ACS Biomaterials Science & Engineering最新文献

{"title":"Reactive Oxygen Species-Responsive Gel-Based Microneedle Patches with Antimicrobial and Immunomodulating Properties for Oral Mucosa Disease Treatment.","authors":"Xuancheng Zhang, Guannan Zhong, Shiyuan Peng, Chuankai Zhang, Bo Li, Zhaoxing Xia, Yujing Zhu, Gang Tao, Rui Cai, Xiaomei Xu","doi":"10.1021/acsbiomaterials.4c02050","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c02050","url":null,"abstract":"<p><p>Oral ulcer wounds are difficult to heal due to bacterial infections, persistent inflammatory responses, and excessive reactive oxygen species (ROS). Therefore, the elimination of bacteria, removal of ROS, and reduction of inflammation are prerequisites for the treatment of mouth ulcer wounds. In this study, oligomeric proanthocyanidins (OPC) and 3-(aminomethyl)phenylboronic acid-modified hyaluronic acid (HP) were used to form polymer gels through dynamic covalent borate bonds. Minocycline hydrochloride (MH) was then loaded into the polymer gel, and a multifunctional MH/OPC-HP microneedles (MNs) with ROS-responsive properties was prepared using a vacuum method. The MH/OPC-HP MNs can rapidly release MH in a diffusive manner and sustainably release OPC in response to ROS. The gel-based MH/OPC-HP MNs extended the retention of OPC in oral ulcers, leading to prolonged ROS scavenging effects. Cytocompatibility and hemocompatibility tests showed that MH/OPC-HP MNs had good biocompatibility. Antibacterial experiments demonstrated that MNs loaded with MH exhibited excellent antibacterial effects. In vitro experiments indicated that MH/OPC-HP MNs could effectively clear ROS, reduce oxidative stress damage, inhibit M1-type macrophage polarization, and induce M2-type polarization. Furthermore, in vivo experiments revealed that MH/OPC-HP MNs could inhibit pro-inflammatory cytokines, promote neovascularization, accelerate epithelial healing of ulcers, and significantly promote healing in a rat model of oral ulcer wound infection. In summary, MH/OPC-HP MNs hold promise as a therapeutic strategy for enhancing the healing of oral ulcer wounds.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thiol-Enhanced Interfacial and Internal Deposition of Metal-Polyphenol Networks for Permanent Hair Dyeing.","authors":"Chengge Fang, Ling Ma, Timson Chen, Ya Chen, Zhizhen Li, Xiaodong Yan, Jing Wang","doi":"10.1021/acsbiomaterials.4c01973","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01973","url":null,"abstract":"<p><p>Metal polyphenolic networks (MPNs) are becoming more and more attractive for nontoxic hair dyeing, but their coloring effect is not satisfactory because of the limited interfacial deposition and the absence of internal deposition. Moreover, there is a lack of understanding of the driving factors of the interfacial deposition of MPNs on hair. Herein, we develop a simple yet efficient strategy that transforms disulfide bonds of the hair into thiol groups by thioglycolic acid (TGA) to highly enhance the coloring effect of MPNs at a low temperature. The highly reactive thiol groups react with Fe²⁺ to form Fe-S bonds, greatly facilitating the interfacial and internal deposition of MPNs and thus resulting in rapid coloration and high darkness. Moreover, the TGA-assisted MPNs-dyed (TGA/MPN) hair shows high resistance to washing with a shampoo. Further, it is found that the connection of thiol groups to the MPNs endows the TGA/MPN hair with similar mechanical and structural properties to the natural white hair and even enables simultaneous hair dyeing and perming. This study offers a novel universal strategy for hair dyeing and permeation with MPNs.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Traditional Chinese Medicine-Based Nanoformulations for Enhanced Photothermal Therapy of Cancer.","authors":"Lin Yu, Xueying Qin, Bing Liang, Jingjing Liu","doi":"10.1021/acsbiomaterials.4c01612","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01612","url":null,"abstract":"<p><p>Photothermal therapy (PTT) has shown promise in the ablation of small, unresectable tumors by boosting the tumor's temperature above 50 °C. However, the high local temperature-induced cancer cell necrosis could create severe local inflammation, which may deteriorate normal tissues and increase tumor spreading. Although mild photothermal therapy (MPTT) at 