Gang Xu

Diabetes mellitus, a metabolic disorder characterized by chronic inflammation and hyperglycemia, is projected to affect 589 million adults (aged 20– 79) globally in 2024, soaring to 853 million by 2050. Diabetic wounds, particularly diabetic foot ulcers (DFUs), afflict over 15 million patients annually. These wounds are notoriously refractory to healing, prone to infection, and associated with high rates of amputation and mortality, posing a severe burden on healthcare systems worldwide. The impaired healing trajectory stems from a complex pathophysiology involving neuropathy, angiopathy, and immune dysfunction in the hyperglycemic milieu, which renders conventional passive dressings inadequate. Although extensive research has been devoted to developing advanced dressings loaded with various bioactive agents, the majority of these efforts remain confined to optimizing single-material platforms or isolated functional enhancements, lacking a comprehensive and globally integrated design theory that addresses the multi-stage, multi-target pathological features of diabetic wound healing. To address this gap, this review proposes and systematically articulates a tripartite design paradigm—namely, "pathology-timing matching, multimodal bioactivity synergy, and smart microenvironment responsiveness”—which serves as the overarching analytical framework throughout the manuscript. Within this framework, we comprehensively survey current diverse material platforms, such as hydrogels, polymer-based composites, and nanocomposites, alongside a broad spectrum of bioactive factors, including active compounds derived from traditional Chinese medicine (TCM) and placental-derived biologics. Importantly, we depart from conventional encyclopedic enumeration by shifting our focus to elucidate how distinct material–biofactor combinations exert spatiotemporal synergistic effects across specific healing phases, such as inflammation regulation, angiogenesis, and infection control. Furthermore, we delve into the dynamic responsiveness of smart dressings to wound microenvironmental cues (eg, pH, temperature, oxygen tension, and specific infectious biomarkers) Prospectively, we propose the integration of real-time data feedback from smart dressings with the construction of wound "digital twins”, thereby charting a new avenue toward precision and personalized therapeutics Finally, we distill the core challenges associated with the deep convergence of multimodal synergistic strategies and intelligent responsive systems and outline future research directions for the development of next-generation personalized therapeutic solutions for diabetic wound management.

The escalating global burden of an aging population and the rising incidence of secondary traumatic injuries have precipitated a mounting worldwide demand for bone grafts. However, autologous bone transplantation-the prevailing clinical "gold standard"-remains insufficient to meet this growing clinical need. Notably, rapid advancements in bone tissue engineering (BTE) have yielded diverse bone graft substitutes designed to recapitulate the three essential characteristics of bone tissue: osteoconductivity, osteoinductivity, and osteogenic potential. Within this domain, core scaffolds functioning as carriers for bioactive agents represent a highly promising strategy for treating bone defects. This review focuses on the design and fabrication of optimal xenogeneic bone scaffolds. It systematically examines commonly loaded bioactive components, including bone morphogenetic proteins (BMPs), platelet-rich plasma (PRP), natural products, active ingredients derived from traditional Chinese medicine ingredients (TCMs), and exosomes. The advantages and limitations inherent to these agents are critically analyzed. Furthermore, the review addresses current challenges and explores future research directions in bone scaffold engineering. By advancing multimodal strategies for modulating the delivery of bioactive agents, we aim to provide more effective therapeutic solutions for patients with critical bone defects.

The clinical repair of bone defects is hindered by limitations in donor material and complications arising from autologous bone grafting. Consequently, the development of efficient bone regeneration materials is of great clinical importance. The present study investigated a three-dimensional microporous demineralized bone matrix (DBM) combined with bone marrow mesenchymal stem cells (BMSCs) to enhance the outcomes of bone defect repair. The DBM has been developed to enhance the collagen preparation process, with the aim of retaining the collagen fiber network of the natural bone matrix and forming a three-dimensional microporous structure with good mechanical property. In vitro experiments demonstrated that the biocompatibility of DBM was superior to that of traditional cancellous and cortical bone materials, and they promoted cell adhesion, proliferation, and osteogenic differentiation as well as osteogenesis-related genes. In vivo experimentation was conducted to verify the efficacy of the treatment on a critical-sized cranial bone defect in nude mice. Micro-CT and histological analysis showed more formation of bone at 4 weeks and 8 weeks postsurgery. The DBM with optimized pore structure, degradation rate, and bioactivity enhanced the efficiency of bone defect repair by synergizing the osteogenic activity of BMSCs. The DBM with a porous and cross-linked structure could provide BMSCs with more internal surface area for attachment space to promote cell adhesion and growth and create advantages for the bone formation. Moreover, the DBM contains multifarious osteoinductive growth factors such as transforming growth factor-β (TGF-β), fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs) and insulin growth factors (IGFs), which can enhance osteogenic differentiation of BMSCs. This study may provide an innovative strategy for bone regeneration and bone defect repair.

