Regenerative Biomaterials最新文献

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.

Decellularized extracellular matrix (dECM), a promising tissue engineering scaffold for cardiovascular applications, might exhibit enhanced durability when endowed with anticalcification and antithrombotic properties. Herein, we present a biomimetic bilayer hydrogel coating applied to acellular swim bladders (ASBs). First, we designed an endothelium-mimicking (HCT) hydrogel coating, comprising alternately assembled endothelial glycocalyx macromolecule hyaluronic acid, copper ions, and tannic acid. Subsequently, a hydrophilic methacrylated silk fibroin (SilMA) hydrogel was incorporated as the outer coating layer. Notably, the HCT hydrogel penetrated and anchored into the ASB matrix, forming an interpenetrating network that enhanced the biostability and mechanical properties of the ASB matrix. Additionally, the SilMA hydrogel enhanced the hydrophilicity and antifouling properties of the HCT coating. In vitro experiments and subcutaneous implantation further revealed that the bilayer hydrogel (H/S) coating exhibited excellent biocompatibility, hemocompatibility, antibacterial activity, and anticalcification properties. Furthermore, a blood circulation model and rabbit shunt assay confirmed the great anticoagulation properties of the H/S coating. Moreover, in an in vivo rat carotid aorta replacement model, the H/S coating effectively promoted endothelialization, enhanced vascular remodeling, prevented calcification and thrombosis, and ultimately improved ASB durability. Based on these findings, our endothelium-mimicking hydrophilic bilayer hydrogel coating holds great promise as a surface modification strategy for tissue engineering scaffolds.

The human eye, a mechanically dynamic and physiologically vital organ, sustains continuous mechanical activity through repetitive blinking-averaging approximately 20 000 cycles daily, while exhibiting exceptional lubrication performance characterized by an ultralow coefficient of friction (<0.01). This remarkable lubricating functionality is mediated by the tear film, a multifunctional biological lubricant combining boundary lubrication mechanisms (via adsorbed mucins and lipids) and fluid film lubrication mechanisms to minimize friction and wear, and preserve ocular surface integrity. Failure of such ocular lubrication can cause tear film instability or ocular surface damage, leading to discomfort, visual dysfunction and dry eye syndrome. Ocular lubrication involves multiple structures and lubricants with highly complex biomolecular interactions. Insights into the structure of eyes, lubricant composition and causes of functional impairments are essential for addressing friction-related diseases in biological systems. This review examines ocular lubrication by first exploring the biological structure of the eyes and typical lubrication modes. Then, the characterization tools, such as tribometer, atomic force microscope and surface force balance in the field of ocular lubrication, are introduced, followed by a comparison of their working principles, applicable conditions and application fields. Finally, the specific causes of dry eye syndrome are outlined, along with current bio-lubricants, contact lenses and other ocular-inspired bio-lubricating materials.

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.

The great saphenous vein (GSV) is widely used in vascular surgery, especially for coronary artery bypass grafting (CABG). However, surgical injury and arterial (high) cyclic stretch induce vascular dysfunction in vein grafts. Here, we found that surgical injury induces vascular dysfunctions. Upon adhering to injured vessels, platelets release platelet-derived microvesicles, which serve as potent and persistent mediators of vascular dysfunction. RNA sequencing analysis revealed that zinc ion deficiency plays a vital role in vascular dysfunction. Of note, platelet membrane cloaked Zn-MOF nanoparticles (ZIF-8) alleviate injury-induced vascular dysfunction. To counteract the vascular dysfunction caused by surgical injury and high cyclic stretch in vein grafts, we developed an electrospun polycaprolactone (PCL) external stent loaded with zinc oxide (ZnO) (PCL-ZnO stent). Electrospun PCL external stents containing varying ZnO concentrations (0 wt%, 1 wt%, 3 wt% or 5 wt% ZnO) were fabricated and implanted around vein grafts. Vascular remodeling was assessed by histology, immunofluorescence and RNA sequencing. Moderate ZnO loading (3 wt%) suppressed neointimal hyperplasia to preserve appropriate venous arterialization as confirmed by hematoxylin and eosin (H&E) staining and increased expression of smooth muscle cell phenotypic markers including α-SMA and Calponin. RNA-seq data verified that Zn²⁺ mediates the regulation of genes involved in proliferation, inflammation and metabolism. Gene set enrichment analysis of RNA-seq data from PCL-3 wt% ZnO-treated vein grafts at 2 weeks revealed significant upregulation of gene sets associated with lipid biosynthesis and cholesterol homeostasis. Pathway enrichment analysis of differential metabolites identified significant perturbations in purine metabolism, amino sugar/nucleotide sugar metabolism, galactose metabolism, and glycerophospholipid metabolism. These results indicated that moderate ZnO incorporation (3 wt%) in external stents effectively modulated local biological responses by suppressing pathological cell proliferation without inducing apoptosis, thereby promoting proper venous arterialization. PCL-3 wt% ZnO stent may be a successful material for clinical use in alleviating intimal hyperplasia and promoting functional arterialization of grafted veins.