42-45 °C could avoid the undesired side effect to some extent with minimal nonspecific heat diffusion, the self-protective behavior of tumors during MPTT results in an unsatisfactory therapeutic effect. Inspired by the widespread applications of traditional Chinese medicine (TCM) in various ailments, we also extensively explored the use of TCM in PTT and MPTT. In this Review, we summarize the application and function of TCM in PTT and MPTT, including the following: (1) TCM improves the performance of PTT and MPTT by elevating the photothermal conversion ability of photothermal agents (PTAs) and overcoming the self-protective effect of tumors, (2) PTT enhances TCM-based chemotherapy by improving the sensitivity and cellular uptake of TCM in tumors, and (3) natural TCM and metal-chelated TCM-based nanoparticles could directly act as PTAs for carrier-free combination therapy. We expect this Review will further illuminate TCM's utility and applicability in cancer treatment and create new combination strategies for theragnostic use.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-Locked Enzyme-Activatable Fluorescence Probes for Precise Bioimaging.","authors":"Yang Liu, Yuchen Yao, Junhui Sha, Gaolin Liang, Xianbao Sun","doi":"10.1021/acsbiomaterials.4c01858","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01858","url":null,"abstract":"<p><p>Real-time visualization of endogenous enzymes not only helps reveal the underlying biological principles but also provides pathological information for cancer/disease diagnosis and even treatment guidance. To this end, enzyme-activatable fluorescence probes are frequently fabricated that turn their fluorescence signals \"on\" exclusively at the enzyme-rich region, thus enabling noninvasive and real-time imaging of enzymes of interest at the molecular level with superior sensitivity and selectivity. However, in a complex biological context, commonly used single enzyme-activatable (i.e., single-locked) probes may suffer from \"false positive\" signals at healthy tissues and be insufficient to accurately indicate the occurrence of certain diseases. Therefore, dual-locked fluorescence probes have been promoted to address these issues. Using dual enzymes (or an enzyme with another stimulus) as \"keys\", they permit simultaneous detection of distinct biomarkers, offering significantly enhanced imaging precision toward certain biological events. Considering that recent reviews on these probes remain scarce, we thus provide this review. We summarize the recent progress, particularly highlighting the breakthroughs in the last three years, and discuss the challenges in this field.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulating Single Phasic Silicorhenanite (α- and β-Na₂Ca₄(PO₄)₂SiO₄) Bioactive Glass Materials Competing with Commercial Crystalline Hydroxyapatite Bone Mineral for Biomedical Applications.","authors":"Vijayakumari Sugumaran, Annamalai Kamalakkannan, Elakkiya Krishnamoorthy, Gosala Radha, Balakumar Subramanian","doi":"10.1021/acsbiomaterials.4c01219","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01219","url":null,"abstract":"<p><p>Hydroxyapatite (HAP) is a well-known medically renowned bioactive material known for its excellent biocompatibility and mechanical stability, but it lacks fast bioactivity. The restricted release of ions from hydroxyapatite encourages the search for a faster bioactive material that could replicate other properties of HAP. A new sol-gel-mediated potentially bioactive glass material that could mimic the structure of HAP but can surpass the performance of HAP bioactively has been formulated in this study. Lefebvre et al. suggested that the silicorhenanite phase with the formula Na₂Ca₄(PO₄)₂SiO₄ is isostructural to hydroxyapatite; however, data in support of this hypothesis are scant. This study succeeds in developing fast apatite-growth-inducing bioactive glass particles similar to the structure of hydroxyapatite. Also, for the first time, the existence and evolution of two forms of silicorhenanite (α- and β-Na₂Ca₄(PO₄)₂SiO₄) have been unraveled, and their properties have been explored. The effect of calcination temperature on the phase formation of the biomaterial is notified by looking into the result that heat treatment to 900 °C resulted in α-Na₂Ca₄(PO₄)₂SiO₄ (Sili 900) and 1000 °C