Bones can sense bioelectricity. The process of bone remodeling and repair needs complex physiological signals like bioelectric, biochemical, and biomechanical factors, which work together to promote bone recovery. The formation, healing, and regeneration of natural bones are intricately linked to the influence of electrical signals. Piezoelectric materials have piezoelectric properties similar to bones, making them suitable for bone like repair. This study systematically summarizes the role of piezoelectric materials in bone remodeling and repair, as well as their related preparation techniques. Subsequently, the piezoelectric mechanism of bones is explored in depth, including the study of bone composition, analysis of piezoelectric and osteogenic mechanisms, and research progress on piezoelectric stimulation guided bone regeneration and repair. Through these analyses, the principle of how piezoelectric materials interact with bones to promote bone repair and remodeling has been further understood. Finally, the article analyzes the mechanism of piezoelectric materials on bone remodeling and repair, revealing how piezoelectric stimulation promotes bone regeneration and repair. These findings offer theoretical foundation and practical guidance for the further application of piezoelectric materials in orthopedics.

Adolescent lumbar disc herniation (ALDH) is a type of disease with a much lower incidence than adult lumbar disc herniation (LDH), which has a trend of increasing year by year. If the diagnosis is not timely or the treatment is not appropriate, it will have a serious impact on the adolescent’s psychology. The etiology of ALDH remains unclear, and it is thought that trauma, genetic, immunity, developmental abnormalities, and biomechanical abnormalities contribute to the onset and accelerate ALDH’s progression. The diagnosis of ALDH is similar to that of adults, but it has its characteristics, such as a positive straight leg raising (SLR) test in nearly 90% of patients, and posterior apophyseal ring fracture (PARF) is considered a characteristic imaging finding of ALDH. First-line treatment for ALDH remains conservative, although it is less effective than in adults. With the development of regenerative medicine, more and more treatment methods for small traumas have been applied to ALDH and achieved satisfactory treatment results. In the case of the above treatment, the effect is not satisfactory, surgery has become the last choice, different from the earliest use of open discectomy combined with fusion surgery, now more and more surgeries tend to use spinal endoscopic operation to solve, especially patients combined with some high-risk factors, and achieved satisfactory results. With the deepening of ALDH research, the etiology and mechanism of ALDH may be more fully understood. At the same time, with the development of Artificial intelligence (AI) technology, it is believed that in the near future, AI can provide references in the timing of conservative treatment for ALDH, the selection of surgical modalities, and the prediction of postoperative complications.

Bone tissue, the second most transplanted tissue after blood, is utilized in over 2.2 million bone grafts annually to address various bone-related conditions including fractures, tumors, bone infections, scoliosis, congenital defects, osteoporosis, osteoarthritis, and osteogenesis imperfecta. According to incomplete statistics, $4.3 billion was spent on bone graft materials in 2015 alone, with projections suggesting this figure may reach $66 billion by 2026. The limited availability of autogenous bone graft considered the gold standard due to their three critical biological properties: osteoconduction, osteoinduction, and osteogenesis-alongside the increasing global aging population, may be contributing to this rising expenditure. Furthermore, advancements in biomaterials and engineering technologies have created opportunities for the exploration of new bone graft substitutes. In this review, we will examine the fundamental structure of natural bone and the characteristics of ideal bone graft, highlighting common bone graft materials currently available, such as true bone ceramics, decalcified bone matrix, freeze-dried bone and demineralized freeze-dried bone, bioactive glasses, bone marrow aspirate concentrate, polymer nanocomposites, which have different characteristics in osteogenic, osteoconductivity, osteoinductivity, biocompatibility, mechanical properties, and resorption. How to utilize its advantages to maximize the osteogenic effect will be the focus of this review, and some of the current challenges in the field of bone grafting will be identified, outlining potential directions for future development. In conclusion, the choice of bone graft is critical to bone repair and regeneration, and a comprehensive understanding of the advantages and disadvantages of bone graft materials can improve the effectiveness of related surgical interventions.

Freeze-dried bone (FDB) scaffolds present several advantages, including mechanical strength, osteoconductive properties, and abundant availability. This study aimed to investigate the osteogenic effects and underlying mechanisms of bovine FDB combined with Rehmannia glutinosa Libosch polysaccharide (RGP) on bone defects and fractures in rats. The characteristics of the scaffolds were analyzed through observational studies, scanning electron microscopy imaging, mechanical strength testing, cytotoxicity assessments, and in vitro RGP release. Subsequently, femoral condyle and radial defect models mimicking bone defect and fracture were used to evaluate the scaffolds' repair capabilities for cortical and cancellous bone defects. Results obtained at the eighth week showed that FDB&RGP combination outperformed FDB alone in various parameters, indicating superior repair potential for both bone types, as well as for bone defects and fractures. The combination scaffold exhibited enhanced osteoinductive properties, rendering it more suitable for bone defect repair. The osteogenic mechanisms of FDB&RGP were investigated using alkaline phosphatase (ALP) and Alizarin Red S staining, as well as assessments of ALP, OCN, and COL1 activities, and the activation of the BMP-9/GSK3β signaling pathway. The results indicate that FDB&RGP enhances osteo-differentiation, with the BMP-9/GSK3β pathway potentially serving a pivotal role. This study establishes a foundation for the future clinical application of xenograft FDB&RGP.

