic factors, stem cells, and pharmacologically active compounds. Additionally, this review provides a foundation for extending our ongoing preclinical study, evaluating the neuroregenerative effects of alpha-lipoic acid, B-complex vitamins, and a deproteinized hemoderivative in a murine PNI model. Although systemic administration has demonstrated promising neuroprotective effects, limitations related to local drug availability and off-target exposure highlight the need for site-specific delivery strategies. In this regard, gelatin hydrogels might represent an excellent candidate for localized, controlled drug delivery. The review concludes by discussing formulation techniques, manufacturing considerations, biological performance, and key translational and regulatory aspects. Full article

Chronic pain affects a significant portion of the population, with fewer than 30% achieving adequate relief from existing treatments. This study describes the humanization methodology and characterization of an effective non-opioid single-chain fragment variable (scFv) biologic that reverses pain-related behaviors, in this case by targeting P2X4. After nerve injury, ATP release activates/upregulates P2X4 receptors (P2X4R) sequestered in late endosomes, triggering a cascade of chronic pain-related events. Nine humanized scFv (hscFv) variants targeting a specific extracellular 13-amino-acid peptide fragment of human P2X4R were generated via CDR grafting. ELISA analysis revealed nanomolar binding affinities, with most humanized molecules exhibiting comparable or superior affinity compared to the original murine antibody. Octet measurements confirmed that the lead, HC3-LC3, exhibited nanomolar binding kinetics (KD = 2.5 × 10⁻⁹ M). In vivo functional validation with P2X4R hscFv reversed nerve injury-induced chronic pain-related behaviors with a single dose (0.4 mg/kg, intraperitoneal) within two weeks. The return to naïve baseline remained durably reduced > 100 days. In independent confirmation, the spared nerve injury (SNI) model was similarly reduced. This constitutes an original method whereby durable reversals of chronic nerve injury pain, anxiety and depression measures are accomplished. Full article

Several postmastectomy breast reconstruction techniques and procedures have been implemented, although with limited evaluation of benefits and adverse effects. We conducted a systematic review on the plane and timing of reconstruction, and on the use of nipple-sparing mastectomy, acellular dermal matrix, and autologous fat grafting as the evidence base for an updated clinical practice guideline on breast reconstruction for Ontario Health (Cancer Care Ontario). Both immediate and delayed reconstruction may be considered, with preferred timing depending on factors such as patient preferences, type of mastectomy, skin perfusion, comorbidities, pre-mastectomy breast size, and desired reconstructive breast size. Immediate reconstruction may provide greater psychological or quality of life benefits. In patients who are candidates for skin-sparing mastectomy and without clinical, radiological, and pathological indications of nipple-areolar complex involvement, nipple-sparing mastectomy is recommended provided it is technically feasible and acceptable aesthetic results can be achieved. Surgical factors including incision location are important to reduce necrosis by preserving blood supply and to minimize nerve damage. There is a role for both prepectoral and subpectoral implants; risks and benefits will vary, and decisions should be made during consultation between the patient and surgeons. In patients who are suitable candidates for implant reconstruction and have adequate mastectomy flap thickness and vascularity, prepectoral implants should be considered. Acellular dermal matrix (ADM) has led to an increased use of prepectoral reconstruction. ADM should not be used in case of poor mastectomy flap perfusion/ischemia that would otherwise be considered unsuitable for prepectoral reconstruction. Care should be taken in the selection and handling of acellular dermal matrix (ADM) to minimize risks of infection and seroma. Limited data from small studies suggest that prepectoral reconstruction without ADM may be feasible in some patients. Autologous fat grafting is recommended as a treatment for contour irregularities, rippling following implant-based reconstruction, and to improve tissue quality of the mastectomy flap after radiotherapy. Full article

Background: Tooth loss significantly impacts the quality of life for adults. Inferior alveolar nerve (IAN) repositioning has garnered interest as a treatment for facilitating dental implant placement in the severely atrophic posterior mandible. However, there remains a need for standardization and classification of these techniques to improve outcomes. This study aims to propose a new clinical classification system for IAN repositioning procedures based on anatomical and procedural parameters. Methods: This study retrospectively analyzed preoperative radiographic records and surgical procedure documents over a 15-year period (2008–2023) for patients who underwent implant placement combined with IAN repositioning in the posterior atrophic mandible. Cases were classified into four categories according to bone availability, nerve location, and type of surgical intervention. Results: The study analyzed 142 edentulous posterior mandibles in 105 patients (77 women, 28 men; age range: 20–75). The cases were divided into four categories: Category 1 (58 patients, 78 sites), treated with one surgery; Category 2 (15 patients, 15 sites), treated in two stages; Category 3 (20 patients, 25 sites); and Category 4 (12 patients, 24 sites), with Categories 3 and 4 treated in a single surgery. Across all 132 sites, 411 dental implants were placed and restored with implant-supported fixed prostheses. Conclusions: This proposed classification provides a structured systematic framework for assessing and planning IAN repositioning procedures. It facilitates better diagnosis, treatment planning, and prediction of surgical stages in patients needing IAN repositioning for dental implant placement. Full article