yielded β-Na₂Ca₄(PO₄)₂SiO₄ (Sili 1000). This study conveys a new finding that the hydroxyapatite is isostructural to β-Na₂Ca₄(PO₄)₂SiO₄ but not to α-Na₂Ca₄(PO₄)₂SiO₄. Raman spectroscopic analysis proved this structural similarity of Sili 1000 and c-HAP, with relative spectra possessing phosphate bands and the irrelevance of Sili 900 to Sili 1000 and c-HAP. The <i>in vitro</i> MTT assay using NIH 3T3 fibroblasts and <i>in vivo</i> wound healing study confirm the enhanced bioactivity and compatibility of Sili 900 and Sili 1000 compared to c-HAP, favored by the presence of a silica matrix and semicrystallinity. pH analysis proved the rapid ionic leaching out from Sili 900 and Sili 1000 and the faster reactivity of Sili 1000 with the fluid. This rapid burst of ions enhances the clotting ability of the Sili 1000 bioactive material and can be a good ibuprofen drug carrier, which is a potential challenger to hydroxyapatite.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osseointegration of 3D-Printable Polyetheretherketone-Magnesium Phosphate Bioactive Composites for Craniofacial and Orthopedic Implants.","authors":"Surendrasingh Y Sonaye, Renan Dal-Fabbro, Marco C Bottino, Prabaha Sikder","doi":"10.1021/acsbiomaterials.4c01597","DOIUrl":"10.1021/acsbiomaterials.4c01597","url":null,"abstract":"<p><p>Polyetheretherketone (PEEK) is a high-performance polymer material for developing varying orthopedic, spine, cranial, maxillofacial, and dental implants. Despite their commendable mechanical properties and biocompatibility, the major limitation of PEEK implants is their low affinity to osseointegrate with the neighboring bone. Over the last two decades, several efforts have been made to incorporate bioactive components such as bioceramic particles in PEEK to enhance its osseointegration capacity. However, one major limitation is that the bioceramic particles embedded in the PEEK matrix can degrade over time, compromising the implant's long-term bioactivity and mechanical properties. To address this limitation, in this study, we utilized a unique bioceramic known as amorphous magnesium phosphate (AMP). AMP is a metastable phase of magnesium phosphate that nanocrystallizes in a physiological medium to stable bioactive phases exhibiting low degradation kinetics and high bioactivity. Thus, based on this property of AMP, we hypothesize that AMP-PEEK composites will exhibit sustained biodegradation kinetics, help maintain long-term osseointegration, and inhibit mechanical property degradation. Herein, we reported on a detailed <i>in vitro</i> degradation analysis of the developed AMP-PEEK composite 3D-printable filaments and the osseointegration capacity when implanted in a rat femoral model. The AMP-PEEK composite demonstrates controlled degradation kinetics, with tensile strength progressively decreasing from 120 to 70 MPa over a 28-day period due to hydrolytic degradation, which aligns with its role as a bioresorbable material. Notably, our findings confirm that AMP-PEEK composite osseointegration is on par with clinical gold-standard titanium implants. Thus, this study establishes a unique magnesium phosphate and PEEK-based bioactive composite material with promising potential for developing standalone dental and craniofacial implants.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal Administrations of AP39-Loaded Liposomes Selectively Deliver H2S to Neuronal Mitochondria to Protect Neonatal Hypoxia-Ischemia by Targeting ERK1/2 and Caspase-1.","authors":"Yan Song, Nianlu Li, Qian Luo, Dexiang Liu, Zhen Wang","doi":"10.1021/acsbiomaterials.4c02282","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c02282","url":null,"abstract":"<p><p>Mitochondrial dysfunction contributes to the pathology of hypoxia-ischemia (HI) brain damage by aberrant production of ROS. Hydrogen sulfide (H₂S) has been demonstrated to exert neuroprotective effects through antioxidant mechanisms. However, the diffusion of H₂S <i>in vivo</i> is not specifically targeted and may even be systemically toxic. In this study, based on mitochondria-targeted H₂S donor AP39, we fabricated liposomes encapsulating AP39 (AP39@Lip) via intranasal delivery to improve functional recovery after HI brain injury. This study presents that intranasal administration of AP39@Lip was capable of attenuating acute brain injury by inhibiting