Polysaccharide hydrogels for skin wound healing.

Advances in the development and utilization of polysaccharide materials are highly promising, offering prominent applications in the field of tissue engineering for addressing diverse clinical needs, including wound healing, bone regeneration, cartilage repair, and treatment of conditions such as arthritis. Novel polysaccharide materials are popular owing to their inherent stability, biocompatibility, and repeatability. This review presents an overview of the biomedical applications of natural polysaccharide hydrogels and their derivatives. Herein, we discuss the latest advancements in the fabrication, physicochemical properties, and biomedical applications of polysaccharide-based hydrogels, including chitosan, hyaluronic acid, alginate, and cellulose. Various processing techniques applicable to polysaccharide materials are explored, such as the transformation of polysaccharide hydrogels into electrospun nanofibers, microneedles, microspheres, and nanogels. Furthermore, the use of polysaccharide hydrogels in the context of wound-healing applications, including hemostatic effects, antimicrobial activities, anti-inflammatory properties, and promotion of angiogenesis, is presented. Finally, we address the challenges encountered in the development of polysaccharide hydrogels and outline the potential prospects in this evolving field.

Functional Nanomaterials for the Treatment of Osteoarthritis.

Osteoarthritis (OA) is the most common degenerative joint disease, affecting more than 595 million people worldwide. Nanomaterials possess superior physicochemical properties and can influence pathological processes due to their unique structural features, such as size, surface interface, and photoelectromagnetic thermal effects. Unlike traditional OA treatments, which suffer from short half-life, low stability, poor bioavailability, and high systemic toxicity, nanotherapeutic strategies for OA offer longer half-life, enhanced targeting, improved bioavailability, and reduced systemic toxicity. These advantages effectively address the limitations of traditional therapies. This review aims to inspire researchers to develop more multifunctional nanomaterials and promote their practical application in OA treatment.

Antibacterial sequential growth factor delivery from alginate/gelatin methacryloyl microspheres for bone regeneration.

Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.

Silk Fibroin Microneedles Loaded with Lipopolysaccharide-Pretreated Bone Marrow Mesenchymal Stem Cell-Derived Exosomes for Oral Ulcer Treatment.

Oral ulcers, superficial lesions on the surface of the oral mucosa, have a high incidence rate, and their main symptoms include local pain and erosion. Lipopolysaccharide (LPS)-preconditioned bone marrow mesenchymal stem cells and their secreted exosomes (LPS-pre-Exos) have been shown to promote recovery in various inflammatory conditions and wounds. However, studies documenting LPS-pre-Exos as a therapeutic intervention for oral mucosal-like diseases are lacking. In this study, we prepared a silk fibroin microneedle (MN) patch consisting of LPS-pre-Exos and zeolitic imidazolate framework-8 (ZIF-8) that localized at the tip and base, respectively, and used this MN patch for oral ulcer treatment. Upon insertion into the oral mucosa, continuous LPS-pre-Exos release was observed, which promoted macrophage polarization and tissue healing. Additionally, the ZIF-8 framework in the MN patch facilitated the controlled release of Zn2+, which demonstrated potent antimicrobial properties via synergistic effects. The in vitro experimental results showed that the silk fibroin MN patch can continuously release LPS-pre-Exos and Zn2+ for more than 7 days. Thus, the LPS-pre-Exos and ZIF-8-loaded silk fibroin MN patch exhibited good anti-inflammatory and antibacterial properties, promoting oral ulcer healing, and showed good histocompatibility. Hence, it may represent a potentially valuable strategy for facilitating oral ulcer healing.

Advances in natural and synthetic macromolecules with stem cells and extracellular vesicles for orthopedic disease treatment.

