Biological macromolecule-derived matrices and biomimetic delivery interfaces can convert artificial nerve conduits from passive bridges into locally regulatory repair platforms. Long-gap peripheral nerve defects remain difficult to repair because the defect region must rapidly rebuild a vascularized, cytoprotective, and cell-permissive microenvironment for Schwann cell survival, axonal extension, and remyelination. Here, we developed a Gelatin Methacryloyl (GelMA)-based biomimetic melatonin/vascular endothelial growth factor (VEGF)-encoding plasmid DNA (pVEGF) Polycaprolactone (PCL)/GelMA nerve conduit incorporating macrophage membrane-coated nanoparticles (MNPs). In this hierarchical design, PCL provided structural support, GelMA formed a gelatin-derived intraluminal hydrogel matrix, and MNPs served as the integrated melatonin/pVEGF delivery module. The nanoparticles showed stable assembly, sustained dual-cargo release, and retention of macrophage membrane-associated proteins. In vitro, the system enhanced VEGF expression, promoted endothelial migration and tube formation, reduced oxidative stress, and protected Schwann cells under oxidative injury. In a rat 15-mm sciatic nerve defect model, the PCL-G@MNPs conduit improved early vascular reconstruction, axon/Schwann cell-associated tissue regeneration, remyelination, electrophysiological recovery, target muscle preservation, and sensory-motor functional outcomes compared with control conduits. Bulk RNA sequencing (RNA-seq) further identified early enrichment of antioxidant-response, hypoxia-inducible factor-1 (HIF-1)/VEGF-related angiogenic, extracellular matrix/cell-adhesion, and neurotrophic programs. These molecular changes were observed together with later structural and functional improvements, although the temporal and causal relationships among redox regulation, vascular remodeling, neural regeneration, and functional recovery were not directly established. These findings support the integration of biological macromolecular matrices, membrane-biomimetic interfaces, and nucleic-acid delivery as a redox-angiogenic microenvironmental priming strategy for long-gap peripheral nerve repair.

Bone defects remain a substantial clinical burden. Exosomes have been extensively investigated as cell-free therapeutic candidates, exhibiting favorable biocompatibility and potential applicability in bone defect repair. Mechanisms relevant to bone regeneration are delineated, including activation of osteogenic and angiogenic programs, modulation of osteoblast–osteoclast coupling, immune regulation, and extracellular matrix remodeling. Engineering strategies that enhance targeting, stability, and potency are summarized. Delivery platforms that provide spatial and temporal control of release at defect sites are also appraised. Artificial intelligence (AI) has been examined as an accelerator of translation. Applications include high‑fidelity exosome characterization, data‑driven biomaterial and formulation design, and prediction of therapeutic response from multimodal data. Large language models further assist evidence synthesis and hypothesis generation. Persistent barriers include heterogeneity in isolation and analytics, low yield and limited scalability, lack of standardization, and insufficient validation in disease‑relevant and large‑animal models. A forward agenda emphasizes standardized manufacturing and quality control, mechanism‑informed cargo and surface engineering, responsive delivery systems and AI‑enabled design–control pipelines to realize precise and reproducible exosome therapies for complex bone defects.

[This corrects the article on p. 2343 in vol. 8, PMID: 26045741.].

BACKGROUND: Peripheral nerve injuries compromise sensory and motor functions, severely affecting patients' quality of life. Early lipid peroxidation drives oxidative stress, disrupting the regenerative microenvironment. Hyaluronic acid (HA), an essential extracellular matrix component, shows promise in mitigating oxidative damage and fostering repair. METHODS: In a rat sciatic nerve crush model, HA hydrogel was applied to enhance retention at the injury site. Transcriptomic analysis at 24 hours postinjury identified key pathways. In vitro assays examined HA's protective effects on Schwann cells against lipid peroxidation and oxidative stress. In vivo, HA hydrogel was administered immediately (0 hour) postcrush, followed by 4-methylumbelliferonee induced inhibition of endogenous HA synthesis and exogenous HA supplementation to clarify HA's role. RESULTS: HA treatment reduced early lipid peroxidation, upregulated glutathione metabolism, and stimulated extracellular matrix receptor interactions, notably elevating CD44 expression. In vitro, HA lowered oxidative stress and maintained Schwann cell viability. In vivo, early HA intervention mitigated muscle atrophy, preserved myelin sheaths, and improved Sciatic Functional Index scores compared to delayed or untreated controls. Inhibiting endogenous HA synthesis impaired recovery, which was partially reversed by exogenous HA. CONCLUSIONS: Early HA intervention modulates lipid peroxidation and oxidative stress via the HA/CD44 axis, establishing a supportive microenvironment for peripheral nerve regeneration and functional recovery. These findings underscore the potential of HA-based strategies to curb early lipid peroxidation, thereby expediting nerve repair and accelerating regeneration.

