Hydrogels are 3D crosslinked polymeric networks that can absorb and retain substantial quantities of water or biological fluids. Their soft, hydrated nature and adjustable properties render them highly suitable for a range of biomedical applications, such as drug delivery, tissue engineering and wound healing, by emulating the extracellular matrix. To overcome the limitations associated with the mechanical properties and biological functions of conventional elastin-like polypeptide (ELP) and sodium alginate (SA) hydrogels, a novel ion-responsive two-component ELP-SA hydrogel was developed. ELP variants with functional modules (ELPK/ELPR/ELPS/ELPL) were engineered through genetic techniques and purified to a high degree of purity (>95%) using high-salt-reversible phase-change technology. The release of Ca2+ from gluconolactone simultaneously initiated ELP self-assembly and SA ion crosslinking, resulting in the formation of an injectable composite gel within 10 min. This material demonstrated enhanced mechanical properties (storage modulus G′ 450–1773 Pa, pore size 52–103 μm) and reduced swelling (decreased to 60% of that of the SA hydrogel). Functionally, ELPR improved cell adhesion (1.42 times that of collagen I), ELPS facilitated angiogenesis (1.32 times higher than that of the positive control), and ELPL achieved an antibacterial rate exceeding 98% and induced macrophage M2 polarization. This supports the growth of 3D cell spheroids (survival rate of >95%). This modular design synergistically integrates mechanical strength with diverse biological activities, providing an intelligent dressing solution with antibacterial, healing, and anti-inflammatory properties for treating chronic wounds.

One of the most prevalent malignant tumors in women is cervical cancer. Conventional chemoradiotherapy was frequently limited by significant side effects and acquired drug resistance. Consequently, there is an urgent need for high-performance biomaterials that effectively suppress tumor growth while exhibiting minimal off-target toxicity. Magnesium alloys represented a promising platform for anti-tumor applications due to their bioactive degradation products. This study developed novel magnesium alloy-mineralized collagen composite scaffolds and systematically evaluated their surface properties. Comprehensive in vitro and in vivo experimental models were used to elucidate the scaffolds’ anti-tumor mechanisms. The results of this study demonstrated that magnesium alloy-mineralized collagen composite scaffolds significantly inhibit tumor cell invasion and metastasis while promoting cancer cell death. Based on in vivo and in vitro studies, this study showed that the degradation products of magnesium alloy-mineralized collagen composite scaffolds target epithelial–mesenchymal transition through the Wnt/β-catenin/TCF7 signaling pathway. These findings established a robust experimental foundation for advancing magnesium alloy-mineralized collagen composite scaffolds as next-generation biodegradable adjunctive therapeutic materials for cervical cancer treatment. The synergistic combination of biocompatibility and tumor-targeted activity positions this material as an innovative platform for circumventing shortcomings in existing clinical regimens.

We previously described the production of hydrophilic hydrogel scaffolds of cross-linked chitosan that closely matched the biomechanical properties of native human tarsus. In the present preclinical study we appraised the spatio-temporal tissue response to the implantation of these chitosan scaffolds into rat eyelids. Acellular hydrogel scaffolds were produced from Good Manufacturing Practice (GMP)-compliant chitosan and implanted into rat eyelids. Tissue was harvested and fixed up to 24 weeks post-surgery for histological examination of the tissue response to both the surgical procedure itself and to the chitosan implantation. Assessment encompassed inflammation, the foreign body reaction (FBR) and infiltration of native cells into the implant region, along with scaffold degradation. Three days after implantation of the chitosan into rat eyelids, neutrophils were observed in the vicinity of the chitosan but their prevalence declined rapidly thereafter. Both pro-inflammatory M1-macrophages and anti-inflammatory M2-macrophages were also observed post-implantation at the scaffold-tissue interface but the former cells declined after 4 weeks. Unlike the M1-macrophages, the M2-macrophages rarely infiltrated the scaffold at any time point. T cells and MHC class II antigen-presenting cells were predominantly increased at the tissue-scaffold interface and, to a minor degree, within the scaffold, in the weeks following surgery. In the weeks following implantation, a fibro-collagenous capsule gradually formed at the margins of the scaffolds, denoting the classic FBR. This was accompanied by the appearance of foreign body giant cells, moderate to substantial degradation and engulfment of chitosan by infiltrating cells, and localized tissue remodelling characterized by proliferation of fibroblasts, deposition of collagenous extracellular matrix (ECM) material and rudimentary formation of vascular elements within the scaffold. Although the chitosan scaffolds initially elicited widespread inflammation and an FBR, longer-term tissue remodelling and scaffold degradation suggested their biocompatibility. These data support that chitosan hydrogel scaffolds could, therefore, serve as suitable tarsal substitute material in situ.