Serious orthopedic disorders resulting from myriad diseases and impairments continue to pose a considerable challenge to contemporary clinical care. Owing to its limited regenerative capacity, achieving complete bone tissue regeneration and complete functional restoration has proven challenging with existing treatments. By virtue of cellular regenerative and paracrine pathways, stem cells are extensively utilized in the restoration and regeneration of bone tissue; however, low survival and retention after transplantation severely limit their therapeutic effect. Meanwhile, biomolecule materials provide a delivery platform that improves stem cell survival, increases retention, and enhances therapeutic efficacy. In this review, we present the basic concepts of stem cells and extracellular vesicles from different sources, emphasizing the importance of using appropriate expansion methods and modification strategies. We then review different types of biomolecule materials, focusing on their design strategies. Moreover, we summarize several forms of biomaterial preparation and application strategies as well as current research on biomacromolecule materials loaded with stem cells and extracellular vesicles. Finally, we present the challenges currently impeding their clinical application for the treatment of orthopedic diseases. The article aims to provide researchers with new insights for subsequent investigations.

Multifunctional hyaluronic acid/gelatin methacryloyl core-shell microneedle for comprehensively treating oral mucosal ulcers.

Oral ulceration is the most common oral mucosal disease. Oral mucosal ulcers are extremely painful, may interfere with eating and speaking, and potentially complicate systemic symptoms in severe cases. The humid and highly dynamic environment of the oral cavity makes local drug administration for treating oral mucosal ulcers challenging. To overcome these challenges, we designed and prepared a novel dissolving microneedle (MN) patch containing multiple drugs in a core-shell to promote oral ulcer healing. The MNs contained a methacrylate gelatin shell layer of basic fibroblast growth factor (bFGF), a hyaluronic acid (HA) core loaded with dexamethasone (DXMS), and zeolite imidazoline framework-8 (ZIF-8) encapsulated in the HA-based backplane. Progressive degradation of gelatin methacryloyl (GelMA) from the tip of the MN patch in the oral mucosa resulted in sustained bFGF release at the lesion site, significantly promoting cell migration, proliferation, and angiogenesis. Moreover, the rapid release of HA and, subsequently, DXMS inhibited inflammation, and the remaining MN backing after the tip dissolved behaved as a dressing, releasing ZIF-8 for its antimicrobial effects. This novel, multifunctional, transmucosal core-shell MN patch exhibited excellent anti-inflammatory, antimicrobial, and pro-healing effects in vivo and in vitro, suggesting that it can promote oral ulcer healing.

Multifunctional self-healing peptide hydrogel for wound healing.

The complete healing of wounds remains a challenge in clinical care. In addition, various complications such as inflammation and infection that may occur during skin wound healing can impede the healing process. Here, we constructed a multifunctional self-repairing hydrogel by utilizing Schiff base bonds. This hydrogel exhibited good self-healing properties and could cope with destructive external influences. The self-healing hydrogel was injectable, ensuring that the hydrogel dressing adhered to the wound. Carboxymethyl chitosan and oxidized chondroitin sulfate demonstrated good biocompatibility and multiple bioactivities and were successfully used to prepare self-healing hydrogels. Meanwhile, the SIKVAV biopeptide was less expensive and more morphologically stable than vascular endothelial growth factor and had a high pro-angiogenic activity. Thus, the SIKVAV biopeptide was cross-linked to the oxidized chondroitin sulfate of the hydrogel through covalent bonding to avoid rapid biopeptide degradation, achieving a slow release of the drug. This peptide hydrogel exhibited good biocompatibility and antimicrobial properties; moreover, experiments conducted on mice revealed that it could effectively promote angiogenesis and skin tissue repair. These findings suggest that the injectable self-repairing peptide hydrogel may facilitate skin wound healing and other applications.

Antibacterial microneedle patch releases oxygen to enhance diabetic wound healing.

