Acta biomaterialia最新文献

Emergency corneal injuries necessitate immediate intervention to minimize the risk of infection and maintain optical clarity. However, corneal transplantation is unsuitable due to donor shortage and surgical complexity. Inspired by the synergistic role of collagen and glycosaminoglycans in the natural cornea extracellular matrix, a visible light-initiated, in situ dual-crosslinked hydrogel bioadhesive (GelMA-CSMA-NHS) is prepared by combining gelatin methacryloyl (GelMA) and N-hydroxysuccinimide-modified chondroitin sulfate methacrylate (CSMA-NHS). Upon exposure to 405 nm light, the bioadhesive precursor rapidly forms a hydrogel within 3 min directly on the injured cornea. It establishes strong interfacial integration with the tissue through topological entanglement and NHS-amine covalent crosslinking, thereby serving as a suture-free alternative for corneal repair. The dual-crosslinking mechanism significantly enhances the mechanical cohesion of the hydrogel, which synergistically improves its adhesive performance. The resulting hydrogel demonstrates high transparency, stable swelling behavior, good biocompatibility and biodegradability, and high burst pressure resistance. Using established models of partial stromal defects and full-thickness corneal lacerations, the bioadhesive integration and pro-healing effects of the hydrogel were evaluated. The results showed that the hydrogel bioadhesive rapidly seals corneal wounds, promotes re-epithelialization, reduces scarring formation, and supports full-thickness corneal regeneration. STATEMENT OF SIGNIFICANCE: To address the limitations of traditional surgical sutures in treating acute corneal injuries, we developed a hydrogel bioadhesive (GelMA-CSMA-NHS). Inspired by the composition of the natural corneal extracellular matrix, the adhesive is fabricated from two derivatives of natural bioactive macromolecules. It can be rapidly crosslinked in situ on the injured cornea under visible light initiation via a dual-crosslinking mechanism, forming a strong adhesive interface with the tissue through topological entanglement and NHS-amine covalent bonding. In terms of performance, the hydrogel bioadhesive exhibits high transparency, good biocompatibility and biodegradability, and high burst pressure resistance. The hydrogel was evaluated in two models of acute corneal injury-partial stromal defects and full-thickness corneal lacerations. It accelerates re-epithelialization, minimizes scarring formation, and supports full-thickness corneal regeneration. Thus, this hydrogel bioadhesive shows considerable potential for emergency corneal repair and regenerative medicine.

In the past 20 years, minimally invasive delivery strategies have emerged to bridge the therapeutic gap between highly invasive surgery and less efficient nonsurgical approaches. New, less invasive technologies, including vascular, transendocardial, thoracoscopic, and inhalation delivery methods, can enhance cardiac targeting, promote drug retention, and minimize trauma compared to conventional interventions. Understanding current therapeutic agents, including biomolecules, biomaterials, and medical devices, along with their respective mechanisms, is essential for optimizing minimally invasive delivery strategies. Despite current therapeutic promises, dynamic heart motion and low delivery efficiency hinder the clinical translation of minimally invasive heart repair. Future studies should aim to address these hurdles by optimizing cardiac uptake, advancing personalized medicine, and developing safer delivery tools. To map the state of the field and its future potential, this review summarizes several minimally invasive cardiac delivery approaches and how to leverage existing techniques in concert to harness the impact of minimally invasive cardiac delivery. STATEMENT OF SIGNIFICANCE: Minimally invasive cardiac delivery techniques represent an important advancement in treating heart diseases, bridging the gap between invasive surgeries and less effective nonsurgical methods. Unlike traditional approaches, these novel methods, including vascular, transendocardial, thoracoscopic, and inhalation techniques, provide targeted drug delivery directly to the heart while reducing trauma. This review uniquely synthesizes current advancements in delivering therapeutic agents such as biomolecules and medical devices, highlighting their improved cardiac targeting and retention capabilities. It identifies critical challenges, including the heart's motion and low delivery efficiency, and discusses opportunities for innovation. Addressing these challenges can significantly impact patient outcomes, enhance personalized treatments, and advance the broader field of minimally invasive cardiovascular medicine.

