Plenty of macrophages are recruited to the injured nerve to play key roles in the immunoreaction and engulf the debris of degenerated axons and myelin during Wallerian degeneration, thus creating a conducive microenvironment for nerve regeneration. Recently, drugs targeting the RhoA pathway have been widely used to promote peripheral axonal regeneration. However, the role of RhoA in macrophage during Wallerian degeneration and nerve regeneration after peripheral nerve injury is still unknown. Herein, we come up with the hypothesis that RhoA might influence Wallerian degeneration and nerve regeneration by affecting the migration and phagocytosis of macrophages after peripheral nerve injury.Immunohistochemistry, Western blotting, H&E staining, and electrophysiology were performed to access the Wallerian degeneration and axonal regeneration after sciatic nerve transection and crush injury in the Lyz; RhoA (cKO) mice or Lyz2 (Cre) mice, regardless of sex. Macrophages' migration and phagocytosis were detected in the injured nerves and the cultured macrophages. Moreover, the expression and potential roles of ROCK and MLCK were also evaluated in the cultured macrophages.1. RhoA was specifically knocked out in macrophages of the cKO mice; 2. The segmentation of axons and myelin, the axonal regeneration, and nerve conduction in the injured nerve were significantly impeded while the myoatrophy was more severe in the cKO mice compared with those in Cre mice; 3. RhoA knockout attenuated the migration and phagocytosis of macrophages in vivo and in vitro; 4. ROCK and MLCK were downregulated in the cKO macrophages while inhibition of ROCK and MLCK could weaken the migration and phagocytosis of macrophages.Our findings suggest that RhoA depletion in macrophages exerts a detrimental effect on Wallerian degeneration and nerve regeneration, which is most likely due to the impaired migration and phagocytosis of macrophages resulted from disrupted RhoA/ROCK/MLCK pathway. Since previous research has proved RhoA inhibition in neurons was favoring for axonal regeneration, the present study reminds us of that the cellular specificity of RhoA-targeted drugs is needed to be considered in the future application for treating peripheral nerve injury.© 2021. The Author(s).

Peripheral nerve injury is a common clinical disease. Effective post-injury nerve repair remains a challenge in neurosurgery, and clinical outcomes are often unsatisfactory, resulting in social and economic burden. Particularly, the repair of long-distance nerve defects remains a challenge. The existing nerve transplantation strategies show limitations, including donor site morbidity and immune rejection issues. The multiple studies have revealed the potential of tissue engineering strategies based on biomaterials in the repair of peripheral nerve injuries. We review the events of regeneration after peripheral nerve injury, evaluates the efficacy of existing nerve grafting strategies, and delves into the progress in the construction and application strategies of different nerve guidance conduits. A spotlight is cast on the materials, technologies, seed cells, and microenvironment within these conduits to facilitate optimal nerve regeneration. Further discussion was conducted on the approve of nerve guidance conduits and potential future research directions. This study anticipates and proposes potential avenues for future research, aiming to refine existing strategies and uncover innovative approaches in biomaterial-based nerve repair. This study endeavors to synthesize the collective insights from the fields of neuroscience, materials science, and regenerative medicine, offering a multifaceted perspective on the role of biomaterials in advancing the frontiers of peripheral nerve injury treatment.© 2024 The Authors.

Injured peripheral nerves but not central nerves have the capacity to regenerate and reinnervate their target organs. After the two most severe peripheral nerve injuries of six types, crush and transection injuries, nerve fibers distal to the injury site undergo Wallerian degeneration. The denervated Schwann cells (SCs) proliferate, elongate and line the endoneurial tubes to guide and support regenerating axons. The axons emerge from the stump of the viable nerve attached to the neuronal soma. The SCs downregulate myelin-associated genes and concurrently, upregulate growth-associated genes that include neurotrophic factors as do the injured neurons. However, the gene expression is transient and progressively fails to support axon regeneration within the SC-containing endoneurial tubes. Moreover, despite some preference of regenerating motor and sensory axons to “find” their appropriate pathways, the axons fail to enter their original endoneurial tubes and to reinnervate original target organs, obstacles to functional recovery that confront nerve surgeons. Several surgical manipulations in clinical use, including nerve and tendon transfers, the potential for brief low-frequency electrical stimulation proximal to nerve repair, and local FK506 application to accelerate axon outgrowth, are encouraging as is the continuing research to elucidate the molecular basis of nerve regeneration.