Cell growth and metabolism require an adequate supply of oxygen. However, obtaining sufficient oxygen from the blood circulating around diabetic wounds is challenging. Nevertheless, achieving a continuous and stable oxygen supply is required for these wounds to heal. Hence, in this study, we report a novel antibacterial oxygen-producing silk fibroin methacryloyl hydrogel microneedle (MN) patch comprising tips encapsulated with calcium peroxide and catalase and a base coated with antibacterial Ag nanoparticles (AgNPs). The tip of the MN patch continuously releases oxygen and inhibits the production of reactive oxygen species. This accelerates diabetic wound healing by promoting cellular accretion and migration, macrophage M2 polarization, and angiogenesis. The AgNPs at the base of the MN patch effectively combat microbial infection, further facilitating wound repair. These findings suggest that using this multifunctional oxygen-producing MN patch may be a promising strategy for diabetic wound healing in clinical settings.

Construction of intelligent drug delivery system based on polysaccharide-derived polymer micelles: A review.

Micelles are nanostructures developed via the spontaneous assembly of amphiphilic polymers in aqueous systems, which possess the advantages of high drug stability or active-ingredient solubilization, targeted transport, controlled release, high bioactivity, and stability. Polysaccharides have excellent water solubility, biocompatibility, and degradability, and can be modified to achieve a hydrophobic core to encapsulate hydrophobic drugs, improve drug biocompatibility, and achieve regulated delivery of the loaded drug. Micelles drug delivery systems based on polysaccharides and their derivatives show great potential in the biomedical field. This review discusses the principles of self-assembly of amphiphilic polymers and the formation of micelles; the preparation of amphiphilic polysaccharides is described in detail, and an overview of common polysaccharides and their modifications is provided. We focus on the review of strategies for encapsulating drugs in polysaccharide-derived polymer micelles (PDPMs) and building intelligent drug delivery systems. This review provides new research directions that will help promote future research and development of PDPMs in the field of drug carriers.

3D printed scaffolds based on hyaluronic acid bioinks for tissue engineering: a review.

Hyaluronic acid (HA) is widely distributed in human connective tissue, and its unique biological and physicochemical properties and ability to facilitate biological structure repair make it a promising candidate for three-dimensional (3D) bioprinting in the field of tissue regeneration and biomedical engineering. Moreover, HA is an ideal raw material for bioinks in tissue engineering because of its histocompatibility, non-immunogenicity, biodegradability, anti-inflammatory properties, anti-angiogenic properties, and modifiability. Tissue engineering is a multidisciplinary field focusing on in vitro reconstructions of mammalian tissues, such as cartilage tissue engineering, neural tissue engineering, skin tissue engineering, and other areas that require further clinical applications. In this review, we first describe the modification methods, cross-linking methods, and bioprinting strategies for HA and its derivatives as bioinks and then critically discuss the strengths, shortcomings, and feasibility of each method. Subsequently, we reviewed the practical clinical applications and outcomes of HA bioink in 3D bioprinting. Finally, we describe the challenges and opportunities in the development of HA bioink to provide further research references and insights.

Self-healing hydrogels based on biological macromolecules in wound healing: A review.

The complete healing of skin wounds has been a challenge in clinical treatment. Self-healing hydrogels are special hydrogels formed by distinctive physicochemically reversible bonds, and they are considered promising biomaterials in the biomedical field owing to their inherently good drug-carrying capacity as well as self-healing and repair abilities. Moreover, natural polymeric materials have received considerable attention in skin tissue engineering owing to their low cytotoxicity, low immunogenicity, and excellent biodegradation rates. In this paper, we review recent advances in the design of self-healing hydrogels based on natural polymers for skin-wound healing applications. First, we outline a variety of natural polymers that can be used to construct self-healing hydrogel systems and highlight the advantages and disadvantages of different natural polymers. We then describe the principle of self-healing hydrogels in terms of two different crosslinking mechanisms-physical and chemical-and dissect their performance characteristics based on the practical needs of skin-trauma applications. Next, we outline the biological mechanisms involved in the healing of skin wounds and describe the current application strategies for self-healing hydrogels based on these mechanisms. Finally, we analyze and summarize the challenges and prospects of natural-material-based self-healing hydrogels for skin applications.

