Thetreatment of infected wounds is currently a major challenge in clinical medicine, and enhancing antimicrobial and angiogenic capacity is one of the most common strategies. However, the current treatment makes it difficult to balance the antimicrobial effect in the early stage and the angiogenic effect in the later stages of wound healing, leading to an increased rate of poor prognosis. Here, we present a nanoconductive hydrogel EF@S-HGM, consisting of HGM with ECGS, FMLP, and SWCNT. The host-guest supramolecular macromolecule (HGM) hydrogel is biocompatible and can be injected in situ in the wound. The endothelial cell growth factor (ECGS) accelerates vascular remodeling and repairs wounds by promoting the proliferation of endothelial cells. N-Formyl-Met-Leu-Phe (FMLP) recruits neutrophils and increases the antimicrobial capacity. Single-walled carbon nanotubes (SWCNT) make the hydrogel conductive, enabling the hydrogel to utilize the endogenous electric field in the wound to recruit multiple kinds of cells. In addition, we found that the EF@S-HGM hydrogel activates the glucocorticoid receptor senescence pathway and promotes the formation of NET, which enhances the antimicrobial effect. As tissue-engineered skin, the conductive hydrogel EF@S-HGM is a promising material for regenerative medicine that may provide a potential option for the treatment and care of infected wounds and significantly improve patient outcomes and prognosis.

Photoacoustic imaging (PAI) is a promising emerging technology in biomedical imaging, particularly in wound healing. This review summarizes the applications of PAI in the detection and management of complex wounds, emphasizing its advantages in providing high-contrast, high-resolution deep tissue imaging. PAI integrates optical imaging's high contrast with ultrasound's deep penetration, facilitating the monitoring of vital physiological parameters like blood flow, oxygen saturation, and tissue regeneration in wounds. The review details the applications of PAI in monitoring wound pH, nerve repair, drug absorption, burn imaging, and infection-related wound assessment. It also explores the role of novel materials like carbon-based materials, nanorobots, and inorganic nanoparticles in enhancing PAI capabilities. Despite the technical challenges and limitations in clinical applications, PAI holds tremendous potential for wound healing monitoring. The review concludes by addressing the challenges and solutions for PAI, along with future development directions, to facilitate the transition of PAI technologies from experimental stages to clinical application.

Imbalanced inflammatory response and impaired angiogenesis are significant factors contributing to the non- healing of diabetic wounds. The susceptibility to bacterial infection further complicates the management of diabetic wounds. Here, an innovative "Tri-Act" bilayer hydrogel dressing (AlgHA-MFE/sHA-sEVsmiR) has been developed, which integrates visual monitoring of wound infection, immune regulation, and angiogenesis promotion, aiming to address the complex challenges posed by diabetic infected wounds. Utilizing the pH- responsive color-changing properties of anthocyanin-rich mulberry fruit extract (MFE), the upper layer of the hydrogel is endowed with the capability to visually monitor infections. Additionally, miR-210-3p-engineered small extracellular vesicles (sEVsmiR) are constructed and encapsulated in the lower layer hydrogel composed of Schiff base crosslinked hyaluronic acid (sHA). Regarding the therapeutic aspect, sEVsmiR is released from the hydrogel in a pH-responsive manner, thereby improving its utilization. In diabetic infected wounds, AlgHA-MFE/ sHA-sEVsmiR hydrogel exhibits effective hemostasis and antibacterial effects, while alleviating oxidative stress and endoplasmic reticulum stress in the wound area. By enhancing macrophage M2 polarization and angiogenesis, the hydrogel achieves therapeutic efficacy superior to traditional treatments. These results highlight the potential of this "Tri-Act" hydrogel to improve diabetic wound management, providing new insights into the development of novel wound dressings.

Fracture repair involves a highly coordinated physiological process comprising inflammatory, repair, and remodeling phases. Modulating the immune microenvironment across these stages presents a promising therapeutic avenue, particularly through the regulation of neutrophils, key innate immune cells that play a dual role: remove tissue debris and bacteria while impairing subsequent tissue repair. Although current approaches aim to modulate immune balance, the precise mechanisms governing neutrophil activity and their targeted modulation remain underexplored. Herein, we present an injectable hydrogel (HSM/TC-cmEVs) engineered from a hydrazide-grafted hyaluronic acid (HA-ADH), oxidized sodium alginate (OSA), and magnesium ion (Mg2+) composite. The hydrogel provides a sustained release of tetracycline-modified M2 macrophage-derived extracellular vesicles (TC-cmEVs) that express CXCL-12, and forms a “trap” at the fracture site to selectively recruit and neutralize neutrophils. This mechanism rebalances the immune microenvironment, mitigating neutrophil-mediated damage while concurrently preventing infection via the antimicrobial properties conferred by tetracycline. Additionally, Mg2+ within the hydrogel enhances osteogenesis and angiogenesis while inhibiting osteoclast formation, collectively accelerating bone regeneration. These multifunctional properties indicate that the HSM/TC-cmEVs hydrogel represents a compelling strategy for enhancing fracture repair through targeted immune modulation and tissue regeneration.