Peripheral nerve injury (PNI) is a common clinical challenge, requiring timely and orderly initiation of synergistic anti-inflammatory and reparative therapy. Although the existing cascade drug delivery system can realize sequential drug release through regulation of the chemical structure of drug carriers, it is difficult to adjust the release kinetics of each drug based on the patient's condition. Therefore, there is an urgent need to develop a cascade drug delivery system that can dynamically adjust drug release and realize personalized treatment. Herein, we developed a responsive cascade drug delivery scaffold (RCDDS) which can adapt to the therapeutic time window, in which Vitamin B12 is used in early controllable release to suppress inflammation and nerve growth factor promotes regeneration by cascade loading. The RCDDS exhibited the ability to modulate the drug release kinetics by hierarchically opening polymer chains triggered by ultrasound, enabling real-time adjustment of the anti-inflammatory and neuroregenerative therapeutic time window depending on the patient's status. In the rat sciatic nerve injury model, the RCDDS group was able to achieve neural repair effects comparable to the autograft group in terms of tissue structure and motor function recovery. The development of the RCDDS provides a useful route toward an intelligent cascade drug delivery system for personalized therapy.

Visual disabilities affect more than 250 million people, with 43 million suffering from irreversible blindness. The eyes are an extension of the central nervous system which cannot regenerate. Neural tissue engineering is a potential method to cure the disease. Injectability is a desirable property for tissue engineering scaffolds which can eliminate some surgical procedures and reduce possible complications and health risks. We report the development of the anisotropic structured hydrogel scaffold created by a co-injection of cellulose nanofiber (CNF) solution and co-polypeptide solution. The positively charged poly (L-lysine)-r-poly(L-glutamic acid) with 20 mol% of glutamic acid (PLLGA) is crosslinked with negatively charged CNF while promoting cellular activity from the acid nerve stimulate. We found that CNF easily aligns under shear forces from injection and is able to form hydrogel with an ordered structure. Hydrogel is mechanically strong and able to support, guide, and stimulate neurite growth. The anisotropy of our hydrogel was quantitatively determined in situ by 2D optical microscopy and 3D X-ray tomography. The effects of PLLGA:CNF blend ratios on cell viability, neurite growth, and neuronal signaling are systematically investigated in this study. We determined the optimal blend composition for stimulating directional neurite growth yielded a 16% increase in length compared with control, reaching anisotropy of 30.30% at 10°/57.58% at 30°. Using measurements of calcium signaling in vitro, we found a 2.45-fold increase vs. control. Based on our results, we conclude this novel material and unique injection method has a high potential for application in neural tissue engineering.

Cell cultures aiming at tissue regeneration benefit from scaffolds with physiologically relevant elastic moduli to optimally trigger cell attachment, proliferation and promote differentiation, guidance and tissue maturation. Complex scaffolds designed with guiding cues can mimic the anisotropic nature of neural tissues, such as spinal cord or brain, and recall the ability of human neural progenitor cells to differentiate and align. This work introduces a cost-efficient gelatin-based submicron patterned hydrogel–fiber composite with tuned stiffness, able to support cell attachment, differentiation and alignment of neurons derived from human progenitor cells. The enzymatically crosslinked gelatin-based hydrogels were generated with stiffnesses from 8 to 80 kPa, onto which poly(ε-caprolactone) (PCL) alignment cues were electrospun such that the fibers had a preferential alignment. The fiber–hydrogel composites with a modulus of about 20 kPa showed the strongest cell attachment and highest cell proliferation, rendering them an ideal differentiation support. Differentiated neurons aligned and bundled their neurites along the aligned PCL filaments, which is unique to this cell type on a fiber–hydrogel composite. This novel scaffold relies on robust and inexpensive technology and is suitable for neural tissue engineering where directional neuron alignment is required, such as in the spinal cord.