Serum urate (SU) levels are significantly elevated in conditions such as gout, type 2 diabetes (T2D), obesity, and other metabolic syndromes. Recently, due to the high prevalence of hyperuricemia (HUA), numerous clinical connections between SU and musculoskeletal disorders like sarcopenia, osteoarthritis (OA), rheumatoid arthritis (RA), intervertebral disc degeneration (IDD), and osteoporosis (OP) have been identified. This review discusses the mechanisms linking SU to musculoskeletal disorders, as well as the clinical associations of SU with conditions such as sarcopenia, T2D with sarcopenia, McArdle disease, heart failure, gout, OA, IDD, OP and exercise-induced acute kidney injury (EIAKI), offering valuable insights for improved prevention and treatment strategies. Mechanisms linking SU to musculoskeletal disorders include oxidative stress, MSU (monosodium urate) crystal deposition, inflammation, and other factors. In adults, both age and SU levels should be considered for preventing sarcopenia, while gender and SU may directly impact muscle mass in children and adolescents. HUA and gout may be risk factors for OA progression, although some reports suggest otherwise. A U-shaped relationship between SU and IDD has been reported, particularly in Chinese men, indicating lower or higher SU level may be risk factors for IDD. Maintaining SU levels within a certain range may help prevent OP and fractures. Future research, including epidemiological studies and new pathogenesis findings, will further clarify the relationship between musculoskeletal diseases and SU.

An acellular bovine bone matrix modified to release Magnesium ions (Mg²⁺) (ABBM-Mg) was prepared and evaluated for its potential in osteogenesis and mandibular defect repair. Mg²⁺ was incorporated into ABBM using an ion exchange method. The microstructure and mechanical properties of both ABBM and ABBM-Mg were analyzed using SEM and a biomechanical testing machine. Cytocompatibility, cell adhesion, and osteogenic differentiation were assessed using various methods including CCK-8, Live/Dead staining, SEM, ALP staining, and qPCR analysis in MC3T3-E1 cells. Additionally, a mandibular defect model in rats was established. The bone defect repair outcomes were evaluated using Micro-CT, histological HE staining, and Masson staining. The study showed that mineralization containing magnesium was redeposited on the surface of the three-dimensional porous ABBM, and the ABBM-Mg scaffold promoted cell proliferation and osteogenic differentiation compared to the ABBM scaffold. In the rat mandibular defect model, the ABBM-Mg scaffold demonstrated superior bone repair ability. This study successfully incorporated Mg²⁺ into ABBM without significantly affecting its microstructure and compressive strength. Furthermore, ABBM-Mg showed sustained release of Mg²⁺ which enhanced cell proliferation, adhesion, and osteogenic differentiation in vitro, and promoted mandibular defect healing in rats. This research opens up new possibilities for the clinical application of functionalized acellular bone matrix. Graphical Abstract

Spinal cord injury (SCI) is a severe traumatic spinal condition with a poor prognosis. In this study, a scaffold called linearly ordered collagen aggregates (LOCAS) was created and loaded with induced pluripotent stem cells (iPSCs)-derived neural stem cells (NSCs) from human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) to treat SCI in a rat model. The rats underwent a complete transection SCI resulting in a 3-mm break at either the T9 or T10 level of the spinal cord. Scanning electron microscope analysis revealed a uniform pore structure on the coronal plane of the scaffold. The LOCAS had a porosity of 88.52% and a water absorption of 1161.67%. Its compressive modulus and stress were measured at 4.1 MPa and 205 kPa, respectively, with a degradation time of 10 weeks. After 12 weeks, rats in the LOCAS-iPSCs-NSCs group exhibited significantly higher BBB scores (8.6) compared to the LOCAS-iPSCs-NSCs group (5.6) and the Model group (4.2). The CatWalk analysis showed improved motion trajectory, regularity index (RI), and swing speed in the LOCAS-iPSCs-NSCs group compared to the other groups. Motor evoked potentials latency was lower and amplitude was higher in the LOCAS-iPSCs-NSCs group, indicating better neural function recovery. Histological analysis demonstrated enhanced neuronal differentiation of NSCs and nerve fiber regeneration promoted by LOCAS-iPSCs-NSCs, leading to improved motor function recovery in rats. The LOCAS scaffold facilitated ordered neurofilament extension and guided nerve regeneration. The combination of LOCAS and iPSCs-NSCs demonstrated a positive therapeutic impact on motor function recovery and tissue repair in rats with SCI. This development offers a more resilient bionic microenvironment and presents novel possibilities for clinical SCI repair.