mitochondrial dysfunction, apoptosis, neuroinflammation, and ROS production in the lesional cortex 3 days after HI brain injury. Similarly, AP39@Lip was observed to restore both short- and long-term function following HI injury without obvious toxicity. Mechanistically, the therapeutic effects of AP39@Lip mainly relied on its colocalization with neuronal mitochondria 24 h after administration and reversed H₂S levels in the lesional cortex. Moreover, molecular docking and cellular thermal shift assay suggest that AP39 inhibited the activation of ERK1/2 and caspase-1 by directly binding to ERK1/2 or caspase-1. These results indicate that intranasal administration of AP39@Lip selectively delivered H₂S to neuronal mitochondria and mitigated mitochondrial damage following HI insult by targeting ERK1/2 and caspase-1.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into Calcium Phosphate Formation Induced by the Dissolution of 45S5 Bioactive Glass.","authors":"Elkin Lopez-Fontal, Stéphane Gin","doi":"10.1021/acsbiomaterials.4c01680","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01680","url":null,"abstract":"<p><p>Although models have been proposed to explain the mechanisms of bioglass (BG) dissolution and subsequent calcium phosphate (CaP) mineralization, open questions remain. The processes in which phase transition occurs in aqueous solutions and their dynamics remain underexplored partly because traditional instruments/techniques do not allow for direct observations at the adequate time and length scales at which such phase transformations occur. For instance, given the crucial role of the silica gel in CaP formation during BG dissolution, uncertainty exists about how such a silica gel forms on the BG surface. In the case of CaP formation driven by BG dissolution, questions can also be added, i.e., how CaP develops into an apatitic-like structure, how many transient phases there are, and, in general, phenomena occurring in the solid-liquid interface during BG dissolution. Several approaches were taken to study CaP mineralization driven by BG dissolution, mainly examining the solid-liquid interface and the BG after-reaction surface. This paper focuses on gaining insight into silica gel formation on the BG's surface during dissolution. Electron microscopy techniques were used, including scanning electron microscopy and focused ion beam cross sections. Other analysis techniques, such as time-of-flight secondary ion mass spectrometry, were utilized. Cross sections of reacted BG-blocks gave essential insights into the BG dissolution, particularly its strong dependency on experimental conditions, and tentative evidence has shown that soluble silica from BG dissolution may not reprecipitate/repolymerize on BG blocks' surface; thus, we wonder where it precipitates. Additionally, complementary analysis techniques determined that CaP, during BG dissolution, transitions from amorphous calcium phosphate to a calcium-deficient nanocrystalline apatitic structure with minimal contents of Si⁴⁺ and Na⁺ ions that may be molecularly part of CaP. The Hench model has been the core guide for BG dissolution and subsequent CaP formation for many years. However, this study shows tentative evidence that contributes to and somewhat differs from it.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modern Approach to Testing the Biocompatibility of Osteochondral Scaffolds in Accordance with the 3Rs Principle─Preclinical <i>In Vitro</i>, <i>Ex Vivo</i>, and <i>In Vivo</i> Studies Using the Biphasic Curdlan-Based Biomaterial.","authors":"Katarzyna Klimek, Sylwia Terpilowska, Agnieszka Michalak, Rafal Bernacki, Aleksandra Nurzynska, Magali Cucchiarini, Marta Tarczynska, Krzysztof Gaweda, Stanisław Głuszek, Grazyna Ginalska","doi":"10.1021/acsbiomaterials.4c01107","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01107","url":null,"abstract":"<p><p>The aim of this work is to provide a comprehensive set of biological tests to assess the biomedical potential of novel osteochondral scaffolds with methods proposed to comply with the 3Rs principle, focusing here on a biphasic Curdlan-based osteochondral scaffold as a promising model biomaterial. <i>In vitro</i> experiments include the evaluation of cytotoxicity, mutagenicity, and genotoxicity referring to ISO standards, the assessment of the viability