Chronic wounds are frequently complicated by bacterial biofilms, in which the extracellular polymeric substance (EPS) significantly impedes drug penetration and diminishes therapeutic efficacy. To overcome this limitation, we designed an innovative "asymmetric" Janus-structured bilayer microneedle (MN) system, termed SPG-PH MNs, which integrates a sodium alginate/polyacrylamide/guar gum (SPG) hydrogel backing with a polyvinyl alcohol/hyaluronic acid (PH) bilayer MN layer. Upon penetration into the biofilm, the polyvinyl alcohol (PVA) tip layer enables sustained release of α-amylase (α-Amy) for enzymatic EPS degradation and tannic acid (TA) for anti-inflammatory activity. Simultaneously, the rapidly dissolving hyaluronic acid (HA) base layer delivers 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra(p-toluenesulfonate) (TMPyP) and L-arginine (L-Arg) directly to bacterial colonies within the EPS. This co-delivery facilitates synergistic antibacterial therapy via combined photodynamic therapy (PDT) and nitric oxide (NO) gas generation under near-infrared (NIR) irradiation. Following treatment, the sodium alginate/polyacrylamide/guar gum backing hydrogel forms a flexible and adhesive physical barrier that helps prevent secondary infection. Both in vitro and in vivo studies validated the feasibility and efficacy of this integrated strategy, achieving a wound closure ratio of 99.26 % within 11 days in a biofilm-infected mouse model. The proposed multifunctional platform thus demonstrates strong potential for effective eradication of wound-infecting biofilms and promotion of tissue regeneration.

The healing of diabetic wounds is collectively impeded by the complex pathological environment, acute oxidative stress, and chronic inflammation, where uncontrolled bleeding and elevated glucose levels seriously impaired healing process. Although considerable efforts have been devoted to addressing these issues, treatment of diabetic wounds remains a major clinical obstacle. Herein, an injectable glucose-responsive hydrogel is developed to promote diabetic wound repair. The gelatin is functionalized with cystamine and phenylboronic acid (PBA) to enhance loading capacity of Prussian blue (PB) and enable stimuli-responsive behavior to glucose fluctuations in the wound environment, while the incorporation of oxidized dextran (OD) further improves the robust adhesion onto diabetic wounds. The resulting hydrogel (ODpCG-PB) exhibits shape adaptability, robust adhesion, self-healing ability and glucose responsiveness. It also presents excellent radical scavenging efficiency and macrophage polarization toward anti-inflammatory M2 phenotype to mitigate oxidative stress, attenuate inflammatory response and enhance angiogenesis. A significant improved hemostatic efficacy of ODpCG-PB surpasses clinically used fibrin glue in liver, femoral artery, and cardiac injury models. Remarkably, this all-in-one ODpCG-PB can accelerate wound closure via promoting re-epithelialization and collagen deposition in a diabetic skin defect model. Overall, this work provides a new design of dressing toward an effective healing of diabetic wound.

This paper comprehensively perfects the sensitive node transient detection feedback latch (SNTDFL) technique, subsequently conceptualizes an ideal hardening structure for the pre-amplification stage, and proposes a radiation hardened by design (RHBD) strategy to cope with the severe single-event transient (SET) effects of high-precision voltage comparators in a space radiation environment. Analysis and verification results show that the hardening strategy exhibits excellent SET hardening performance, which can not only detect extremely small transient voltage disturbances at sensitive nodes but also effectively resist transient current pulses of various intensities generated by SETs. Compared with an unhardened high-precision comparator, the proposed one, hardened with a hybrid strategy of SNTDFL and triple modular redundancy (TMR) techniques, can greatly preserve the original electrical properties and remarkably improve the tolerance of SET with little overhead. In addition, the proposed high-precision comparator significantly reduces static power consumption compared with the one hardened with the TMR technique alone and has a smaller area overhead. This paper comprehensively perfects the sensitive node transient detection feedback latch (SNTDFL) technique, conceptualizes an ideal hardening structure for the pre-amplification stage, and proposes a high-precision comparator hardened with a hybrid strategy of SNTDFL and triple modular redundancy (TMR) techniques. This strategy not only greatly preserves the electrical characteristics but also detects extremely small transient voltage disturbances caused at sensitive nodes and effectively resists transient current pulses of various intensities, remarkably improving the comparator's tolerance to SET. image