Medical dressings are a common medical device, playing a significant role in the medical realm. It has a wide range of applications in the treatment, healing, and infection control of trauma and surgical wounds. Research has found that wounds can heal better and faster in a moist environment. Hence, an ideal medical dressing should maintain optimal moisture levels at the wound site and effectively absorb exudates. Serving as a barrier against microorganisms, medical dressings must possess robust mechanical properties, flexibility to conform to diverse wound shapes, and effective antibacterial qualities to expedite the healing process.<br>Electrospinning, a technique that utilizes a high-voltage electrostatic field to produce ultrafine fibers, has attracted much attention due to the highly similar structure of the nanofiber membrane to the natural extracellular matrix of the human body. Electrospinning usually uses natural or synthetic polymer materials as raw materials, most of which have good biocompatibility, can be compatible with human tissues, and reduce allergic reactions to patients. By modifying the membrane's surface, adjusting the electrospun material, or incorporating drugs, we can create specialized functional dressings tailored to diverse application scenarios, thus offering convenience to both medical professionals and patients Consequently, further investigation and utilization of nanofiber membrane medical dressings hold substantial clinical importance and promise for the future<br>Chitosan (CS), a multifunctional biomaterial, is renowned for its non-toxicity, biodegradability, and excellent biocompatibility. In addition, materials based on CS also have immune stimulation and antibacterial performance, and are often used in fields such as wound healing, hemostasis, tissue engineering, and medical textiles. Nonetheless, CS suffers from poor electrospinning performance and insufficient mechanical strength, often necessitating crosslinking or blending with other polymers to enhance these properties. Polyvinyl alcohol (PVA), a water-soluble polymer, is extensively employed in the biomedical field, particularly in tissue engineering and wound dressings, owing to its favorable biocompatibility and biodegradability. PVA also has excellent film-forming and fiber forming properties, making it widely used in the field of electrospinning. Glycerol (GL) is a transparent, colorless, odorless, viscous, and hygroscopic liquid produced by the hydrolysis of triGLcerides. It is often used as a wetting agent in the food industry (plasticizer, stabilizer, and emulsifier) and cosmetic formulations.<br>To meet the requirements of high hydrophilicity and antibacterial properties for medical trauma dressings, PVA/CS/GL nanofiber membranes were prepared by using CS, polyvinyl alcohol (PVA), and GL as raw materials through electrospinning technology. The morphology and structure of the nanofiber membranes were characterized, and their thermal stability, hydrophilicity, swelling degree, mechanical properties, and antibacterial properties were analyzed. The results indicated that the PVA/CS/GL nanofiber membrane exhibited optimal overall performance when the mass fraction of GL was set at 3%, featuring a well-structured network and uniform fiber diameter. The addition of GL improved the poor hydrophilicity and low mechanical strength of chitosan based nanofiber membranes. After adding GL with a mass fraction of 3%, the contact angle of the nanofiber membrane decreased from 53.3 ° to 25.3 °, and the equilibrium swelling rate in PBS buffer increased from 239.5% to 332.1%. The tensile strength and elongation at break increased from 2.68 MPa and 8.2% to 5.83 MPa and 17.9%, respectively. Antibacterial experiments showed that the antibacterial rates of PVA/CS/GL nanofiber membranes against Escherichia coli and Staphylococcus aureus were 94.39% and 89.65%, respectively, showing good antibacterial performance. Therefore, the PVA/CS/GL nanofiber membrane has potential application value in medical trauma dressings.&nbsp;<br>

Bone defects requiring grafts to promote healing are frequently occurring and costly problems in health care. Chitosan, a biodegradable, naturally occurring polymer, has drawn considerable attention in recent years as scaffolding material in tissue engineering and regenerative medicine. Chitosan is especially attractive as a bone scaffold material because it supports the attachment and proliferation of osteoblast cells as well as formation of mineralized bone matrix. In this review, we discuss the fundamentals of bone tissue engineering and the unique properties of chitosan as a scaffolding material to treat bone defects for hard tissue regeneration. We present the common methods for fabrication and characterization of chitosan scaffolds, and discuss the influence of material preparation and addition of polymeric or ceramic components or biomolecules on chitosan scaffold properties such as mechanical strength, structural integrity, and functional bone regeneration. Finally, we highlight recent advances in development of chitosan-based scaffolds with enhanced bone regeneration capability.

Relations were studied between skin temperature of the back as well as temperature and humidity inside clothing, and subjective estimates of thermal, humidity, and comfort sensations in 5 subjects wearing cross-country ski dress. The 2-h wear trials were performed in a climatic chamber at −2°C and simulated the actual circumstances under which such a dress is worn by alternating periods of intensive walking (20 min) on a treadmill with periods of resting (5–10 min). Each subject participated in 4 trials wearing alternately one of the 4 experimental, double-layer vests (double-cotton, cotton-polypropylene with cotton layer next to skin, same combination with polypropylene layer next to skin, double-polypropylene).

基于先进的静电纺丝技术,旨在制备出高质量的聚偏氟乙烯(PVDF)纳米纤维膜,并系统地探究了影响纺丝工艺的关键因素。通过调控PVDF质量分数(12%)、溶剂体系中N,N-二甲基甲酰胺(DMF)与丙酮的质量比例(5∶5)、供液流速(1mL/h)、外加电场强度(18kV),以及针尖至接收装置(转辊)的间距(15cm),以确立并验证最佳的纺丝工艺参数组合。结果表明:在上述最优工艺条件下制备的PVDF纳米纤维膜,展现出了优异的微观结构形态,且其β晶相含量高达83.1%,这一发现不仅验证了工艺参数优化的有效性,也为后续纳米材料在特定领域(如过滤、传感、能量存储等)的应用提供了坚实的基础和广阔的前景。