Hydrogel-based treatments for spinal cord injuries.

Spinal cord injury (SCI) is characterized by damage resulting in dysfunction of the spinal cord. Hydrogels are common biomaterials that play an important role in the treatment of SCI. Hydrogels are biocompatible, and some have electrical conductivity that are compatible with spinal cord tissues. Hydrogels have a high drug-carrying capacity, allowing them to be used for SCI treatment through the loading of various types of active substances, drugs, or cells. We first discuss the basic anatomy and physiology of the human spinal cord and briefly discuss SCI and its treatment. Then, we describe different treatment strategies for SCI. We further discuss the crosslinking methods and classification of hydrogels and detail hydrogel biomaterials prepared using different processing methods for the treatment of SCI. Finally, we analyze the future applications and limitations of hydrogels for SCI. The development of biomaterials opens up new possibilities and options for the treatment of SCI. Thus, our findings will inspire scholars in related fields and promote the development of hydrogel therapy for SCI.

Applications of human and bovine serum albumins in biomedical engineering: A review.

Serum albumin, commonly recognized as a predominant major plasma protein, is ubiquitously distributed among vertebrates, demonstrating versatility and widespread accessibility. Numerous studies have discussed the composition and attributes of human and bovine serum albumin; nonetheless, few systematic and comprehensive summaries on human and bovine serum albumin exist. This paper reviews the applications of human and bovine serum albumin in biomedical engineering. First, we introduce the differences in the structure of human and bovine serum albumin. Next, we describe the extraction methods for human and bovine serum albumin (fractionation process separation, magnetic adsorption, reverse micellar (RM) extraction, and genetic engineering) and the advantages and disadvantages of recently developed extraction methods. The characteristics of different processing forms of human and bovine serum albumin are also discussed, concomitantly elucidating their intrinsic properties, functions, and applications in biomedicine. Notably, their pivotal functions as carriers for drugs and tissue-engineered scaffolds, as well as their contributions to cell reproduction and bioimaging, are critically examined. Finally, to provide guidance for researchers in their future work, this review summarizes the current state of human and bovine serum albumin research and outlines potential future research topics.

Zn2+ incorporated composite polysaccharide microspheres for sustained growth factor release and wound healing.

The development of new wound dressings has always been an issue of great clinical importance and research promise. In this study, we designed a novel double cross-linked polysaccharide hydrogel microspheres based on alginate (ALG) and hyaluronic acid methacrylate (HAMA) from gas-assisted microfluidics for wound healing. The microspheres from gas-assisted microfluidics showed an uniform size and good microsphere morphology. Moreover, this composite polysaccharide hydrogel microspheres were constructed by harnessing the fact that zinc ions (Zn2+) can cross-link with ALG as well as histidine-tagged vascular endothelial growth (His-VEGF) to achieve long-term His-VEGF release, thus promoting angiogenesis and wound healing. Meanwhile, Zn2+, as an important trace element, can exert antibacterial and anti-inflammatory effects, reshaping the trauma microenvironment. In addition, photo cross-linked HAMA was introduced into the microspheres to further improve its mechanical properties and drug release ability. In summary, this novel Zn2+ composite polysaccharide hydrogel microspheres loaded with His-VEGF based on a dual cross-linked strategy exhibited synergistic antimicrobial and angiogenic effects in promoting wound healing.

Sitagliptin attenuates neuronal apoptosis via inhibiting the endoplasmic reticulum stress after acute spinal cord injury.