In infected wounds, adipocytes play a crucial role in resisting infection. Studies have demonstrated that a lack of adipocytes can reduce the recruitment of macrophages. When wounds are infected, dermal fibroblasts (dFBs) differentiate into adipocytes and produce antimicrobial peptides (AMPs) to combat bacteria. However, in obesity mice, mature adipocytes hinder the adipogenic differentiation of dFBs and the production of AMPs. It is unclear whether promoting lipolysis can restore the function of AMPs secretion. Nickel ion (Ni2+) is known for promoting vascular regeneration and has been widely used in tissue regeneration. Therefore, the ROS-responsive ferulic acid (FA)@Ni@HA hydrogel was developed to promote infected wound healing. FA released from the hydrogel can promote the lipolysis of adipocytes to alleviate the inhibition of mature adipocytes on AMPs secretion from dFBs and enhance macrophage recruitment. Additionally, the loaded Ni2+ can stimulate local blood vessel formation, working in conjunction with FA to promote the healing of infected wounds. The results suggest that the use of FA@Ni@HA hydrogel expedites the repair of infected wounds, offering a promising strategy for wound healing.

Diabetes-associated chronic skin wounds present a formidable challenge due to inadequate angiogenesis and nerve regeneration during the healing process. In the present study, we introduce a groundbreaking approach in the form of a novel cocktail therapy utilizing a multifunctional supramolecular hydrogel. Formulated through the photo-crosslinking of gelatinized aromatic residues and β-cyclodextrin (β-CD), this injectable hydrogel fosters weak host-guest interactions, offering a promising solution. The therapeutic efficacy of the hydrogel is realized through its integration with adipose-derived stem cells (ADSCs) and lipid nanoparticles encapsulating ginsenoside RG1 and Stromal cell-derived factor-1 (SDF-1). This strategic combination directs ADSCs to the injury site, guiding them toward neurogenic specialization while establishing an advantageous immunomodulatory environment through macrophage reprogramming. The synergistic effects of the newly differentiated nerve cells and the regenerative cytokines secreted by ADSCs contribute significantly to enhanced angiogenesis, ultimately expediting the diabetic wound healing process. To summarize, this innovative hydrogel-based therapeutic system represents a novel perspective for the management of diabetic wounds by concurrently targeting immune response, angiogenesis, and nerve regeneration—a pivotal advancement in the quest for effective solutions in diabetic wound care.

This article has been corrected: The authors found an error in Figure 5G, which depicts transwell migration assays assessing the effects of miR-15a-3p inhibition on HUVEC cells. The central panel, illustrating migration of HUVECs treated with exosomes derived from DFU individuals (Dia-Exos), was replaced with the appropriate image from the original set of experiments. This inadvertent error does not in any way compromise the validity or integrity of the study's findings. The authors take full responsibility for this oversight and sincerely apologize for any inconvenience caused.

The healing of diabetic skin wounds is a complex process significantly affected by the hyperglycemic environment. In this context, glucose oxidase (GOx), by catalyzing glucose to produce gluconic acid and hydrogen peroxide, not only modulates the hyperglycemic microenvironment but also possesses antibacterial and oxygen-supplying functions, thereby demonstrating immense potential in the treatment of diabetic wounds. Despite the growing interest in GOx-based therapeutic strategies in recent years, a systematic summary and review of these efforts have been lacking. To address this gap, this review article outlines the advancements in the application of GOx and GOx-like nanozymes in the treatment of diabetic wounds, including reaction mechanisms, the selection of carrier materials, and synergistic therapeutic strategies such as multi-enzyme combinations, microneedle structures, and gas therapy. Finally, the article looks forward to the application prospects of GOx in aiding the healing of diabetic wounds and the challenges faced in translating these innovations to clinical practice. We sincerely hope that this review can provide readers with a comprehensive understanding of GOx-based diabetic treatment strategies, facilitate the rigorous construction of more robust multifunctional therapeutic systems, and ultimately benefit patients with diabetic wounds.