A platform of two-component cross-linked hydrogel (cGEL) based on gelatinous peptides and anhydride-containing cross-linkers (oPNMA, oPDMA) is extended for use in peripheral nerve regeneration. Hybrid composites with bio-/chemical cues for enhanced biophysical and biochemical properties were fabricated by covalently grafting small molecular, heterobifunctional amines including the nerve growth factor mimetic LM11A-31 to the oligomeric cross-linkers prior to hydrogel formation. The cytocompatibility and growth-supportive conditions within the matrix are confirmed for pristine and modified hydrogels using L929 mouse fibroblasts and human adipose-derived stem cells (hASCs). For hASCs, cell behavior depends on the type of cross-linker and integrated amine. In a subsequent step, neonatal rat Schwann cells (SCs) are seeded on pristine and functionalized cGEL to investigate the materials’ capabilities to support SC growth and morphology. Within all formulations, cell viability, adherence, and cell extension are maintained though the cell elongation and orientation vary compared to the two-dimensional control. It is possible to merge adjustable two-component hydrogels with amines as biochemical signals, leading to improved nervous cell proliferation and activity. This indicates the potential of tunable bioactive cGEL as biomaterials in nerve implants, suggesting their use as a foundational component for nerve conduits. Full article

Background: Neuralgic amyotrophy (NA), also known as Parsonage–Turner syndrome, brachial neuritis, and idiopathic brachial plexopathy, is a rare and potentially debilitating peripheral nerve disorder characterized by acute-onset shoulder pain followed by progressive motor deficits. It is often under-recognized, with an estimated incidence of 1 to 3 per 100,000 annually, though some studies suggest the actual prevalence may be significantly higher. The condition typically progresses through three phases, an acute painful phase, a phase of weakness, and a recovery phase, with sensory disturbances common in addition to motor weakness. The exact pathogenesis of NA remains unclear, though it is thought to involve a combination of genetic, environmental, and immunological factors. While neurologic complications following hematopoietic stem cell transplantation (HSCT), such as neuropathies and myopathies, have been documented, NA remains exceedingly rare in this context, with only a few reported cases. The pathophysiology in HSCT patients is hypothesized to involve immune dysregulation, graft-versus-host disease (GvHD), infection, and the effects of immunosuppressive therapy. Diagnosis is primarily clinical, supported by electrodiagnostic studies and MRI, though no laboratory markers exist. The management of NA is largely supportive and multimodal, focusing on pain control and rehabilitation. Objectives: The objective of this study was to describe the characteristics, clinical course, and outcomes of patients admitted for HSCT who were subsequently diagnosed with NA. Study Design: This retrospective case series from a single institution examined nine (N = 9) patients who developed acute shoulder pain following HSCT. We collected data on demographics, transplant details, clinical features, MRI findings, and electrodiagnostic studies, summarized using descriptive statistics. The diagnosis of neurologic amyotrophy was based on clinical presentation and corroborated by imaging and electrodiagnostic results. Long-term follow-up was assessed to evaluate symptom recovery. Results: Between August 2020 and July 2022, nine patients (44% male, median age 60) were diagnosed with NA following autologous (n = 4) or allogeneic (n = 5) HSCT. The onset of severe shoulder pain occurred at a median of 9 days post-transplant (range 1–21 days), with the majority of patients experiencing unilateral pain, predominantly affecting the right shoulder (55%). Neurologic weakness developed on average 5.1 days after pain onset, and sensory deficits were observed in all but one patient. MRI findings revealed muscle edema, atrophy, and enhancement in six patients, while electromyography confirmed NA in five. Due to the small sample size, statistical analyses, including p-values, confidence intervals, and trend comparisons, were not performed, and thus no conclusions can be drawn regarding associations between variables such as early onset and worse outcomes. Shoulder pain resolved after a median of 23 days (range 8–40 days). Long-term follow-up (>1 year) showed that three patients achieved full or near-full recovery, four partially recovered, and two showed minimal improvement. Conclusions: NA should be highly suspected in patients with acute shoulder pain and neurologic symptoms post-HSCT. To improve diagnostic accuracy and clinical outcomes, we recommend enhanced clinician awareness, the implementation of targeted diagnostic protocols (such as MRI and electrodiagnostic studies), and the establishment of standardized long-term follow-up protocols. Full article

