Biomaterials最新文献

The senescence of mesenchymal stem cells (MSCs) leads to the significant change of their metabolic activity and physiological behaviors. In the context of orthopedic treatment, the osteointegration of titanium implant is largely affected by MSC aging, imposing considerable limitations on its long-term application. In this study, a surface modification on titanium implants was designed to enhance osteointegration by effectively regulating the functions of senescent MSC: A typical micro-nano topological structure was established on the implant surface to improve the osteogenic differentiation of MSCs. Then a functional hydrogel coating was covalently modified to the implant surface through a poly-dopamine layer. For senescent MSCs, firstly, the coating can eliminate the activation of senescence-associated secretory phenotype (SASP) of senescent MSCs by micro-nano topological structure, and it accelerated the proliferation of non-senescent MSCs by the reactive oxygen species (ROS) scavenging. With the degradation of the hydrogel coating, the composition of stem cell pool around the implant interfaces gradually rejuvenated, as the number of non-senescent MSCs increased and senescent MSCs decreased. Meanwhile, the exposed micro-nano topological structure showed significant effect on the osteogenic differentiation of MSCs, and ultimately promoted the osteointegration in aging rats. These results provided promising insights for the design and application of orthopedic titanium implants for aging patients.

Chronic diabetic wounds are characterized by hypoxia, persistent microbial infection, and impaired healing, posing significant challenges to conventional therapies. Herein, we present a novel sprayable double-network hydrogel platform designed to achieve efficient antimicrobial activity and accelerated wound repair under hypoxic conditions by leveraging a type I photodynamic therapy (PDT) and immune-metabolic regulatory strategy. Specifically, we employ salvianolic acid B (SAB) to form a self-assembled hydrogel (SAB-gel) and incorporate fibrin to construct a robust and acidic double-network SAB/F-gel with enhanced mechanical strength and acidic environment. Concurrently, thymoquinone (TQ) and chlorin e6 (Ce6) are self-assembled via hydrophobic interactions to form TQ/Ce6 nanoparticles (TQ/Ce6 NPs) and embedded in the SAB/F-gel, to fabricate the TQ/Ce6@SAB/F-gel. Under low-oxygen conditions, TQ acts as an electron-transfer mediator, enabling Ce6 to generate abundant superoxide anions (·O₂^-) via type I PDT under red light (RL) irradiation. These ·O₂^- are subsequently converted into hydrogen peroxide (H₂O₂) and hydroxyl radicals (·OH) in the acidic environment provided by acidic SAB/F-gel, thereby reducing the dependence on oxygen and maintaining potent antimicrobial efficacy against MRSA, Pseudomonas aeruginosa (Pa), Acinetobacter baumannii (Ab), Escherichia coli (E. coli) and Candida albicans (Ca). In vitro experiments demonstrated that TQ/Ce6@SAB/F-gel regulates macrophage M2 polarization and promotes endothelial cell proliferation, migration, and tube formation via the immune-metabolic regulatory pathways. When applied to MRSA-infected diabetic wounds in mice, the hydrogel in combination with RL completely eradicated bacteria, promoted collagen deposition and angiogenesis, and significantly accelerated wound closure, as demonstrated by histological examination and transcriptome sequencing. This work offers a versatile, biocompatible, and oxygen-independent PDT-based hydrogel system for the treatment of refractory infected diabetic wounds, offering potential for clinical translation and improved patient outcomes.

Osteoarthritis (OA), a prevalent degenerative joint disease, currently lacks effective therapeutic options beyond symptomatic relief. Persistent inflammation and impaired cartilage repair accelerate the disease progression. The enzyme inducible nitric oxide synthase (iNOS) contributes to OA by producing nitric oxide (NO), which intensifies inflammation and inhibits cartilage regeneration. Traditional iNOS inhibitors have demonstrated limited efficacy due to inadequate targeted release and uncoordinated control over inflammation. In this study, we developed a self-supported DNAzyme-based DNA hydrogel using rolling circle amplification (RCA) technology to deliver iNOS-targeting DNAzymes and bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) in response to inflammation. The hydrogel incorporates triglycerol monostearate nanoparticles (TGMS NPs), which degrade under high matrix metalloproteinase (MMP) levels in OA joints, thereby triggering the release of the DNAzymes and exosomes with precision. This targeted delivery modulates the inflammatory microenvironment by reducing pro-inflammatory NO production and supports chondrogenesis by promoting M2 macrophage polarization. In vitro and in vivo analyses reveal that the hydrogel significantly reduces inflammatory cytokine levels, enhances chondrocyte proliferation, and restores extracellular matrix integrity, ultimately slowing OA progression. This smart hydrogel offers a promising ambidextrous strategy for microenvironment modulation and cartilage regeneration, potentially advancing OA treatment.