In this study, we developed a hollow aerogel fiber out of reduced graphene oxide (rGO), with a hierarchically ordered microstructure through a three-dimensional coaxial printing methodology, that enabled a physicochemically cooperative construction process at multiscale. The rGO hollow aerogel fiber was modified by depositing polycaprolactone (PCL) and melatonin (Mel). Attributable to its elaborately designed hierarchical structure and arched alignment of two-dimensional micro-sheets, the rGO/PCL/Mel hybrid aerogel bio-fiber demonstrated remarkable structural robustness in maintaining ordered pathways and high porosity (98.5

Autografting is the gold standard for surgical repair of nerve defects > 5 mm in length; however, autografting is associated with potential complications at the nerve donor site. As an alternative, nerve guidance conduits may be used. The ideal conduit should be flexible, resistant to kinks and lumen collapse, and provide physical cues to guide nerve regeneration. We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them. Subsequently, we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen. The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers. The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability. Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model, suggesting that it has potential for clinical use in human nerve injuries.

To reduce the impact of the single-event transient (SET) effect on the high-precision comparator, based on the common high-gain pre-amplification stage structure of the comparator, a new radiation hardened by design (RHBD) method, namely, the sensitive node transient detection feedback latch (SNTDFL) technique, is proposed. The hardening technique avoids comparator erroneous output by detecting the sensitive nodes of the high-gain pre-amplification stage. The detection circuit receives the response generated by the high energy particle impacts and feeds the high level back to the sensitive nodes to latch the current comparator state. In this paper, a novel high-precision SET hardened voltage comparator based on this technique is developed. Through detailed circuit principle and simulation analysis, the functional characteristics and the hardening performance of the high-precision hardened comparator are verified. Compared with the unhardened and the TMR technique hardened comparator, the SNTDFL technique hardened comparator effectively avoids the erroneous output caused by the SET effect with less overhead and still has excellent functional characteristics.

Abstract The inevitable secondary victimization of patients during the grafting of autogenous nerve necessitates the urgent development of bioactive conduits for the precise repair of peripheral nerve (PN) defects. However, the limited selection of appropriate components and inferior structural designs of many porous scaffolds have hindered satisfactory PN regeneration. In this study, we created a 3D hollow conduit of reduced graphene oxide (rGO) with a hierarchically ordered microstructure through a coaxial printing methodology that enabled a physicochemically cooperative construction process at multiscale. We deposited a mixture of polycaprolactone (PCL) and melatonin (Mel) as the biologically enhancing constitution conformably over the 3D rGO templated conduit. Attributing to its elaborately designed hierarchical structure and arched alignment of 2D micro sheets, the 3D rGO/PCL/Mel hybrid bio-conduit has demonstrated remarkable structural robustness in maintaining ordered pathways and high porosity (98.5 ± 0.24%), which facilitated nerve growth in a complex survival environment in vivo. Furthermore, the excellent combination of properties such as electrical conductivity, biocompatibility, and mechanical properties (with an elastic modulus ranging from 7.06 ± 0.81 MPa to 26.58 ± 4.99 MPa), has led to highly efficient regeneration of well-ordered PN tissue. Systematic evaluations of nerve regeneration and muscle function recovery in an SD rat model with a long nerve defect (> 15 mm) have validated the virtually identical performance of the 3D rGO/PCL/Mel conduit compared to the autogenous nerve graft group. This study confirms a promising approach to clinical PN repair of long defects through the combined regulation of rational structure design on multiscale and indispensable chemical modification of rGO-based functional nerve regeneration conduits.