Titanium-based materials are commonly utilized in bone tissue repair due to their exceptional physical and chemical properties. Surface modification of titanium dioxide (TiO2) nanotubes effectively modulates cellular osteo-adipogenic balance, thereby promoting stem cells osteogenic differentiation. Sterol regulatory element-binding protein 1 (SREBP1), a pivotal transcriptional factor involved in lipid metabolism, plays a significant role in mechanotransduction. Nevertheless, it remains unclear whether SREBP1 also exerts a crucial influence on regulating the differentiation of bone marrow mesenchymal stem cells induced by TiO2 nanotubes and its involvement in mechanotransduction during this process. Therefore, this study aimed to investigate the mechanistic role of SREBP1 in cell differentiation induced by TiO2 nanotubes. The results demonstrated that TiO2 nanotubes exerted regulatory control over SREBP1, enhancing the expression of regulatory factors that induce osteogenic differentiation while suppressing the expression of marker genes associated with adipogenic differentiation. Simultaneously, this regulation inhibited the transcription and translation of pivotal enzymes involved in fatty acid anabolism. Activated by the nanostructure, Lipin1 acted as an upstream target that negatively regulated the expression of SREBP1. The signaling pathway involving Lipin1/SREBP1 was regulated by stress fibers responding to mechanotransduction induced by TiO2 nanotubes. Consequently, SREBP1 serves as a critical regulatory factor linking mechanotransduction mediated by TiO2 nanotubes and maintaining homeostasis between stem cell osteo-adipogenic differentiation processes. This provides novel insights for designing biomaterials for bone repair.

A variety of novel peptide-grafted hydrogels, of which peptides were derived from vitronectin (PQVTRGDVFTMP) or the laminin β4 chain (PMQKMRGDVFSP), were prepared in this study. The peptide-grafted hydrogels promoted the adhesion, proliferation and colony formation of hiPSCs and maintained their pluripotency up to passage 5 under xeno-free conditions. We successfully generated RPE cells from hiPSCs using one of the most suitable xeno-free peptide-grafted hydrogels, KVN2CK (KGCGGKGG-PQVTRGDVFTMP), which was derived from vitronectin, and confirmed the effect of these hiPSC-derived RPE cells in a rat retinal degeneration model (Royal College of Surgeons (RCS) rats) via subretinal transplantation, when we investigated functional improvements in vision in RCS rats after the transplantation of hiPSC-derived RPE cells. Our novel peptide-grafted hydrogels provided a safe and robust platform for generating single-layer hiPSC-derived RPE cells under xeno-free conditions, which indicates the potential of these hydrogels for stem cell therapy for retinal degenerative diseases in the future.

Cholestatic liver disease (CLD) is characterized by disruptions in bile formation, secretion and excretion, leading to progressive liver injury, inflammation and fibrosis. Effective treatments to halt or reverse the progression of CLD remain limited. The Wnt/β-catenin signaling pathway has been implicated in the regulation of bile acid homeostasis and liver regeneration, playing a complex role in CLD pathophysiology. Tetrahedral framework nucleic acids (TFNAs), a class of anti-inflammatory and antioxidant DNA nanomaterials, have shown potential in promoting mammalian cell proliferation through activation of cell cycle and proliferation-related signaling pathways. However, their therapeutic potential in CLD has not been fully explored. In this study, we investigated the effects of TFNAs in an α-naphthyl isothiocyanate (ANIT)-induced mouse model of CLD. TFNAs demonstrated the ability to enter hepatocytes, where they activated the Wnt/β-catenin signaling pathway and enhanced ERK1/2 phosphorylation. These molecular changes resulted in significant improvements in liver injury markers, bile acid metabolism and liver regeneration. Complementary in vitro experiments revealed that TFNAs reduced hepatocyte apoptosis and oxidative stress, while promoting cell viability and proliferation. Histological analysis confirmed that TFNAs treatment mitigated liver necrosis, reduced ductular reactions and decreased neutrophil infiltration, highlighting their anti-inflammatory and tissue-protective effects. These findings provide compelling evidence that TFNAs can ameliorate CLD by modulating key signaling pathways involved in hepatocyte survival, regeneration and bile acid homeostasis. Collectively, our findings highlight the therapeutic potential of TFNAs as a novel treatment for CLD and paves the way for further exploration of nanomaterials in liver disease therapy.

Poloxamer 407, also known as Pluronic® F127, is gaining interest in the cosmetic, biomedical and pharmaceutical fields for its biocompatibility, safety and thermo-sensitive properties. Ensuring sterility is critical in clinical applications, and sterilization is often preferred over aseptic processing. However, sterilization can impact the functional properties of the hydrogel. In this study, we investigate the effects of steam heat (121°C, 20 min), dry heat (160°C, 1 h), gamma irradiation (25 kGy) and electron beam (e-beam) irradiation (15 and 25 kGy) on a 30% w/v Poloxamer 407 hydrogel formulation. Our analysis encompasses gelling properties, pH, Fourier-transform infrared spectroscopy, gel permeation chromatography, small-angle X-ray scattering, rheology, swelling, degradation by-products and lactate dehydrogenase release of the sterilized hydrogels, comparing them to a non-sterile counterpart. We demonstrated that heat sterilization alters the hydrogel's gelling and structural properties due to water evaporation and oxidation under harsh temperature conditions, especially when applying the dry heat method. Gamma irradiation proved unsuitable, resulting in an acidic and cytotoxic hydrogel due to oxidative degradation. In contrast, e-beam irradiation preserves the hydrogel's elasticity, gelling and structural properties while enhancing mechanical resilience and moderating swelling. Therefore, e-beam irradiation within the 15-25 kGy range appears to be the most suitable method for sterilizing a 30% w/v Poloxamer 407 hydrogel.