Metal-directed self-assembly, driven by metal-ligand coordination, represents a highly versatile and efficient strategy for constructing drug delivery systems with precisely tunable properties, inherent imaging capabilities, and broad biomedical applications. Stimuli-responsive metal-directed drug delivery systems (MDDSs), guided by advanced imaging techniques, enable precise control over their size and spatial architecture while facilitating site-specific drug release. Moreover, certain metal ions play a dual role, not only orchestrating the self-assembly process but also serving as therapeutic agents and regulatory components for the treatment of various diseases, including cancer, microbial infections, and Alzheimer's disease. This review provides a comprehensive overview of the self-assembly mechanisms underlying diverse MDDSs and their applications in image-guided therapy. Furthermore, we critically examine existing challenges in the field and propose strategic directions to propel the advancement of metal-directed self-assembly in drug delivery. Given the profound implications of this research, further exploration of the critical roles of metal coordination in self-assembly is imperative for the development of next-generation drug delivery platforms. STATEMENT OF SIGNIFICANCE: This review systematically summarize the self-assembly mechanisms of metal-directed drug delivery systems, outlines their applications in image-guided therapy and discusses the current challenges that remain. Furthermore, it elucidates the unique regulatory roles of metal ions in precise drug release and multimodal therapy, providing valuable insights and broad appeal for the development and clinical translation of next-generation smart nanomedicine platforms.

Controlled degradation of extracellular matrix-derived biomaterials in a site-specific and temporal sequence might facilitate early vascularization and improve tissue regeneration. In this study, we developed a tailored laser patterning treatment that successfully addresses this challenge. We show that application of a focused diode-pumped solid-state laser (532 nm) for 30 s duration leads to local heating and reduction of collagen fibril integrity in localized laser-patterned areas of a collagen biomaterial. When implanted in vivo, these thermally degraded regions then become susceptible to further in vivo degradation by inducing site-specific resorption. This allows unimpeded vascular ingrowth and accelerated recovery without prematurely compromising biomaterial structural integrity. Using peripheral nerve injury as an exemplar indication, we show that laser-treated collagen-based nerve guidance conduits (NGCs) have enhanced regenerative potential. Increased in vivo vascularization, in comparison to non laser-treated NGCs, was shown in both a chick chorioallantoic membrane and a rat critical-sized 15 mm sciatic nerve defect model. When nerve repair was assessed, laser-treated NGCs promoted aligned axonal growth and myelin sheath distribution resembling the native nerve, while also restoring nerve action potential to levels of a healthy nerve. This resulted in functional healing and successful nerve recovery as demonstrated by significantly reduced muscle atrophy. This straightforward yet innovative approach offers significant potential for enhancing functional nerve repair when utilizing collagen-based biomaterials but can also be applied to other natural polymer-based biomaterials to tailor degradation and vascularization for a myriad of indications. STATEMENT OF SIGNIFICANCE: A major challenge associated with implanted biomaterials is the limited control over biomaterial degradation, which can result in failure to adequately repair damaged tissues. In this study, we address this issue through the use of laser patterning which produces localized changes in the structure of extracellular matrix-based biomaterials in the form of depressions and changes in the biochemical composition which then accelerate in vivo biomaterial resorption as the depressions then develop into physical voids. This directs early cell infiltration and eventually vascularization into the biomaterial. At the same time, we show that site-specific resorption does not compromise overall material integrity and allows the implanted biomaterial to maintain its structure so as to facilitate new tissue formation at the injured site.

Coarctation of the aorta (COA) is a congenital heart disease for which successful intervention can restore flow and reduce the blood pressure gradient, but does not ensure long-term health. Adults with successfully treated COA exhibit significantly higher incidence of hypertension. The objective of this study was to measure differences in the structure and mechanics of proximal and distal aortic tissue from the first age-appropriate, physiologically relevant growing porcine model of COA. This animal model also enabled the evaluation of a cutting-edge serially dilatable stent. Quantitative histologic analysis measured structural changes and the mechanical properties were investigated through uniaxial, shear lap, and peel tests of tissue from sham, control COA, and treated COA animals. Our original hypothesis that proximal aortic tissue from control and treated COA groups would be thicker and have less elastin was false. There were no significant differences in elastin content, collagen content, lumen area, or lumen-to-tissue area between groups. Mechanically, distal tissue also exhibited no difference in either uniaxial or shear lap stiffness, failure stress, or failure strain between groups. Distal tissue from the COA control and treated COA groups however, exhibited, a lower circumferential failure peel tension, suggesting interlamellar strength was reduced. When compared with other previously published animal models of COA, a clear distinction was timing - our growing porcine model is the first for which COA was induced and treated at physiologically relevant time points. Our results indicated minimal adverse vascular remodeling in either the COA control or treated COA groups, however, it is unclear if this was due to a lack of severity, if elastinogenesis compensated for damage, or if another unknown mechanism prevented remodeling. STATEMENT OF SIGNIFICANCE: Coarctation of the aorta is one of the most common congenital heart diseases, yet the mechanisms behind it and its associated comorbidities remain poorly understood. To our knowledge, this was the first study to characterize tissue from a growing porcine model, with coarctation induced and treated at a physiologically relevant ages. Additionally, we investigated a new and emerging technology to treat coarctation and correlated the mechanical characterization of the aortic tissue with structural changes observed via quantitative histologic analysis.