As the principal constituent of the extracellular matrix, collagen exhibits significant therapeutic potential in sports medicine, owing to its distinct triple-helical configuration and inherent biocompatibility. This biomaterial serves as a foundational material for scaffolds, membranes, patches and dressings targeting tendon repair, cartilage reconstruction and bone defect remediation. However, its clinical translation was hampered by limitations: poor tensile strength risks mechanical failure under load, immunogenicity from residual epitopes can trigger adverse reactions and rapid enzymatic degradation compromises structural integrity before tissue maturation. This review elucidates current properties and resources of collagen-based biomaterial and critically analyzes its inherent limitations and their clinical consequences. It emphasizes how evolving tissue engineering strategies directly mitigate barriers. Molecular crosslinking and chemical modification are employed to enhance tensile properties and delay degradation, critical for mechanically demanding environments. Composite blending with polymers compensates for mechanical weakness while retaining bioactivity. Advanced processing techniques such as 3D printing and electrospinning enable precise fiber alignment, replicating native tissue anisotropy and improving functional outcomes. Rigorous decellularization protocols further mitigate immunogenicity. This review further examines recent preclinical and clinical progress in collagen-based biomaterials for tendon, ligament, cartilage and bone regeneration, highlighting successful translations and ongoing challenges. Future directions focus on refining these strategies to accelerate the development of next-generation, clinically robust collagen therapies for sports medicine.

Severe peripheral nerve injuries represent a significant clinical problem, and intense efforts are dedicated toward the identification of the 'ideal' nerve conduit (NC). In this context, incorporating electrical cues within the device wall seems to be extremely appealing. Here, a new NC based on the new polymer oxidized polyvinyl alcohol (OxPVA) (oxidation degree 1%) + water-soluble multiwalled carbon nanotubes (MWCNT-S) (0.1 wt% in OxPVA) was developed and characterized for ultrastructure and mechanical behavior. Subsequently, OxPVA+MWCNT-S NCs were implanted in animal model of disease (Sprague-Dawley rat; sciatic nerve, gap: 5 mm) and compared with OxPVA and Reverse Autograft. Following sciatic functional index evaluation, implants-associated outcomes were verified on explants through histology, immunohistochemistry, immunofluorescence and morphometric studies on semithin sections, after 6 weeks from surgery. According to preclinical study evidence, all the NCs supported nerve regeneration (S100/β-tubulin/neurofilaments) without severe inflammatory reaction (CD3/F4/80). Morphometric studies showed the highest cross-section area and fascicular area for Reverse Autograft followed by OxPVA+MWCNT-S and OxPVA. The epineurium thickness was the highest in Reverse Autograft followed by OxPVA and OxPVA+MWCNT-S. Myelinated axon density was highest for OxPVA+MWCNT-S, followed by OxPVA and Reverse Autograft; myelinated axons total number followed this descending order Reverse Autograft˃OxPVA+MWCNT-S˃OxPVA. Additionally, the g-ratio distribution highlighted a similar trend for OxPVA+MWCNT-S and Reverse Autograft with most nerve fibers within the 0.6-0.7 interval. Atrophy of the operated-limb gastrocnemius was comparable in the whole cohort. Interestingly, MWCNT-S incorporation in OxPVA showed to be an appealing strategy to improve the morpho-structural outcomes associated with these devices.

