Materials Science & Engineering C-Materials for Biological Applications最新文献

With the development of pharmaceuticals, the death rate due to cancer continues to decrease. However, the incidence of major cancers remains high. Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent type of non-skin cancers and it predominantly expresses human epidermal growth factor receptor 1 (HER1). To selectively eliminate HNSCC, cetuximab was developed as a HER1 targeting monoclonal antibody (mAb) therapy. Despite approval from the US-FDA, Cetuximab- or other anticancer drugs-related complications, such as mucosal inflammation, rash, intracranial infections, and neurological deficits, have been reported. In order to address these limitations, we have developed an antibody-drug conjugates (ADCs)-like anticancer platform called dual-targeting anticancer therapeutics (DTAT), which consists of a positioning site for mAbs or single-chain fragment variable (scFv) targeting specific antigens and a cell-penetrant cytotoxic payload targeting an oncoprotein CP2c conjugated to a cleavable linker sequence (CLS), which is sensed and cleaved by matrix metalloproteinase-11 (MMP-11). Based on this DTAT platform, we generated DTAT-D351, which dual-targets HER1 and CP2c, as an anticancer biopharmaceutical for HNSCC. Our data showed that DTAT-D351 exhibited high productivity and a strong binding affinity for HER1. Moreover, DTAT-D351 showed high anticancer potency against HER1-overexpressing cancer cells and A431 epidermoid squamous carcinoma cells. Moreover, it showed no adverse reactions in immune cells and normal cells. In conclusion, DTAT-D351, herein called Cetuximab scFv-CPTin, is a promising and effective anticancer agent for the treatment of HER1-overexpressing cancer cells, including head and neck cancers.

Stress urine incontinence (SUI) affects women's physical, mental, and social health. The minimally invasive periurethral injection of hyaluronic acid-based hydrogels has gained popularity for urethral support and continence. SUI therapy is tried using novel hyaluronic acid-based hydrogels loaded with ginsenoside Rb1 (HB-Rb1). It has good biocompatibility, mechanical strength, and swelling ratio. The hydrogel's cytocompatibility and good cellular adhesion in L929 cells suggested it could reduce inflammation and assist tissue regeneration. In mice with SUI, HB-Rb1 improved the local microenvironment, collagen deposition, and urethral tissue regeneration, relieving SUI symptoms. H&E staining assessed histological alterations. The results demonstrate that HB-Rb1 can treat SUI and that nursing care is essential. Long-term efficacy and clinical translation of advanced biomaterials and nursing-led care in women's health should be the focus of future study.

The antitumor immune response induced by nuclear DNA damage from radiotherapy is emerging as a promising strategy, with cGAS accumulation in micronuclei triggering intracellular inflammatory pathways. However, radiotherapy-induced DNA damage also activates the DNA damage response (DDR), which suppresses antitumor inflammation. To address this, we developed an innovative "particle capsule" nanosystem that amplifies DNA damage while inhibiting the DDR. Magnetite nanoparticles (Fe₃O₄ NPs) are "devoured" by bacteria through ABC transporter channels and then packaged with the ATR inhibitor VE822 inside OMVs engineered with iRGD tumor-homing peptides. This design enables efficient penetration across tumor tissue and the blood-brain barrier, facilitating deep tumor delivery. The system leverages the synergistic effects of Fe₃O₄-driven Fenton reactions for enhanced hydroxyl radical (•OH) production and ATR inhibition for DNA repair blockade, resulting in sustained DNA damage and DDR suppression. In addition, the intrinsic immunostimulatory properties of OMVs activate innate immune pathways, synergistically boosting antitumor immunity. Consequently, this strategy reduces tumor radioresistance, reactivates DNA damage-induced inflammation, promotes effector T cell infiltration, and overcomes challenges posed by irregular tumor vasculature and poor lymphatic drainage, ultimately achieving significant tumor growth inhibition and a superior antitumor immune response in mice.

Chronic wounds, characterized by persistent inflammation, impaired angiogenesis, and disrupted tissue regeneration, remain a major clinical challenge. Current therapies can alleviate symptoms but fail to achieve long-term regulation of the wound microenvironment and functional regeneration. To overcome these limitations, a self-healing collagen-oxidized hyaluronic acid hydrogel loaded with platelet-rich plasma (COL-OHA@PRP) based on dynamic covalent crosslinking was developed, integrating two clinically applied therapies-collagen (COL) and platelet-rich plasma (PRP)-into a single platform. Guided by the design concept of "sustained release-protection-synergy", this hydrogel integrates three essential functions: self-healing ability, tissue adhesiveness, and controlled PRP release. While preserving the native triple-helix structure of COL, the hydrogel forms a stable adhesive interface with the wound surface, enabling sustained release and protection of bioactive factors in PRP, and synergistically regulating inflammation and tissue regeneration. In vivo studies demonstrated that COL-OHA@PRP hydrogel continuously released multiple bioactive factors, effectively attenuated inflammation and oxidative stress, promoted angiogenesis and COL remodeling, and accelerated wound closure and re-epithelialization. This hydrogel demonstrated sustained therapeutic efficacy following a single administration in a diabetic wound animal model, highlighting its potential as a promising biomaterial platform for further translational investigation in chronic wound treatment.