The objective of this study was to prepare high-quality polyvinylidene fluoride (PVDF) nanofibrous membranes using advanced electrostatic spinning technology.The key factors affecting the spinning process were also systematically investigated.The mass concentration of PVDF was set at 12wt%,the mass ratio of <i>N,N</i>-dimethylformamide (DMF) to acetone in the solvent system was fixed at 5∶5,the flow rate of the supply liquid was maintained at 1mL/h,the strength of the applied electric field was set at 18kV,and the distance from the tip of the needle to the receiving device (rotating rollers) was set at 15cm.These parameters were regulated to establish and validate the optimal combination of spinning process parameters.The experimental results demonstrated that the PVDF nanofibrous membranes prepared under the aforementioned optimal process conditions exhibited an excellent microstructural morphology,with a β-crystalline phase content of up to 83.1%.This finding not only validated the effectiveness of the process parameter optimisation but also provided a solid foundation and broad prospects for the subsequent application of the nanomaterials in specific fields,such as filtration,sensing,and energy storage.

Biodegradable nanofibers produced by electrospinning represent a new class of promising scaffolds to support nerve regeneration. We begin with a brief discussion on the electrospinning of nanofibers and methods for controlling the structure, porosity, and alignment of the electrospun nanofibers. The methods include control of the nanoscale morphology and microscale alignment of the nanofibers, as well as the fabrication of macroscale, three-dimensional tubular structures. We then highlight recent studies that utilize electrospun nanofibers to manipulate biological processes relevant to nervous tissue regeneration, including stem cell differentiation, guidance of neurite extension, and peripheral nerve injury treatments. The main objective of this feature article is to provide valuable insights into methods for investigating the mechanisms of neurite growth on novel nanofibrous scaffolds and optimization of the nanofiber scaffolds and conduits for repairing peripheral nerve injuries.

The fibrocartilaginous menisci are load-bearing tissues vital to the normal functioning of the knee. Removal of damaged regions of the meniscus subsequent to injury impairs knee function and predisposes patients to osteoarthritis. In this study, we employed biodegradable nanofibrous scaffolds for the tissue engineering of the meniscus. Non-aligned (NA) or fiber-aligned (AL) nanofibrous scaffolds were seeded with meniscal fibrochondrocytes (MFCs) or mesenchymal stem cells (MSCs) to test the hypothesis that fiber-alignment would augment matrix content and organization, resulting in improved mechanical properties. Additionally, we proposed that MSCs could serve as an alternative to MFCs. With time in culture, MSC- and MFC-seeded NA and AL constructs increased in cellularity and extracellular matrix (ECM) content. Counter our initial hypothesis, NA and AL constructs contained comparable amounts of ECM, although a significantly larger increase in mechanical properties was observed for AL compared to NA constructs seeded with either cell type. Cell-seeded NA constructs increased in modulus by approximately 1MPa over 10 weeks while cell-seeded AL construct increased by >7MPa. Additionally, MSC-constructs yielded greater amounts of ECM and demonstrated comparable increases in mechanical properties, thereby confirming the utility of MSCs for meniscus tissue engineering. These results demonstrate that cell-seeded fiber-aligned nanofibrous scaffolds may serve as an instructive micro-pattern for directed tissue growth, reconstituting both the form and function of the native tissue.

Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.

Mesenchymal stem cells (MSCs), the major stem cells for cell therapy, have been used in the clinic for approximately 10 years. From animal models to clinical trials, MSCs have afforded promise in the treatment of numerous diseases, mainly tissue injury and immune disorders. In this review, we summarize the recent opinions on methods, timing and cell sources for MSC administration in clinical applications, and provide an overview of mechanisms that are significant in MSC-mediated therapies. Although MSCs for cell therapy have been shown to be safe and effective, there are still challenges that need to be tackled before their wide application in the clinic.

Conductive hydrogels (CHs) combine the biomimetic properties of hydrogels with the physiological and electrochemical properties of conductive materials, and have attracted extensive attention in the past few years. In addition, CHs have high conductivity and electrochemical redox properties and can be used to detect electrical signals generated in biological systems and conduct electrical stimulation to regulate the activities and functions of cells including cell migration, cell proliferation, and cell differentiation. These properties give CHs unique advantages in tissue repair. However, the current review of CHs is mostly focused on their applications as biosensors. Therefore, this article reviewed the new progress of CHs in tissue repair including nerve tissue regeneration, muscle tissue regeneration, skin tissue regeneration and bone tissue regeneration in the past five years. We first introduced the design and synthesis of different types of CHs such as carbon-based CHs, conductive polymer-based CHs, metal-based CHs, ionic CHs, and composite CHs, and the types and mechanisms of tissue repair promoted by CHs including anti-bacterial, antioxidant and anti-inflammatory properties, stimulus response and intelligent delivery, real-time monitoring, and promoted cell proliferation and tissue repair related pathway activation, which provides a useful reference for further preparation of bio-safer and more efficient CHs used in tissue regeneration.This journal is © The Royal Society of Chemistry.