The bacterial oral environment poses a significant challenge to the long-term stability of dental implants due to vulnerability of peri-implant soft tissues to pathogenic infiltration. Therefore, the rapid formation of a dense soft tissue barrier in the transgingival mucosal area surrounding the implant is essential. In this study, we engineer a biofunctionalized titanium (Ti) material by leveraging polydopamine (PD) as an intermediate coating to immobilize the peptide LL-37 onto nanostructured Ti substrates (LL-37-PD@NT). Material characterization shows that LL-37 is successfully loaded onto Ti substrate, and although the roughness of LL-37-PD@NT increases within a certain extent, the overall biological activity is still better than that of smooth Ti, which is considered to be traditional abutment material; meanwhile, LL-37 can be released stably for more than 1 week. Furthermore, the in vitro experiments demonstrate dual functionality of LL-37-PD@NT: the modified Ti samples significantly promote the migration, adhesion, proliferation and ECM synthesis of human gingival fibroblasts (hGFs), while exhibiting potent antibacterial efficacy against Pg and Sm. In a rat model of implantation immediately after tooth extraction, a peri-implant epithelial structure resembling the junctional epithelium of natural teeth is observed surrounding dental implant of LL-37-PD@NT at 4 weeks, and the prevention for HRP penetration exhibits the potent sealing capacity of peri-implant soft tissues. Collectively, our findings validate that the LL-37-biofunctionalized Ti can simultaneously enhance hGFs' biological functions and bacteriostatic performance, thus promoting formation and strength of soft tissue seal, holding promise as a novel option for implant abutment material.

Osteochondral defects are a challenge in orthopaedic surgery due to the complexity and function of cartilage. Within this scenario, this study aimed to develop/characterize bioactive porous supports based on oxidized polyvinyl alcohol (OxPVA), with/without human cartilage-derived decellularized ECM (dECM), as platforms for HM1-SV40 cell adhesion and proliferation. OxPVA scaffolds were fabricated using a particle-leaching technique (gelatin concentrations: 10%, 15% and 25% w/w); Scanning Electron Microscopy (SEM) was used to examine the ultrastructure, and a morphometric study assessed pores number, size and porosity percentage. Fluorescence Recovery after Photobleaching (FRAP) was used to evaluate the interconnectivity of the scaffold pores. To enhance the bioactivity of OxPVA, dECM (25% w/w) was incorporated into the scaffolds; thus, the expression of genes related to collagen synthesis and cartilage differentiation/remodelling in seeded HM1-SV40 cells was analyzed by quantitative PCR; relative protein expression levels of SOX9, ACAN and COMP were also assessed. Composite scaffolds biocompatibility was proved by subcutaneous implantation in Sprague-Dawley. As for bone, 3D-printed polylactic acid (PLA)-based scaffolds with varying geometries (67%, 53% and 40% porosity; 600-1400 µm pores size) were fabricated and tested in vitro. Lower gelatin concentrations led to numerous superficial pores, whereas higher concentrations produced larger, coalescing ones. HM1-SV40 cells showed better adhesion to scaffolds prepared with 25% gelatin. The OxPVA+dECM scaffolds exhibited a homogeneous matrix distribution, further promoting cell interaction, with a reduction in mean pore size versus matrix-free scaffolds. Moreover, OxPVA supports prepared with 25% gelatin + dECM provided a favorable environment supporting chondrogenic differentiation and cartilage matrix deposition. No inflammatory response to the implants was observed in vivo. All PLA supports showed good cell viability; SEM higlighted full-thickness HM1-SV40 cell distribution on and within PLA scaffolds, indicating complete colonization. Further studies are needed to evaluate stem cell differentiation, but bioactive OxPVA and 3D-printed PLA scaffolds show potential for osteochondral regeneration.

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.