Biomaterials research最新文献

Cancer continues to pose remarkable medical challenges worldwide. While current cancer therapies can lead to initial clinical improvement, they are often followed by recurrence, metastasis, and drug resistance, underscoring the urgent need for innovative treatment strategies. Atorvastatin calcium (AC), a widely used lipid-lowering and anti-inflammation drug in the clinic, has shown antitumor potential. To further improve the antitumor efficacy, we developed self-assembled AC and polydopamine (PDA) nanoparticles whose surface was coated with macrophage membranes (CM) as a biomimetic drug delivery system [AC@PDA@CM (APM)]. APM showed high drug-loading capacity, excellent stability, excellent bioavailability, and tumor-targeting ability, ultimately achieving photothermal synergistic cancer immunotherapy. Our findings indicate that APM efficiently delivers AC to tumor sites while leveraging photothermal therapy (PTT) to enhance local tumor ablation and antitumor immune effect. Notably, APM mitigates tumor immunosuppression triggered by PTT through AC, suppressing the COX-2/PGE2 pathway and immune evasion signal CD47. Furthermore, APM notably reduced nonspecific distribution and side effects, which is conducive to ensuring the safety level of medication. This integrated approach boosts therapeutic efficacy and highlights the potential of APM as a multifunctional agent for cancer therapy, paving the way for future clinical applications.

Advancing at the cutting edge of oncology, the synergistic application of photothermal therapy coupled with immunotherapy is rapidly establishing itself as an innovative and potent strategy against cancer. A critical challenge in this domain is the precise and efficient targeting of tumor tissues with photothermal agents and immunoadjuvants while minimizing interference with healthy tissues. In this paper, we introduce an ingenious biomimetic nanoparticle platform, cancer cell membrane coated F127/(R837 and IR1048) (CFRI) nanoparticles encapsulating a near-infrared region II photothermal agent, IR1048, and an immunostimulatory molecule, R837, with their surface modified using membranes derived from tumor cells, conferring exceptional specificity for tumor targeting. CFRI nanoparticles demonstrated an extraordinary photothermal conversion efficiency of 49%, adeptly eradicating in situ tumors. This process also triggered the release of damage-associated molecular patterns, thereby activating dendritic cells and catalyzing the maturation and differentiation of T cells, initiating a robust immune response. In vivo animal models substantiated that the CFRI-mediated synergistic photothermal and immunotherapeutic strategy markedly suppressed the proliferation of in situ tumors and provoked a vigorous systemic immune response, effectively curtailing the metastasis and recurrence of distant tumors. The successful development of the CFRI nanoparticle system offers a promising horizon for future clinical translations and pioneering research in oncology.

The treatment of infected wounds is often complicated by bacterial infection and impaired scar healing. Antibiotics and growth factors are typically utilized to address these clinical challenges and expedite wound healing. However, the use of hydrogels containing these therapeutic agents is often restricted to complex cases and increases treatment costs considerably. In this study, we developed a quaternized-chitosan-based hybrid hydrogel dressing (SQFB) with intrinsic antibacterial properties to address these limitations. The hybrid hydrogel contained interpenetrating polymer networks of basic fibroblast growth factor and black phosphorus nanosheets, facilitating a photothermal response that triggers the release of basic fibroblast growth factor upon near-infrared irradiation. In vitro experiments demonstrated that SQFB exhibits superior antibacterial, hemostatic, enhanced cell proliferation, and angiogenesis functions. Importantly, the results showed that SQFB can promote the healing of infected wounds by accelerating all 4 stages of wound repair while preventing scarring formation. RNA sequencing analysis revealed that combined treatment with SQFB and near-infrared irradiation can effectively modulate genes primarily associated with epithelial regeneration pathways and metabolic processes. Collectively, our findings suggest that this hybrid hydrogel holds great promise for the effective management of infected wounds.

Intervertebral disc degeneration (IDD) process is accompanied by overactive inflammation and mechanical instability of the nucleus pulposus (NP). Current treatments do not fully restore the biomechanical environment of discs, limiting their therapeutic efficacy. Thus, novel strategies are required to combat IDD. Hydrogels have outstanding biocompatibility and mechanical properties, most importantly, absorbing and retaining water similar to human NP tissue, showing a unique superiority in the treatment of IDD. In this study, we employed a viscoelastic ionic hydrogel (VIG) composed of polyvinyl alcohol and magnesium ions to investigate the therapeutic effect for IDD. VIG demonstrated an optimal degradation rate and NP-biomimetic swelling behavior in vitro. In the rat model of IDD, VIG-injected discs demonstrated mechanical properties approximating those of native discs, including stiffness, relaxation, and dissipation capacity. Furthermore, finite element analysis demonstrated that VIG improved biomechanical function of degenerated discs. VIG effectively inhibited the progression of IDD in the rat model by increasing extracellular matrix synthesis and decreasing matrix metalloproteinase-13 (MMP-13) expression. Moreover, VIG promoted proliferation and differentiation of NP cells in response to extracellular mechanical changes through the integrin-YAP signaling pathway. These findings suggest that VIG has the potential to modulate the NP inflammatory microenvironment and restore mechanical stability in IDD. This work represents a straightforward and promising strategy for IDD treatment.