Regulation of endoplasmic reticulum stress (ER) stress-induced apoptosis and nerve regeneration is a hopeful way for acute spinal cord injury (SCI). Sitagliptin (Sita) is one of dipeptidyl peptidase-4 (DPP-4) inhibitor, which is beneficial neurons damaged diseases. However, its protective mechanisms of avoiding nerve injury remain unclear. In this study, we further investigated the mechanism of the anti-apoptotic and neuroprotective effects of Sita in promoting locomotor recovery from SCI. In vivo results showed that Sita treatment reduced neural apoptosis caused by SCI. Moreover, Sita effectively attenuated the ER tress and associated apoptosis in rats with SCI. A striking feature was the occurrence of nerve fiber regeneration at the lesion site, which eventually led to significant locomotion recovery. In vitro results showed that the PC12 cell injury model induced by Thapsigargin (TG) also showed similar neuroprotective effects. Overall, sitagliptin showed potent neuroprotective effects by targeting the ER stress-induced apoptosis both in vivo and vitro, thus facilitating the regeneration of the injured spinal cord.

Prognostic Model of Eleven Genes Based on the Immune Microenvironment in Patients With Thymoma.

Purpose: The pathogenesis of thymoma (THYM) remains unclear, and there is no uniform measurement standard for the complexity of THYM derived from different thymic epithelial cells. Consequently, it is necessary to develop novel biomarkers of prognosis estimation for patients with THYM. Methods: Consensus clustering and single-sample gene-set enrichment analysis were used to divide THYM samples into different immunotypes. Differentially expressed genes (DEGs) between those immunotypes were used to do the Kyoto Encyclopedia of Genes and Genomes analysis, Gene Ontology annotations, and protein-protein interaction network. Furthermore, the survival-related DEGs were used to construct prognostic model with lasso regression. The model was verified by survival analysis, receiver operating characteristic curve, and principal component analysis. Furthermore, the correlation coefficients of stemness index and riskscore, tumor mutation burden (TMB) and riskscore, drug sensitivity and gene expression were calculated with Spearman method. Results: THYM samples were divided into immunotype A and immunotype B. A total of 707 DEGs were enriched in various cancer-related or immune-related pathways. An 11-genes signature prognostic model (CELF5, ODZ1, CD1C, DRP2, PTCRA, TSHR, HKDC1, KCTD19, RFX8, UGT3A2, and PRKCG) was constructed from 177 survival-related DEGs. The prognostic model was significantly related to overall survival, clinical features, immune cells, TMB, and stemness index. The expression of some genes were significantly related to drug sensitivity. Conclusion: For the first time, a prognostic model of 11 genes was identified based on the immune microenvironment in patients with THYM, which may be helpful for diagnosis and prediction. The associated factors (immune microenvironment, mutation status, and stemness) may be useful for exploring the mechanisms of THYM.

3D printed polycaprolactone/beta-tricalcium phosphate/magnesium peroxide oxygen releasing scaffold enhances osteogenesis and implanted BMSCs survival in repairing the large bone defect.

Ischemia and hypoxia in the bone defect area remain an intractable problem when treating large bone defects. Thus, oxygen-releasing biomaterials have been widely researched in recent years. Magnesium peroxide (MgO2) can release oxygen (O2), and magnesium ions (Mg2+), simultaneously, which is seen to have significant potential in bone substitutes. In this study, we used 3D printing technology to fabricate a MgO2-contained composite scaffold, which was composed of polycaprolactone (PCL), beta-tricalcium phosphate (ß-TCP) and magnesium peroxide (MgO2). Physical properties and O2/Mg2+ releasing behavior of the scaffold were studied. Then, we evaluated the effects of the scaffold on cell survival, proliferation, migration, adhesion and osteogenic differentiation by the co-culture of bone marrow mesenchymal stem cells (BMSCs) and scaffold under normoxia and hypoxia in vitro. Finally, the osteogenic properties of the scaffold in vivo were evaluated via the rat femoral condylar bone defect model. The PCL/ß-TCP/MgO2 scaffold showed good mechanical properties and sustained O2 and Mg2+ release for about three weeks. Meanwhile, the scaffold showed appreciable promotion on the survival, proliferation, migration and osteogenic differentiation of BMSCs under hypoxia compared with control groups. The results of imaging studies and histological analysis showed that implantation of PCL/ß-TCP/MgO2 scaffold could promote seed cell survival and significantly increased new bone formation. In sum, the PCL/ß-TCP/MgO2 scaffold is promising with great potential for treating large bone defects.