Reconstructing bone defects remains a significant challenge in clinical practice, driving the urgent need for advanced artificial grafts that simultaneously promote vascularization and osteogenesis. Addressing the critical trade-off between achieving high porosity/strength and effective bioactivity at safe ion doses, we incorporated strontium (Sr) into β-tricalcium phosphate (β-TCP) scaffolds with a triply periodic minimal surface (TPMS) structure using digital light processing (DLP)-based three-dimensional (3D) printing. Systematically screening Sr concentrations (0–10 mol%), we identified 10 mol% as optimal, leveraging the synergy between the biomimetic TPMS architecture, providing exceptional mechanical strength (up to 1.44 MPa at 80% porosity) and facilitating cell recruitment and precision Sr-dosing to enhance bioactivity. In vitro assays revealed that the Sr-TCP scaffold dose-dependently stimulated osteogenic differentiation and mineralization in mouse osteoblastic cell line (MC3T3-E1) cells, while also significantly enhancing the angiogenic capacity in human umbilical vein endothelial cells (HUVECs). In vivo studies indicated that the scaffold demonstrated synergistic osteogenic and angiogenic effects in rat femoral condylar defects, leading to marked improvements in bone healing. Collectively, this study establishes a novel design paradigm combining biomimetic topology with optimized ionic doping, resolving key limitations of conventional grafts and advancing the development of safe, highly effective biomaterials for vascularized bone regeneration.

Developing mechanical adaptable injectable gel with nucleus pulposus (NP) repairing capability for minimally invasive treatment of intervertebral disc degeneration (IDD) is of great importance in medical practice. In current work, inspired by the outcomes of polyvinyl alcohol and glycerol based injectable organohydrogel (GPG) in IDD control and the great potential of animal glue in tissue adhesion, a novel injectable and self-crosslinking adhesive organohydrogel GPG-AG was fabricated. The mechanical performance of the GPG-AG was systematically studied, possessing viscoelastic properties close to NP accompanied with strong adhesion to intervertebral disc to avoid dynamic loading induced leakage postinjection. In addition, the swelling behavior, water retention capability and degradation of the organohydrogel in situ was also explored. In vitro cellular test showed the as-fabricated organohydrogel was able to upgrade aggrecan expression while downregulate matrix metallopeptidase-13 (MMP-13) synthesis. Astoundingly, the organohydrogel revealed anti-inflammation potential of alleviating excessive reactive oxygen species, consequently creating a favored microenvironment for NP repairing. The corresponding in vivo study showed the outcome in intervertebral disc height index of the GPG-AG treated group after needle puncture was superior to previously reported GPG and control group. Taken together, this organohydrogel is expected to serve as a promising candidate for IDD control.

Mandibular radiation-induced bone injury (RIBI) is a common, severe complication of radiotherapy with no effective treatment. The early course is clinically subtle yet pathologically complex: ionizing radiation (IR) rapidly induces microvascular dysfunction, amplifies immune-mediated inflammation and disrupts bone homeostasis. This complexity, together with safety considerations, hampers therapeutic translation. Magnesium (Mg2+) is an essential bone component whose pro-osteogenic activity is well established; nevertheless, irradiation may remodel the multi-target effects of bioactive ions, and the integrated mechanisms of Mg2+ in bone radiation injury remain to be clarified. Here, we compared local delivery of an Mg2+- crosslinked alginate hydrogel (Mg@Alg) under irradiated versus non-irradiated conditions in rats and combined macrophage and endothelial cell models to evaluate radioprotective effects and mechanisms. In our study, Mg@Alg attenuated bone loss and apoptosis within 14 days after IR, promoted M2-like macrophage polarization, and improved microvascular density and maturation, thereby contributing to inflammatory microenvironment remodeling. Mechanistically, Mg2+ intervention was accompanied by decreased ferritin, downregulation of prolyl hydroxylase domain-2 (PHD2), and stabilization of hypoxia-inducible factor-1α (HIF-1α), together with vascular endothelial growth factor A upregulation; these changes were partly reversed by Fe2+, suggesting an iron-dependent, PHD2/HIF-1α-biased modulation that coordinates immune homeostasis and vascular regeneration to improve immune–vascular coupling. Notably, while Mg2+ efficacy appeared enhanced under IR, the effective concentration window narrowed. In sum, peri-radiotherapy, localized, short-term Mg2+ delivery may improve bone tolerance to radiation and mitigate early RIBI. These findings provide an experimental basis for low-risk, clinically translatable bone radioprotective strategies and expand the application paradigm of magnesium-based materials in radiotherapy protection contexts.