Guanglin Wang

Critical peripheral nerve deficiencies present as one of the most formidable conundrums in the realm of clinical medicine, frequently culminating in structural degradation and derangement of the neuromuscular apparatus. Engineered extracellular vesicles (EVs) exhibit the potential to ameliorate nerve impairments. However, the advent of Wallerian degeneration (WD), an inexorable phenomenon that ensues post peripheral nerve injury, serves as an insurmountable impediment to the direct therapeutic efficacy of EVs. In this investigation, we have fashioned a dynamic network for the conveyance of PTEN-induced kinase 1 (PINK1) mRNA (E-EV-P@HPCEP) using an adaptive hydrogel with reactive oxygen species (ROS)/Ca²⁺ responsive ability as the vehicle, bearing dual-targeted, engineered EVs. This intricate system is to precisely deliver PINK1 to senescent Schwann cells (SCs) while concurrently orchestrating a transformation in the inflammatory-senescent milieu following injury, thereby stymying the progression of WD in peripheral nerve fibers through the stimulation of autophagy within the mitochondria of the injured cells and the maintenance of mitochondrial mass equilibrium. WD, conventionally regarded as an inexorable process, E-EV-P@HPCEP achieved functionalized EV targeting, orchestrating a dual-response dynamic release mechanism via boronate ester bonds and calcium chelation, effectuating an enhancement in the inflammatory-senescent microenvironment, which expedites the therapeutic management of nerve deficiencies and augments the overall reparative outcome.

Peripheral nerve deficits give rise to motor and sensory impairments within the limb. The clinical restoration of extensive segmental nerve defects through autologous nerve transplantation often encounters challenges such as axonal mismatch and suboptimal functional recovery. These issues may stem from the limited regenerative capacity of proximal axons and the subsequent Wallerian degeneration of distal axons. To achieve the integration of sensory and motor functions, a spatially differential plasmid DNA (pDNA) dual‐delivery nanohydrogel conduit scaffold is devised. This innovative scaffold facilitates the localized administration of the transforming growth factor β (TGF‐β) gene in the proximal region to accelerate nerve regeneration, while simultaneously delivering nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) to the distal region to mitigate Wallerian degeneration. By promoting autonomous and selective alignment of nerve fiber gap sutures via structure design, the approach aims to achieve a harmonious unification of nerve regeneration, neuromotor function, and sensory recovery. It is anticipated that this groundbreaking technology will establish a robust platform for gene delivery in tissue engineering.

Metallic ions have been widely investigated and incorporated into bone substitutes for bone regeneration owing to their superior capacity to induce angiogenesis and osteogenesis. Exosomes are key paracrine mediators that play a crucial role in cell-to-cell communication. However, the role of exosomes in metallic ion-induced bone formation and their underlying mechanisms remain unclear. Thus, this review systematically analyzes the effects of metallic ions and metallic ion-incorporated biomaterials on exosome secretion from mesenchymal stem cells (MSCs) and macrophages, as well as the effects of secreted exosomes on inflammation, angiogenesis, and osteogenesis. In addition, possible signaling pathways involved in metallic ion-mediated exosomes, followed by bone regeneration, are discussed. Despite limited investigation, metallic ions have been confirmed to regulate exosome production and function, affecting immune response, angiogenesis, and osteogenesis. Although the underlying mechanism is not yet clear, these insights enrich our understanding of the mechanisms of the metallic ion-induced microenvironment for bone regeneration, benefiting the design of metallic ion-incorporated implants.

Background: The use of a tourniquet during high tibial osteotomy (HTO) is a routine procedure, but there is currently no research on the benefits and potential risks of tourniquet use during HTO. The aim of this study was to investigate the impact of tourniquet on perioperative blood loss, early functional recovery and complications in opening wedge HTO with modern tranexamic acid protocols. Methods: This was a retrospective cohort study of patients who underwent unilateral opening wedge HTO between January 2019 and September 2020. All patients were divided into two groups according to whether a tourniquet was applied during HTO. Patients in both groups received the same surgical procedures, tranexamic acid protocols and other perioperative treatments. Preoperative baseline data, intraoperative data, early postoperative recovery and all complications during the 3-month follow-up were collected and compared between the two groups. Results: A total of 62 patients were enrolled in this study, including 32 in the tourniquet group and 30 in the non-tourniquet group. There was no significant difference in preoperative baseline data between the two groups (P > 0.05 in all). Intraoperative blood loss in the tourniquet group was significantly lower than that in the non-tourniquet group (80.22 ml versus 94.00 ml, P < 0.001), but there was no difference in total blood loss (187.39 ml versus 193.31 ml, P = 0.714). And no patient in either group required blood transfusion. In terms of early postoperative recovery, tourniquet use significantly increased pain scores and reduced knee range of motion on the first and second postoperative days, but there was no significant difference between the two groups at postoperative third day and third month. Furthermore, there was no significant difference between the two groups in terms of lower limb force line correction, length of stay, Knee Society Score or the incidence of complications during the 3-month follow-up (P > 0.05 in all). Conclusions: In opening wedge HTO with modern tranexamic acid protocols, not using a tourniquet does not increase perioperative total blood loss or the risk of complications, but facilitates early postoperative recovery by reducing pain and increasing range of motion.

Background: The femoral neck system (FNS) may be a valid alternative for treating femoral neck fractures, but few studies have compared the outcomes between FNS and cannulated cancellous screws. This study aimed to compare the clinical efficacy and complications of FNS with those of inverted cannulated cancellous screws (ICCS) for the treatment of femoral neck fractures in adults.Methods: This retrospective study evaluated patients with femoral neck fractures who underwent FNS or ICCS internal fixation between June 2019 and January 2020. The operative time, intraoperative blood loss, number of fluoroscopies, length of surgical incision, length of hospital stay, time to fracture healing, and other indicators were compared between the two groups. The incidence of complications such as nonunion, avascular necrosis of the femoral head, loosening of the internal fixation, and shortening of the femoral neck during follow-up was also assessed in both groups.Results: Among the 92 patients included, 47 and 45 patients were categorized into the FNS and ICCS groups, respectively. Follow-up ranged from 14 to 24 months. There were no significant between-group differences in sex, age, side of the injured limb, and type of fracture and in operative time, intraoperative blood loss, incision length, and length of hospital stay (allP> 0.05). The incidence of complications such as fracture nonunion, avascular necrosis of the femoral head, and screw loosening was also comparable between the two groups. However, the number of fluoroscopies was significantly lower in the FNS group than in the ICCS group (P< 0.05). The fracture healing time was also significantly lower in the FNS group than in the ICCS group (P< 0.05). Furthermore, the femoral neck shortening and Harris hip score at the last follow-up were significantly better in the FNS group than in the ICCS group (P< 0.05).Conclusions: FNS for femoral neck fractures improves hip functional recovery and reduces the femoral neck shortening rate and fluoroscopy exposure postoperatively. Thus, FNS can be an alternative to ICCS for the treatment of femoral neck fractures.