Current challenges in biomaterials center on a fundamental conflict between bioactivity and physiological homeostasis in material design. Inorganic biomaterials such as bioceramics and bioglasses exemplify this dilemma, as the release of functional ions is often accompanied by excessive alkalinization that limits practical use. We prepared a homogeneous lithium-calcium-silicate bioactive glass (LCS-CP) through containerless processing technique. LCS-CP maintained a mild alkaline microenvironment (pH < 8.0 in cell culture; < 9.2 in Tris-HCl over 50 days) and released substantially lower amounts of Li and Si than its crystalline counterpart (LCS-C) during 14-day cell culture, consistent with a more regulated bulk dissolution behavior. Although LCS-CP and melt-quenched glass (LCS-MQ) exhibited comparable averaged ion release and pH trends, LCS-CP showed more favorable interfacial outcomes, including more continuous and mature Ca-P deposition during time-resolved mineralization, which we attribute to its more homogeneous fully amorphous structure and uniformly distributed reactive sites. Functionally, LCS-CP promoted the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and mitigated neutrophil overactivation and pro-inflammatory factor secretion in vitro. In vivo, LCS-CP reduced early-stage inflammatory responses and supported tissue repair after implantation. Overall, this work demonstrates a containerless-processing route to develop bioactive materials with improved compatibility with homeostatic regulation. STATEMENT OF SIGNIFICANCE: This work addresses a fundamental challenge in biomaterials: the conflict between bioactivity and physiological homeostasis. Lithium-calcium-silicate bioactive glass (LCS-CP) is developed using containerless processing, a technique that inhibits crystallization and creates a homogeneous, ion-rich structure. Unlike conventional materials, LCS-CP releases lithium, calcium, and silicon ions in a controlled manner to exert osteogenic and anti-inflammatory functions with a mild alkaline pH beneficial for tissue repair. It significantly enhances stem cell-based bone formation and suppresses neutrophil-driven inflammation. This study demonstrates that lithium-calcium-silicon homogeneous glass prepared by containerless processing can reconcile bioactivity with biosafety, offering a new strategy for designing adaptive biomaterials with broad significance in regenerative medicine.

Periodontitis is a pathogenic microbial-infected disease where immune dysregulation promotes chronic inflammation and excessive osteoclast activity, causing progressive tissue destruction. Current therapeutic approaches face challenges in achieving sustained drug release in periodontal pockets. In this study, we construct a self-assembled peptide hydrogel by combining negatively charged peptide amphiphile (PA) with positively charged antimicrobial peptide GL13K, namely PA/GL13K. GL13K electrostatically binds to self-assembled PA nanofibers, promoting PA self-assembly that yields a denser hydrogel network. This structural reinforcement enables sustained GL13K release. The PA/GL13K hydrogel demonstrates potent antibacterial effects and immunomodulatory properties, suppressing pro-inflammatory M1 macrophage polarization while promoting anti-inflammatory M2 macrophage activation. Moreover, the PA/GL13K hydrogel inhibits osteoclast differentiation in vitro. In an experimental periodontitis mouse model, local periodontal injection of the PA/GL13K hydrogel reduced inflammatory infiltration and osteoclast-mediated bone resorption, effectively mitigating periodontal tissue destruction. These findings suggest that the self-assembled peptide hydrogel system may represent a potential multifunctional therapeutic approach for periodontal treatment. STATEMENT OF SIGNIFICANCE: This study presents a peptide-based hydrogel system designed for the comprehensive treatment of periodontitis, addressing critical challenges in current therapeutic strategies. The self-assembled charge-complementary hydrogel is composed of negatively charged peptide amphiphile (PA) and positively charged antimicrobial peptide GL13K. GL13K electrostatically binds to self-assembled PA nanofibers, promoting PA self-assembly that yields a denser hydrogel network. This structural reinforcement enables sustained GL13K release. The system demonstrates synergistic effects, including antibacterial activity, immunomodulatory effects, and inhibition of osteoclastogenesis. Our findings highlight the hydrogel's potential as a promising platform for periodontitis management, combining structural optimization with multifunctional therapeutic outcomes.