Tumors are the second most common cause of mortality globally, ranking just below heart disease. With continuous advances in diagnostic technology and treatment approaches, the survival rates of some cancers have increased. Nevertheless, due to the complexity of the mechanisms underlying tumors, cancer remains a serious public health issue that threatens the health of the population globally. Manganese (Mn) is an essential trace element for the human body. Its regulatory role in tumor biology has received much attention in recent years. Developments in nanotechnology have led to the emergence of Mn-based nanoparticles that have great potential for use in the diagnosis and treatment of cancers. Mn-based nanomaterials can be integrated with conventional techniques, including chemotherapy, radiation therapy, and gene therapy, to augment their therapeutic effectiveness. Further, Mn-based nanomaterials can play a synergistic role in emerging treatment strategies for tumors, such as immunotherapy, photothermal and photodynamic therapy, electromagnetic hyperthermia, sonodynamic therapy, chemodynamic therapy, and intervention therapy. Moreover, Mn-based nanomaterials can enhance both the precision of tumor diagnostics and the capability for combined diagnosis and treatment. This article examines the roles and associated mechanisms of Mn in the field of physiology and tumor biology, with a focus on the application prospects of Mn-based nanomaterials in tumor diagnosis and treatment.

Periodontal regenerative medicine is currently undergoing a paradigm shift from dissecting the healing process toward utilization of the developmental program. Biological hydroxyapatite (BHA), a major component of guided tissue regeneration, has long been optimized for inducing multidirectional differentiation of periodontal ligament cells (PDLCs). However, this approach runs counter to the redevelopment strategy. Thus, the conventional BHA should evolve to induce the redevelopment process of periodontal tissue. In this study, histopathological changes and immune microenvironment characteristics of the periodontal developmental process, natural healing process (Blank group), and BHA-mediated healing process (BHA group) were compared to evaluate the main manifestations of BHA-mediated periodontal "developmental engineering" outcome. Our results suggested that neither the Blank nor BHA group could recur key events in periodontal development. The implantation of BHA led to pro-inflammatory immune microenvironment and an unstable blood fibrin clot structure, which facilitated the invasion of outer gingival fibroblasts, consequently disrupting redevelopmental events. High-throughput chip technology was further used to explore the underlying mechanism of immune activation, revealing that the calcium-NOD-like receptor-inflammation axis signaling axis promoted the activation of pro-inflammatory immune response that contributed to redevelopment failure. An immunomodulatory cytokine interleukin 4 (IL4)-modified BHA was used to further validate the efficacy of developmental engineering strategy. IL4 could partially rescued the redevelopment failure through immunosuppression. This study presented an innovative strategy for the development of advanced periodontal regenerative materials and offered a potential approach for the application of development-inspired periodontal tissue engineering strategies. It represented a marked advancement in the development of regenerative medicine and propelled the clinical organ restoration forward.

Cancer remains a major concern for human health worldwide. To fight the curse of cancer, boron neutron capture therapy is an incredibly advantageous modality in the treatment of cancer as compared to other radiotherapies. Due to tortuous vasculature in and around tumor regions, boron (¹⁰B) compounds preferentially house into tumor cells, creating a large dose gradient between the highly mingled cancer cells and normal cells. Epithermal or thermal neutron bombardment leads to tumor-cell-selective killing due to the generation of heavy particles yielded from in situ fission reaction. However, the major challenges for boron nanocomposites' development have been from the synthesis part as well as the requirement for selective cancer targeting and the delivery of therapeutic concentrations of boron (¹⁰B) with nominal healthy tissue accumulation and retention. To circumvent the above challenges, this review discusses boride nanocomposite design, safety, and biocompatibility for biomedical applications for general public use. This review sparks interest in using boron nanocomposites as boron neutron capture therapy agents and repurposing them in comorbidity treatments, with future scientific challenges and opportunities, with a hope to accelerate the stimulus of developing possible boron composite nanomedicine research and applications worldwide.