Effect of synthetic oxygen-generating system on cell survival under hypoxic condition in vitro.

A significant challenge in the tissue engineering of injured sites is the lack of vascularization in the engineered sites due to insufficient oxygen supply. A scaffolding system is required to support seeded cells as vascularization develops. In this study, we examined the effects of hypoxic conditions and oxygen release on cell survival in a synthetic system. We developed a three-dimensional system using CaO2/poly(lactic-co-glycolic acid) microspheres suspended in a hydrogel. The system material was evaluated using stem cells under hypoxic conditions alongside controls to evaluate its oxygen-generating potential over a period of 21 days. The hydrogel acted as a flexible carrier supporting cell attachment and growth, protecting microspheres, and prolonging oxygen release. The system generated oxygen and supported cell growth, which are together expected to promote stem cell survival and growth in the weeks following implantation.

Effects of oxygen generating scaffolds on cell survival and functional recovery following acute spinal cord injury in rats.

Persistent local oxygen delivery is crucial to create a microenvironment for cell survival and nerve regeneration in acute spinal cord injury (SCI). This study aimed to fabricate calcium peroxide-based microspheres incorporated into a 3-D construct scaffold as a novel oxygen release therapy for SCI. The scaffolds were able to generate oxygen over the course of 21 days when incubated under hypoxic conditions. In vitro, GFP-labeled bone marrow-derived mesenchymal stem cells (MSCs) were planted into the scaffolds. We observed that scaffolds could enhance MSC survival under hypoxic conditions for more than 21 days. Oxygen generating scaffolds were transplanted into spinal cord injury sites of rats in vivo. Twelve weeks following transplantation, cavity areas in the injury/graft site were significantly reduced due to tissue regeneration. Additionally, the oxygen generating scaffolds improved revascularization as observed through vWF immunostaining. A striking feature was the occurrence of nerve fiber regeneration in the lesion sites, which eventually led to significant locomotion recovery. The present results indicate that the oxygen generating scaffolds have the property of sustained local oxygen release, thus facilitating regeneration in injured spinal cords.

Comparison of different bone graft with arthroscopy-assisted arthrodesis for the treatment of traumatic arthritis of the subtalar joint.

AIM OF THE STUDY: To compare the clinical outcomes of traumatic arthritis of the subtalar joint treated by arthroscopy-assisted arthrodesis with autologous bone graft, allogenous bone graft, artifical bone graft, and no bone graft . METHODS: Sixty-two patients (64 ft) with traumatic arthritis of subtalar joint were randomly divided into four groups. The cases treated with arthroscopy-assisted arthrodesis were analyzed retrospectively. The mean follow-up time was about 22 months (18-28 months) in each group. Clinical outcomes were assessed by the American Orthopaedic Foot and Ankle Society (AOFAS) score, Visual Analog Scale (VAS), and radiographic examination. The post-operative complications in each group were recorded respectively. RESULTS: All operations were successful, without incision complications. The subtalar joint obtained full osseous fusion in each group. The average time of osseous fusion was about 12 weeks. There was no significant difference in the fusion time with each group (P = 0.991). The AOFAS and VAS scores in each group were improved significantly in the pre-operative vs post-operative evaluation (all P < 0.01). The average operation time in autologous bone graft group was 74.56 ± 11.45 min which significantly different from that of other groups(P < 0.01). CONCLUSION: Similar clinical outcomes were achieved among each type of bone graft. Therefore, which types of bone graft or not may be not the most important for arthroscopy-assisted subtalar arthrodesis.