Biomaterials mimic extracellular matrix (ECM) in tissue regeneration by providing essential physical and biochemical cues for stem cell growth; many studies have revealed the influence of such cues on stem cell fate. However, curved surfaces, the basic geometry of organisms, have rarely been considered. Besides, existing curved platforms generally offer only fixed, non-adjustable curvatures, hindering systematic investigation of their effects on stem cell fate. Here, we design and propose shape-memory polymer (SMP) microspheres as a tunable curved platform for culturing bone marrow stromal cells (BMSCs), a good candidate in tissue engineering owing to their self-renewal capacity and multi-lineage differentiation potential. After programming by controlling deformation strains, SMP microspheres transform into ellipsoidal shapes with different curvatures (aspect ratios), constructing tunable curved surfaces for BMSCs. Results indicate that BMSCs cultured on surfaces with larger curvature (smaller aspect ratio) undergo greater nuclear deformation, and vice versa. Furthermore, the curved surfaces provided by the microspheres enhance osteogenic differentiation more effectively than flat films; the larger the curvature (the smaller the aspect ratio), the stronger the promoting effect on osteogenic differentiation. This work will inspire the integration of curved surfaces into cell platforms and scaffolds and provide a shape-memory strategy for curvature adjustment. STATEMENT OF SIGNIFICANCE: This work aims at the overlooked role of substrate curvature in regulating bone marrow stromal cells (BMSCs) fate by engineering shape-memory polymer (SMP) microspheres as an emerging platform for providing tunable curvatures, overcoming the limitation that existing platforms usually offer non-adjustable curvatures, hindering systematic analysis of the effects of curvature on BMSCs fate. SMP microspheres are programmed into ellipsoidal shapes with varying curvatures, and it is found that larger curvature induces greater BMSCs nuclear deformation. Crucially, curved surfaces significantly enhance BMSCs osteogenic differentiation compared to flat surfaces, with a curvature-dependent manner; larger curvature shows stronger promotion effect on osteogenic differentiation. This work develops a curvature-tunable cell substrate using SMP microspheres; it will inspire the integration of curvature cues into tissue scaffolds and curvature adjustment by shape-memory technology.

The permanent nature of bare metal and drug eluting stents can lead to serious long-term complications such as neoatherosclerosis and late stent thrombosis. Magnesium (Mg) based bioabsorbable metal stents, with the ability to provide temporary support to stenosed arteries and harmlessly degrade, are in position to be the 4^th revolution of interventional cardiology. Mg materials are known to be sensitive to biological factors, however this has been understudied with respect to hyperlipidemia. In this study, two distinct WE-series (Mg-Y-Nd) alloy wires (WE43 and WE22) were implanted into the abdominal aorta of wild-type and hyperlipidemic apolipoprotein E knockout (ApoE^-/-) mice for 10 days to investigate the acute corrosion response. We report increased corrosion in ApoE^-/- mice for both alloys, resulting in wire breakage for 50% of WE43 (n=4) and 75% of WE22 implants (n=4) in ApoE^-/- mice compared to 0% in wild-type mice for each alloy (n = 4 WE43 and n=4 WE22). Additionally, human low- and high-density (LDL/HDL) lipoproteins were used to study the in vitro corrosion behavior of WE-series alloys. We report increased acute corrosion of WE43 (6.2 ± 0.7 mm/yr in lipoprotein-supplemented DMEM vs 1.5 ± 0.3 mm/yr in DMEM) and decreased Ca and Mg in the oxide layer of wires corroded in lipoprotein-supplemented medium. Here, LDL and HDL are shown to impact Mg alloy biocorrosion in a dose- and species-dependent manner. Based on our observations, we propose a general mechanism for lipoprotein-mediated Mg corrosion driven by differential chelation of alloying elements specific to each lipoprotein species. STATEMENT OF SIGNIFICANCE: Patients with narrowed or blocked arteries currently receive permanent metal stents, which can lead to long-term complications such as in-stent restenosis and neoatherosclerosis. Bioabsorbable magnesium (Mg) stents degrade over time, reducing the long-term risks, however studies show these materials are sensitive to biological factors. The interactions between cholesterol, which is often increased in patients with atherosclerosis, and Mg-based materials have not been studied. In this study, clinically relevant Mg-alloys are implanted in hyperlipidemic apolipoprotein E knockout mice to investigate the role of increased cholesterol on Mg biocorrosion in vivo. Human low- and high-density lipoproteins are used to investigate the role of lipoproteins on clinically relevant Mg-alloy biocorrosion in vitro.