PurposeThis study aims to depict the scientific advancements in immunotherapy for glioma by analyzing the top 100 most frequently cited articles over the past 20 years.MethodsThe top 100 most influential papers in immunotherapy for glioma were identified from the Web of Science Core Collection. Citations, countries/regions, institutions, journals, authorships, keywords, and references were extracted and analyzed by CiteSpace, VOSviewer, R software, and an online bibliometric platform.ResultsThe United States possessed a robust global presence, leading in terms of publications and maintaining strong collaborative ties with numerous countries. The institution that made the greatest contributions was Duke University, with 16 papers. Heimberger AB, Sampson JH, and Reardon DA secured the top three positions with 15, 12, and 11 papers, respectively. “Macrophage ontogeny,” “microglia,” “polarization,” “mass cytometry,” “tumor mutation burden,” “sensitivity,” “msh6,” “pd-1 blockade,” and “dna repair” were the recent hot keywords. “Microglia” and “polarization” as the emerging research directions should be given more consideration.ConclusionsThis is the first bibliometric analysis to identify the top 100 papers on immunotherapy for glioma. “Microglia” and “polarization” will be hot spots for future research. The clinical efficacy of glioma immunotherapy is not yet satisfactory, and there is an urgent need to search for more tumor specific antigens and targets that can assist in early diagnosis, precise treatment, prognosis, and recurrence prediction of glioma.

Diabetic wound (DW) therapy is currently a big challenge in medicine and strategies to enhance neurogenesis and angiogenesis have appeared to be a promising direction. However, the current treatments have failed to coordinate neurogenesis and angiogenesis simultaneously, leading to an increased disability rate caused by DWs. Herein, a whole-course-repair system is introduced by a hydrogel to concurrently achieve a mutually supportive cycle of neurogenesis-angiogenesis under a favorable immune-microenvironment. This hydrogel can first be one-step packaged in a syringe for later in situ local injections to cover wounds long-termly for accelerated wound healing via the synergistic effect of magnesium ions (Mg2+) and engineered small extracellular vesicles (sEVs). The self-healing and bio-adhesive properties of the hydrogel make it an ideal physical barrier for DWs. At the inflammation stage, the formulation can recruit bone marrow-derived mesenchymal stem cells to the wound sites and stimulate them toward neurogenic differentiation, while providing a favorable immune microenvironment via macrophage reprogramming. At the proliferation stage of wound repair, robust angiogenesis occurs by the synergistic effect of the newly differentiated neural cells and the released Mg2+, allowing a regenerative neurogenesis-angiogenesis cycle to take place at the wound site. This whole-course-repair system provides a novel platform for combined DW therapy.

Fracture combined with traumatic brain injury (TBI) is one of the most common and serious types of compound trauma in the clinic and is characterized by dysfunction of cellular communication in injured organs. Our prior studies found that TBI was capable of enhancing fracture healing in a paracrine manner. Exosomes (Exos), as small extracellular vesicles, are important paracrine vehicles for noncell therapy. However, whether circulating Exos derived from TBI patients (TBI-Exos) regulate the prohealing effects of fractures remains unclear. Thus, the present study aimed to explore the biological effects of TBI-Exos on fracture healing and reveal the potential molecular mechanism. TBI-Exos were isolated by ultracentrifugation, and the enriched miR-21-5 p was identified by qRT‒PCR analysis. The beneficial effects of TBI-Exos on osteoblastic differentiation and bone remodeling were determined by a series of in vitro assays. Bioinformatics analyses were conducted to identify the potential downstream mechanisms of the regulatory effect of TBI-Exos on osteoblasts. Furthermore, the role of the potential signaling pathway of TBI-Exos in mediating the osteoblastic activity of osteoblasts was assessed. Subsequently, a murine fracture model was established, and the effect of TBI-Exos on bone modeling was demonstrated in vivo. TBI-Exos can be internalized by osteoblasts, and in vitro, suppression of SMAD7 promoted osteogenic differentiation, whereas knockdown of miR-21-5 p in TBI-Exos strongly inhibited this bone-beneficial effect. Similarly, our results confirmed that preinjection of TBI-Exos led to enhanced bone formation, whereas knockdown of exosomal miR-21-5 p substantially impaired this bone-beneficial effect in vivo.