Senescent chondrocytes, which are increased in osteoarthritic (OA) cartilage, promote cartilage defects and the senescent knee microenvironment by inducing senescence to surrounding normal chondrocytes by secreting senescence-associated secretory proteins. Many studies have used mesenchymal stem cells (MSCs) to treat OA, but MSC treatment remains challenging for clinical application owing to MSC quality control, engraftment, and fibrocartilage regeneration. Here, rather than relying on the direct regeneration of MSCs, we present a novel strategy to suppress OA by MSC-mediated senescent chondrocyte targeting via the paracrine activity of MSCs, thereby improving the knee microenvironment. First, to enable quality control of umbilical cord MSCs, priming MSCs by supplementing human platelet lysate (hPL) greatly enhanced MSC functions by increasing cellular glutathione levels throughout serial passaging. Intra-articular injection of primed MSCs successfully suppressed OA progression and senescent chondrocyte accumulation without direct regeneration. Indirect coculture with primed MSCs using transwell ameliorated the senescence phenotypes in OA chondrocytes, suggesting paracrine rejuvenation. Based on secretome analysis, we identified insulin-like growth factor 2 (IGF2) as a key component that induces paracrine rejuvenation by primed MSCs. The rejuvenation effects of IGF2 act through autophagy activation through the up-regulation of autophagy-related gene expression and autophagic flux. To cross-validate the effects of secreted IGF2 in vivo, knockdown of IGF2 in primed MSCs substantially abolished its therapeutic efficacy in a rabbit OA model. Collectively, these findings demonstrate that hPL supplementation enables MSC quality control by increasing MSC glutathione levels. The therapeutic mechanism of primed MSCs was secreted IGF2, which induces paracrine rejuvenation of senescent OA chondrocytes by activating autophagy.

Extracellular vesicles (EVs) are crucial for intercellular communication and affect various physiological and pathological processes. Although terrestrial EVs have been extensively studied, marine-derived EVs have yet to be explored. This study investigated the therapeutic potential of sea cucumbers, known for their regenerative and immune abilities. Sea cucumber extracellular matrix (ECM)-anchored EVs (SEVs) were isolated and characterized using physical and electrophoretic analyses. Morphological assessments have shown that SEVs have shape and size distributions similar to mammalian EVs. Internal cargo analysis revealed the encapsulation of diverse proteins and genetic molecules. In anti-inflammatory tests with a lipopolysaccharide (LPS)-induced macrophage model, the results have shown that SEVs can alleviate inflammation factors regarding inducible nitric oxide synthase (iNOS) protein and immune-related mRNA expression. Microarray analysis was conducted to elucidate SEV's pharmacological efficacy and anti-inflammatory mechanisms, showing that SEVs inhibit the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) signaling pathway. An in vivo study using a mouse model of atopic dermatitis (AD) induced by 2,4-dinitrochlorobenzene (DNCB) involved subcutaneous SEV administration, followed by severity scoring and histological analyses. Therapeutic efficacy analysis indicated improvements in the AD mouse models, including reduced skin thickness and mast cell numbers. These findings indicate their potential for treating AD. This study highlights the potential clinical applications of marine-derived EVs and offers important implications for future research and therapeutic developments.

The Boston keratoprosthesis (BKPro) is a critical device for vision restoration in complex cases of corneal blindness, although its long-term retention is challenged by infection risks. This study aims to enhance the antimicrobial properties of the titanium (Ti) backplate of the BKPro by ion implanting silver and copper ions to achieve effective infection control while maintaining cytocompatibility. Research on antimicrobial modifications for BKPro is limited, and while metallic ions like Ag and Cu show promise for biomaterial improvement, their effects on human corneal keratocytes (HCKs) require further study. Ag and Cu were implanted onto rough Ti surfaces, as mono- and coimplantations. Cytotoxicity was assessed in HCKs, and antimicrobial efficacy was tested against Pseudomonas aeruginosa and Candida albicans. After 21 d, monoimplanted Ag samples released 300.4 ppb of Ag⁺, coimplanted samples released 427.5 ppb of Ag⁺ and 272.3 ppb of Cu ions, and monoimplanted Cu samples released 567.0 ppb of Cu ions. All ion-implanted surfaces supported HCK proliferation, exhibited no cytotoxicity, and showed strong antimicrobial activity. Ag-implanted surfaces provided antibacterial effects through membrane disruption and reactive oxygen species generation, while Cu-implanted surfaces exhibited antifungal effects via impaired enzymatic functions and reactive oxygen species. Coimplanted AgCu surfaces demonstrated synergistic antimicrobial effects, resulting from the synergy between the bactericidal actions of Ag and the oxidative stress contributions of Cu. Additionally, ion-implanted surfaces enhanced HCK adhesion under co-culture conditions. In conclusion, ion implantation effectively imparts antimicrobial properties to the Ti backplate of BKPro, reducing infection risks while preserving compatibility with corneal cells.