Peripheral nerve injuries (PNIs) commonly result from trauma, compression, or iatrogenic causes, leading to functional deficits. Despite the peripheral nervous system’s regenerative capacity, current treatments yield inconsistent outcomes. Basic science and translational research supporting nerve repair remain underdeveloped, partly due to the absence of standardized protocols, limiting reproducibility. Animal models are essential for studying injury mechanisms, repair strategies, and therapeutic development. This review examines commonly used animal models in PNI research, from non-mammalian species to rodents and large mammals. We discuss the relevance of injury types, experimental variables (i.e., age, sex, nerve type), and study design elements (i.e., nerve gap size, injury induction methods). Assessing these models’ strengths and limitations, this review aims to guide researchers in selecting appropriate models that enhance preclinical relevance. It also addresses the need for standardized protocols and future directions for improving PNI research and patient outcomes. Various PNI treatments—including microsurgery, nerve grafts, scaffolds, stem cells, immunomodulators, nerve augmentation strategies, and polyethylene glycol-mediated fusion—have been developed using animal models. These models are essential for driving innovation and translating emerging therapies to improve outcomes across a broad range of peripheral nerve injuries. Full article

Kidney transplantation significantly improves outcomes in patients with end-stage renal disease; however, postoperative complications remain a substantial concern. This review summarizes the incidence, risk factors, and management strategies for common complications after kidney transplantation. Reported incidence varies widely due to differences in definitions, diagnostic methods, and study designs. Ureteral stenosis occurs in 2.8–18.0% of recipients, vesicoureteral reflux in 0.5–86%, and urinary leakage in 1.1–7.2%. Lymphatic complications, including lymphocele and lymphorrhea, range from 0.6% to 35.2%, with one-third of complications requiring intervention. The incidence of urinary tract infections ranges from 20 to 43%, while asymptomatic bacteriuria is reported in up to 53% of recipients. Surgical site infections have a median incidence of 3.7%, and incisional hernias develop in 2.5–10% of cases, depending on follow-up duration. Vascular complications affect approximately 10% of recipients, with renal artery stenosis and thrombosis being the most prevalent. Neurologic complications, such as femoral nerve palsy and immunosuppression-related neurotoxicity, though less frequent, can impair recovery. Management strategies vary depending on severity, ranging from observation to surgical intervention. Preventive measures—including optimized ureteral stenting protocols, early catheter removal, careful immunosuppression, and appropriate antimicrobial use—play a crucial role in reducing complication risk. Despite advances in transplantation techniques and perioperative care, these complications continue to affect graft survival and patient outcomes. Further research is needed to standardize definitions and establish evidence-based protocols. Full article

Background and Objectives: In coronary artery bypass grafting (CABG) surgeries, monitoring intracranial pressure (ICP) is crucial due to neurological risks. Although pulsatile flow (PF) during cardiopulmonary bypass (CPB) is considered more physiological than non-pulsatile flow (NPF), its impact on ICP remains unclear. This study aimed to compare preoperative and postoperative optic nerve sheath diameter (ONSD) measurements between PF and NPF techniques to evaluate their effect on ICP changes. Materials and Methods: Sixty patients undergoing elective CABG (aged 45–75 years, ASA II-III-IV) were enrolled and divided into two groups depending on the cardiopulmonary bypass technique determined by the surgeon: PF (Group P, n = 30) and NPF (Group NP, n = 30). ONSD measurements were performed with ultrasound before surgery (Tpreop) and after surgery (Tpostop). Hemodynamic parameters and jugular and carotid vessel diameters were also recorded. Statistical analysis included t-tests, Mann–Whitney U-tests, chi-square tests, and Pearson correlation. Results: Both groups demonstrated significant increases in ONSD postoperatively compared to preoperative values (p < 0.001). However, no statistically significant difference in the magnitude of ONSD change was observed between the PF and NPF groups (p > 0.05). Group P showed lower ejection fractions and higher total inotrope requirements compared to Group NP (p < 0.01), but these factors did not translate into differences in postoperative ICP dynamics. Conclusions: ONSD measurements increased significantly after CABG surgery, regardless of perfusion type. PF and NPF strategies were comparable in terms of their effects on ICP as reflected by ONSD changes. ONSD ultrasonography appears to be a simple, rapid, and non-invasive tool for perioperative ICP monitoring in cardiac surgery. Further studies are needed to confirm these findings with dynamic intraoperative monitoring and neurocognitive assessments. Full article