Summary In this paper, a highly stable and low‐cost 12T (HSLC12T) radiation hardened static‐random‐access‐memories (SRAM) cell is proposed in 55 nm CMOS technology. Based on polarity reversal design and read/write separation structure, the proposed HSLC12T cell can recover from any single event upsets (SEUs) induced at all its sensitive nodes and even single event double‐node‐upsets (SEDNUs) induced at its internal storage node pair Q‐QN, while also having the maximum read static noise margin (RSNM) and lower static hold power, as well as excellent write speed and write‐ability. Though the HSLC12T cell exhibits a larger read delay, it has the best overall performance of all other cells. This is proven by having the highest electrical quality metric (EQM) value, thus making the proposed HSLC12T cell a better choice for aerospace applications.

Spinal cord injury (SCI) is a devastating disorder that often results in severe sensorimotor function impairment with limited recovery of function. In recent years, rehabilitation training for spinal cord injury has gradually emerged, and some of them play an important role in the repair of spinal cord injury However, the optimal training regimen for SCI remains to be determined. In this study, we explore the effects of rotarod training (began at 7 days post-injury) on the recovery of motor function after SCI, as well as its possible repair mechanism from the aspects of function and histopathological changes, the behaviors of specific trophic factors and cytokines, and the expression profile of specific genes. Multiple functional assessments showed that rotarod training initiated at 7 days post-injury is unsuitable for promoting neuro-electrophysiological improvement and trunk stability, but impaired functional coordination and motor recovery. In addition, rotarod training has negative effects on spinal cord repair after SCI, which is manifested as an increase of lesion area, a decrease in neuronal viability, a deterioration in immuno-microenvironment and remyelination, a significant reduction in the expression of trophic factors and an increase in the expression of pro-inflammatory factors. RNA sequencing suggested that the genes associated with angiogenesis and synaptogenesis were significantly downregulated and the PI3K-AKT pathway was inhibited, which was detrimental to spinal cord repair and impeded nerve regeneration. These results indicate that immediate rotarod training after SCI is currently unsuitable for rehabilitation in mice.

In this paper, a high-performance and highly-stable soft error resistant 12T (HPHS12T) SRAM cell is proposed. Based on polarity reversal design and NMOS stacked structure, the proposed HPHS12T cell can recover from any single event upsets (SEU) induced at all its sensitive nodes and even single event multiple-node-upsets (SEMNU) induced at its internal storage node pair Q-QN, while also having the maximum read static noise margin (RSNM) and write noise margin (WNM), as well as excellent write-ability. Though the HPHS12T cell exhibits a larger static hold power, it has the best overall performance of all the other cells. This is proven by having the highest electrical quality metric (EQM) value, thus making the proposed cell a better choice for space applications.

Based on differential cascade voltage switch architecture, this paper proposes a level shifter with optimized energy consumption, constructed by stacking diode-connected NMOS and PMOS transistors and splitting input signals of the two output stages. Eventually, the overlap time of input signals of the two output stages has been reduced, during which there is a considerable short-current from high voltage source to ground. When implemented in a 110 nm CMOS process, post-layout netlist simulations show that the proposed level shifter exhibits a 2.31 ns switching delay and 819 fJ energy consumption when converting a 1.5 V input signal into 4.5 V with 10 MHz operational frequency and 15 fF output load.

Intramembranous ossification (IMO) and endochondral ossification (ECO) are two pathways of bone regeneration. The regeneration of most bone, such as limb bone, trunk bone, and skull base bone, mainly occurs in the form of endochondral ossification, which has also become one of the effective ways for bone tissue engineering. In this work, we prepared a well-structured and biocompatible methacrylated gelatin/polymethacrylic acid (GelMA/PMAA) hydrogel by digital light processing (DLP) printing technology, which could effectively chelate iron ions and continuously activate the hypoxia-inducible factor-1 alpha (HIF-1α) signaling pathway to promote the process of endochondral ossification and angiogenesis. The incorporation of PMAA endowed the hydrogel with remarkable viscoelasticity and high efficacy in chelation of iron ions, giving rise to the activation of HIF-1α signaling pathway, improving chondrogenic differentiation in the early stage, and facilitating vascularization in the later stage and bone remodeling. Therefore, the findings have significant implications on DLP printing technology of endochondral osteogenesis induced by the iron-chelating property of biological scaffold, which will provide an effective way in the development of novel bone regeneration.