Persistent inflammatory response and impaired angiogenesis both contribute to delayed diabetic wound healing. Combined counteracting inflammation and facilitating angiogenesis showed considerable potential in diabetic wound management. Herein, a natural collagen-based thermosensitive hydrogel encapsulated with costunolide and copper ions was constructed. The collagen was cross-linked with EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide)/NHS (N-hydroxysuccinimide) and soaked with ammonium sulfate to augment its mechanical strength. The composite hydrogel demonstrated a thermosensitive release of costunolide and copper ions (in response to physiological temperature), coupled with remarkable biocompatibility. The hydrogel system significantly promoted the proliferation of fibroblasts and endothelial cells and concurrently enhanced the migration of endothelial cells in vitro. Meanwhile, the composite hydrogel exerted an anti-inflammatory effect by reducing the expression of pro-inflammatory cytokines in lipopolysaccharide (LPS)-activated macrophages. Moreover, treatment with the multifunctional hydrogel resulted in an improved inflammatory microenvironment and enhanced angiogenesis, which subsequently promoted cell proliferation, collagen deposition and re-epithelialization, and ultimately accelerated wound healing in a diabetic rat model. In conclusion, the natural collagen-based thermosensitive multifunctional hydrogel, as an advanced wound dressing, offers a novel therapeutic delivery strategy for the treatment of diabetic wounds.

Myocardial infarction (MI) is one of the primary predisposing factors for heart failure and poses a significant threat to human health. Concurrently, the vascular architecture of the heart is compromised, and its inherent repair capacity is notably limited. Vascular endothelial growth factor (VEGF)-based pro-angiogenic therapies have shown promising efficacy. Nevertheless, their direct application is still plagued by substantial limitations regarding therapeutic efficacy. Herein, we have designed HANB/F127DA hydrogel patch has been developed for VEGF delivery. This hydrogel enables the sustained and gradual release of VEGF without impairing its activity, while also possessing tunable mechanical properties and tissue adhesion capabilities. In vitro experiments have demonstrated that VEGF is rapidly released initially, followed by a sustained release phase, thereby promoting early angiogenesis and preventing its regression. The administration of VEGF-loaded HANB/F127DA hydrogel onto the MI site in Sprague-Dawley rats has been shown to effectively stimulate neovascularization, attenuate inflammatory responses, reduce fibrosis, and enhance cardiac function. Moreover, exercise training has been shown to improve blood circulation and stimulate angiogenesis. Consequently, the concurrent application of exercise training may exert a synergistic effect. The findings of the study suggest that the combined application of HANB/F127DA@VEGF hydrogel and a 4-week exercise regimen can significantly enhance neovascularization and improve cardiac function in rats with MI.

Blood-contacting medical devices are susceptible to thrombosis, infection, and impaired endothelialization, complications that are often managed pharmacologically, despite the risk of systemic side effects. As an alternative, surface modification provides a localized strategy to improve hemocompatibility and reduce complications at the blood-material interface. Heparinized surfaces have been used for several decades in blood-contacting applications because heparinization mimics the lining of blood vessels and imparts multiple biochemical functions that improve blood compatibility. However, animal-derived heparin products have multiple challenges that motivate the search for alternatives. In this study, we developed multifunctional polyelectrolyte multilayer surfaces (PEMs) utilizing the polycation Tanfloc (TAN) combined with heparin and candidate plant-derived and animal-derived alternatives: carboxymethyl-kappa-carrageenan (CMKC), kappa-carrageenan (KC), or hyaluronic acid (HA), deposited on titania nanotube (TiNT) surfaces. We extensively characterized CMKC, a chemically modified polysaccharide that integrates both sulfate and carboxyl functional groups, aiming to replicate and potentially surpass the anticoagulant and antimicrobial performance of heparin-based coatings. TAN-CMKC coatings demonstrated exceptional biological outcomes, including significantly reduced fibrinogen adsorption, minimized platelet and leukocyte adhesion, and superior resistance against bacterial colonization by clinically relevant strains, Staphylococcus aureus and Pseudomonas aeruginosa. Furthermore, these multilayers markedly accelerated endothelial cell adhesion, proliferation, and migration, simultaneously suppressing smooth muscle cell (SMC) proliferation and phenotypic modulation. Comparative analyses revealed that CMKC's combined sulfate and carboxyl functionalities substantially enhanced hemocompatibility, endothelialization, and antimicrobial efficacy relative to coatings containing exclusively sulfate (KC), carboxyl (HA), or animal-derived heparin. This work substantiates TAN-CMKC PEMs as a potent, sustainable biomaterial strategy for advanced cardiovascular device coatings.

Cancer stem cells (CSCs) have been implicated as potential contributors to tumor recurrence, therapeutic resistance, and metastatic behavior. While traditional 3D spheroid models have advanced CSC research, their multilayered architecture introduces cellular heterogeneity and limits reproducibility. Here, we present a 3D microbead-based culture platform that enables spatially uniform induction of CSC-like phenotypes in cancer cells and scalable expansion of malignancy-enriched cells. By leveraging omnidirectional curvature cues provided from suspended microbeads, we achieved enhanced mechanotransductive stimulation across the entire ovarian cancer cell surface. To guide preferential adhesion to the beads and minimize nonspecific substrate attachment, we employed initiated chemical vapor deposition (iCVD) to coat the bottom surface with hydrophobic polymers, where poly(cyclohexyl methacrylate) (pCHMA) promoted microbead-specific adhesion effectively. Cancer cells cultured on this microbead-based system exhibited upregulation of the genes associated with tumor aggressiveness and invasive phenotypes exceeding those observed in conventional 2D monolayer and 3D spheroid models. Mechanistically, these effects were closely associated with curvature-induced RhoA signaling and cytoskeletal remodeling. Furthermore, this platform supported large-scale, high-throughput-compatible expansion of aggressive cancer cells, offering a robust tool for CSC-focused studies and drug screening. Our findings highlight the utility of curvature-mediated mechanobiology in engineering more physiologically relevant and scalable in vitro cancer models.