and proliferation of human chondrocytes and osteoblasts, and the estimation of inflammation after direct contact of biomaterials with human macrophages. <i>Ex vivo</i> experiments include assessments of the response of the surrounding osteochondral tissue after incubation with the implanted biomaterial. <i>In vivo</i> experiments involve an evaluation of the toxicity and regenerative potential of the biomaterial in zebrafish (larvae and adults) and in osteochondral defects in dogs (veterinary patients). The applied set of tests allows us to show that the Curdlan-based scaffold does not induce cytotoxicity (cell viability close to 100%), mutagenicity (the level of reversion is not 2× higher compared to the control), and genotoxicity (it does not exhibit any change in chromosomal aberration; the frequency of micronuclei, micronucleated binucleated cells, and cytokinesis-block proliferation index is comparable to the control; moreover, it does not cause the formation of comets in cells). This biomaterial also promotes the viability and proliferation of chondrocytes and osteoblasts (the OD values between the fourth and seventh day of incubation increase by approximately 1.6×). The Curdlan-based scaffold stimulates only a transient inflammatory response <i>in vitro</i> and <i>ex vivo</i>. This biomaterial does not cause <i>Danio rerio</i> larvae malformation and also enables proper regeneration of the caudal fin in adults. Finally, it supports the regeneration of an osteochondral defect in veterinary patients. Thus, this is a proposal to use alternative methods for biological assessment of osteochondral scaffolds as opposed to commonly used tests using large numbers of laboratory animals.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging-Induced Discrepant Response of Fracture Healing is Initiated from the Organization and Mineralization of Collagen Fibrils in Callus.","authors":"Fa Liu, Yiwei Hu, Yuzhi Zhang, Chenxi Ren, Feng Qiao, Hui Yang, Huiyun Xu, Pengfei Yang","doi":"10.1021/acsbiomaterials.4c01490","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01490","url":null,"abstract":"<p><p>Fracture healing is a complex process during which the bone restores its structural and mechanical integrity. Collagen networks and minerals are the fundamental components to rebuild the bone matrix in callus. It has been recognized that bone quality could be impaired during aging. However, how the structural and mechanical recovery of fracture healing is influenced by aging, particularly from the perspective of organization and mineralization of the collagen network in callus, remains unclear. A tibial fracture model was established for both the young (5 weeks) and aged mice (68 weeks). On the 21st day postfracture, the characteristics of the collagen network, mineralization, and the nanoscale mechanical properties of the callus were assessed. The results indicated that aging postpones the fracture healing process, leading to incomplete microstructure, less mineral content and mineralization, and weaker mechanical properties of callus. In the aged mice, the internal fixation and mechanical immobilization promoted the mineralization of callus by increasing mineral crystal length and mineral-to-matrix ratio by 48 and 42% compared to the internal fixation and free movement control group, respectively. By contrast, in the young mice, the internal fixation and mechanical immobilization induced disordered collagen fibrils and decreased the crystal length and mineral-to-matrix ratio by 32 and 36%, compared to the internal fixation and free movement control group, respectively. The present findings suggested that the aging-induced structure and mechanical differences of callus during fracture healing initiate from the organization and mineralization of collagen fibrils. Multiscale structural and mechanical analysis suggested mechanical immobilization is beneficial to the structure, composition, and mechanics of callus in the aged mice while impairing the organization and mineralization of collagen fibril in the callus of the young mice. These findings suggested that different mechanical intervention strategies should be adopted for fracture healing at different ages, which provides valuable insights for the clinical treatment of bone fracture.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}