Tissue-engineered scaffolds are an effective method for the treatment of bone defects, and their structure and function are essential for bone regeneration. Digital light processing (DLP) printing technology has been widely used in bone tissue engineering (BTE) due to its high printing resolution and gentle printing process. As commonly used bioinks, synthetic polymers such as polyethylene glycol diacrylate (PEGDA) and Pluronic F127 diacrylate (F127DA) have satisfactory printability and mechanical properties but usually lack sufficient adhesion to cells and tissues. Here, a compound BTE scaffold based on PEGDA, F127DA, and gelatin methacrylate (GelMA) was successfully prepared using DLP printing technology. The scaffold not only facilitated the adhesion and proliferation of cells, but also effectively promoted the osteogenic differentiation of mesenchymal stem cells in an osteoinductive environment. Moreover, the bone tissue volume/total tissue volume (BV/TV) of the GelMA/PEGDA/F127DA (GPF) scaffold in vivo was 49.75 ± 8.50%, higher than the value of 37.10 ± 7.27% for the PEGDA/F127DA (PF) scaffold and 20.43 ± 2.08% for the blank group. Therefore, the GPF scaffold prepared using DLP printing technology provides a new approach to the treatment of bone defects.

Tissue Engineering for Orthopaedics and Mechanobiology, Bone and Joint Program, Department for BioMedical Research (DBMR) of the Medical Faculty, University of Bern, Bern, Switzerland, Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, Medical Faculty, University of Bern, Bern, Switzerland, Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi’an, China, Department of Orthopaedics, Chinese PLA General Hospital, Beijing, China, Rush Medical College, Rush University, Chicago, IL, United States

Although autologous nerve transplantation is the gold standard for treating peripheral nerve defects, it has many clinical limitations. As an alternative, various tissue-engineered nerve grafts have been developed to substitute for autologous nerves. In this study, a novel nerve graft composed of chitin scaffolds and a small autologous nerve was used to repair sciatic nerve defects in rats. The novel nerve graft greatly facilitated regeneration of the sciatic nerve and myelin sheath, reduced atrophy of the target muscle, and effectively restored neurological function. When the epineurium of the small autogenous nerve was removed, the degree of nerve regeneration was similar to that which occurs after autogenous nerve transplantation. These findings suggest that our novel nerve graft might eventually be a new option for the construction of tissue-engineered nerve scaffolds. The study was approved by the Research Ethics Committee of Peking University People’s Hospital (approval No. 2019PHE27) on October 18, 2019.

目的 通过一例右腋窝皮脂腺囊肿患者的诊治情况,探讨皮脂腺囊肿合并感染时的临床表现、诊断、鉴别诊断及治疗,提高临床医师对皮脂腺囊肿合并感染的诊治水平.方法 某男性患者右腋窝皮脂腺囊肿伴感染于2021年4月1日入院.结合案例的具体特点,采取一系列切实可行的治疗方法.结果 患者因右腋窝皮脂腺囊肿伴感染就诊,就诊前一天囊肿部位出现流脓,呈乳白色豆腐渣样,无流血,伴明显压痛,肿物约3×2 cm大小,表面可见白头一枚,局部皮肤发红,皮温高,伴肿胀、疼痛等不适,波动感不明显.入院后给予左氧氟沙星氯化钠注射液抗感染治疗,脓肿大小未见减小.后将脓液分泌物送检二代测序,结果报告嗜胨菌及大芬戈尔德菌检出丰度极高.4月3日对脓肿部位行消毒挤压及扩创治疗,结合病例青霉素过敏史及文献中对于革兰阳性厌氧球菌的治疗策略和临床抗感染治疗经验,应用美罗培南静滴抗感染治疗,同时使用连翘膏于表面旋涂,中心油纱覆盖,脓液逐渐减少至消失,恢复顺利,无复发征象.结论 嗜胨菌和大芬戈尔德菌的临床感染病例,国内相关报道相对较少,而目前临床上尚未报道过皮脂腺囊肿合并嗜胨菌和大芬戈尔德菌感染病例.随着宏基因组学第二代测序技术的发展和临床应用的开展,对于易被临床忽视的革兰阳性厌氧球菌的认识以及快速筛查检测有所提高.