As the National Health Commission changes the management of novel corona virus infection, the situation and preventive policies for controlling the epidemic have also entered a new stage in China. Perioperative care strategies for orthopedic trauma such as designated isolation and nucleic acid test screening have also been adjusted in the new stage. Based on the perioperative work experiences in the new stage of epidemic from the frontline anti-epidemic staff of orthopedics in domestic hospitals and combined with the literature and relevant evidence-based medical data in perioperative care of orthopedic trauma patients under the current anti-epidemic policies at home and abroad, Chinese Orthopedic Association and Chinese Society of Traumatology organized relevant experts to formulate the Guideline for clinical perioperative care of orthopedic trauma patients in the new stage of novel corona virus infection ( version 2023). The guideline summarized 16 recommendations from the aspects of preoperative diagnosis and treatment, infection prevention, emergency operation and postoperative management to systematically standardize the perioperative clinical pathways, diagnosis and treatment processes of orthopedic trauma in the new stage of novel corona virus infection, so as to provide a guidance and reference for hospitals at all levels to carry out relevant work in current epidemic control policies.

The treatment of diabetic wounds remains a major challenge in clinical practice, with chronic wounds characterized by multiple drug-resistant bacterial infections, angiopathy, and oxidative damage to the microenvironment. Herein, a novel in situ injectable HA@MnO2 /FGF-2/Exos hydrogel is introduced for improving diabetic wound healing. Through a simple local injection, this hydrogel is able to form a protective barrier covering the wound, providing rapid hemostasis and long-term antibacterial protection. The MnO2 /ε-PL nanosheet is able to catalyze the excess H2 O2 produced in the wound, converting it to O2 , thus not only eliminating the harmful effects of H2 O2 but also providing O2 for wound healing. Moreover, the release of M2-derived Exosomes (M2 Exos) and FGF-2 growth factor stimulates angiogenesis and epithelization, respectively. These in vivo and in vitro results demonstrate accelerated healing of diabetic wounds with the use of the HA@MnO2 /FGF-2/Exos hydrogel, presenting a viable strategy for chronic diabetic wound repair.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Although the immune system is well recognized as a key player in fracture repair, the exact mechanisms, particularly the role of regulatory T-cells (Tregs), have not yet been established. Our increased understanding of the Tregs and exosomes involved in organ repair creates opportunity of application of Tregs derived Exosomes (TregD-Exos) in the modulation of fracture repair. In the present study, we report that TregD-Exos containing miR-142-3p can be shuttled into bone mesenchymal stem cells (BMSCs) and Human umbilical vein endothelial cells (HUVECs) promoting osteogenesis and angiogenesis. Overexpression of miR-142-3p remarkedly promoted BMSC osteoblastic differentiation, and enhanced HUVEC function, including proliferation, migration and angiogenesis. Furthermore, TGFBR1/SMAD2 was shown to be involved in the TregD-Exos’ promotive effect on bone healing. Moreover, both TregD-Exos and miR-142-3p administration restored bone repair in vivo. Taken together, our results indicate that TregD-Exos containing miR-142-3p can be transferred to BMSCs and HUVECs with robust effects on osteogenesis and angiogenesis. These findings shed a new light for the use of Tregs in facilitating bone repair, suggesting that both TregD-Exos and miR-142-3p are promising effective therapeutic agents for bone remodeling.

MicroRNAs (miRNAs) broadly regulate normal biological functions of bone and the progression of fracture healing and osteoporosis. Recently, it has been reported that miR-1224-5p in fracture plasma is a potential therapy for osteogenesis. To investigate the roles of miR-1224-5p and the Rap1 signaling pathway in fracture healing and osteoporosis development and progression, we used BMMs, BMSCs, and skull osteoblast precursor cells for in vitro osteogenesis and osteoclastogenesis studies. Osteoblastogenesis and osteoclastogenesis were detected by ALP, ARS, and TRAP staining and bone slice resorption pit assays. The miR-1224-5p target gene was assessed by siRNA-mediated target gene knockdown and luciferase reporter assays. To explore the Rap1 pathway, we performed high-throughput sequencing, western blotting, RT-PCR, chromatin immunoprecipitation assays and immunohistochemical staining. In vivo, bone healing was judged by the cortical femoral defect, cranial bone defect and femoral fracture models. Progression of osteoporosis was evaluated by an ovariectomy model and an aged osteoporosis model. We discovered that the expression of miR-1224-5p was positively correlated with fracture healing progression. Moreover, in vitro, overexpression of miR-1224-5p slowed Rankl-induced osteoclast differentiation and promoted osteoblast differentiation via the Rap1-signaling pathway by targeting ADCY2. In addition, in vivo overexpression of miR-1224-5p significantly promoted fracture healing and ameliorated the progression of osteoporosis caused by estrogen deficiency or aging. Furthermore, knockdown of miRNA-1224-5p inhibited bone regeneration in mice and accelerated the progression of osteoporosis in elderly mice. Taken together, these results identify miR-1224-5p as a key bone osteogenic regulator, which may be a potential therapeutic target for osteoporosis and fracture nonunion.

The ubiquitination-proteasome system (UPS) is crucial in regulating a variety of cellular processes including proliferation, differentiation, and survival. Ubiquitin protein ligase E3 is the most critical molecule in the UPS system. Dysregulation of the UPS system is associated with many conditions. Over the past few decades, there have been an increasing number of studies focusing on the UPS system and how it affects bone metabolism. Multiple E3 ubiquitin ligases have been found to mediate osteogenesis or osteolysis through a variety of pathways. In this review, we describe the mechanisms of UPS, especially E3 ubiquitin ligases on bone metabolism. To date, many E3 ubiquitin ligases have been found to regulate osteogenesis or osteoclast differentiation. We review the classification of these E3 enzymes and the mechanisms that influence upstream and downstream molecules and transduction pathways. Finally, this paper reviews the discovery of the relevant UPS inhibitors, drug molecules, and noncoding RNAs so far and prospects the future research and treatment.

Ferroptosis is an iron-dependent form of programmed cell death and an important type of biological catabolism. Through the action of divalent iron or ester oxygenase, ferroptosis can induce lipid peroxidation and cell death, regulating a variety of physiological processes. The role of ferroptosis in the modulation of bone homeostasis is a significant topic of interest. Herein, we review and discuss recent studies exploring the mechanisms and functions of ferroptosis in different bone-related cells, including mesenchymal stem cells, osteoblasts, osteoclasts, and osteocytes. The association between ferroptosis and disorders of bone homeostasis is also explored in this review. Overall, we aim to provide a detailed overview of ferroptosis, summarizing recent understanding on its role in regulation of bone physiology and bone disease pathogenesis.

Lower extremity deep vein thrombosis (DVT) is one of the main complications in patients with traumatic fractures, and for severe patients, the DVT can even affect arterial blood supply, resulting in insufficient limb blood supply. If the thrombus breaks off, pulmonary embolism may occur, with a high mortality. The treatment and rehabilitation strategies of thrombosis in patients with lower extremity fractures have its particularity. DVT in traumatic fractures patients has attracted extensive attention and been largely studied, and the measures for prevention and treatment of DVT are constantly developing. In recent years, a series of thrombosis prevention and treatment guidelines have been updated at home and abroad, but there are still many doubts about the prevention and treatment of DVT in patients with different traumatic fractures. Accordingly, on the basis of summarizing the latest evidence-based medical evidence at home and abroad and the clinical experience of the majority of experts, the authors summarize the clinical treatment and prevention protocols for DVT in patients with traumatic fractures, and make this consensus on the examination and assessment, treatment, prevention and preventive measures for DVT in patients with different fractures so as to provide a practicable approach suitable for China ′s national conditions and improve the prognosis and the life quality of patients.

Patients with Huntington’s disease (HD) have an increased incidence of diabetes. However, the molecular mechanisms of pancreatic β-cell dysfunction have not been entirely clarified. Revealing the pathogenesis of diabetes can provide a novel understanding of the onset and progression of HD, as well as potential clues for the development of new therapeutics. Here, we demonstrated that the mouse pancreatic insulinoma cell line NIT-1 expressing N-terminal mutant huntingtin (mHTT) containing 160 polyglutamine (160Q cells) displayed lower cell proliferative ability than the cells expressing N-terminal wild-type HTT containing 20 polyglutamine (20Q cells). In addition, 160Q cells were more prone to apoptosis and exhibited deficient glucose-stimulated insulin expression and secretion. Furthermore, insulin signaling molecule insulin receptor substrate 2 (IRS-2) expression decreased and was recruited into mHTT aggregates. Consequently, glucose stimulation failed to activate the downstream molecule phosphatidylinositol-3 kinase (PI3K) in 160Q cells, leading to reduced phosphorylation levels of serine–threonine protein kinase AKT and forkhead box protein O1 (FoxO1). These data indicate that activation of the glucose-stimulated PI3K/AKT/FoxO1 signaling pathway is significantly blocked in pancreatic β-cells in HD. Importantly, insulin treatment inhibited the aggregation of mHTT and significantly improved the activation of PI3K/AKT/FoxO1 signaling in 160Q cells. These results suggest that the inhibition of the PI3K/AKT/FoxO1 pathway might be due to the recruitment of IRS-2 into mHTT aggregates in HD β-cells, ultimately contributing to the impairment of pancreatic β-cells. In conclusion, our work provides new insight into the underlying mechanisms of the high incidence of diabetes and abnormal glucose homeostasis in HD.