Biomaterials最新文献

{"title":"A protective growth factor delivery strategy based on polyphenol-protein self-assembly to promote inflammatory bone regeneration","authors":"Ling Li ,&nbsp;Fei Gao ,&nbsp;Huanrong Zhang ,&nbsp;Yang Yu ,&nbsp;Baojin Ma ,&nbsp;Shaohua Ge","doi":"10.1016/j.biomaterials.2025.123272","DOIUrl":"10.1016/j.biomaterials.2025.123272","url":null,"abstract":"<div><div>The efficacy of growth factor delivery-based therapies for bone tissue regeneration is frequently undermined by oxidative stress, especially under inflammatory conditions, which results in structure damage and function inactivation of growth factors. Herein, a straightforward and universal protective delivery strategy is proposed by employing the multiple physical interactions between epigallocatechin-3-gallate (EGCG) and growth factors (e.g., neuregulin-1/NRG-1) to efficiently form self-assembled particles (NE APs). NE APs provide sustained release of NRG-1 while protecting it from oxidative damage, preserving its biological functions of cell recruitment, migration, and angiogenesis. Additionally, NE APs leverage EGCG's ability to scavenge reactive oxygen species and maintain mitochondrial homeostasis, while synergistically enhancing TNF/NF-κB/JAK-STAT signaling pathways to support immune responses and osteogenic differentiation. In vivo experiments demonstrated that NE APs create a favorable microenvironment for bone regeneration through stem cell recruitment, angiogenesis, and immune modulation, effectively promoting the repair of inflammatory bone defects. This versatile protective delivery strategy, based on polyphenol and growth factor self-assembly, offers the potential to advance the application of growth factors in regenerative medicine.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123272"},"PeriodicalIF":12.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D bioprinted microfluidic based osteosarcoma-on-a chip model as a physiomimetic pre-clinical drug testing platform for anti-cancer drugs","authors":"Chitra Jaiswal ,&nbsp;Souradeep Dey ,&nbsp;Jayant Prasad ,&nbsp;Raghvendra Gupta ,&nbsp;Manoj Agarwala ,&nbsp;Biman B. Mandal","doi":"10.1016/j.biomaterials.2025.123267","DOIUrl":"10.1016/j.biomaterials.2025.123267","url":null,"abstract":"<div><div>Standard chemotherapeutic regimen for osteosarcoma (OS) treatment often leads to poor therapeutic outcome, primarily due to lack of an adequate representative model reflecting native OS structural and cellular complexity, posing a translational gap. Three-dimensional bioprinting (3D-BP) represents an efficient and advanced technique for precise recapitulation of the structural and cellular complexity of OS tumor microenvironment (TME). In the present study, we employed a dual extrusion-based 3D-BP method to develop an improved <em>in vitro</em> OS model consisting of both tumor and stromal components. Additionally, a human physiomimetic microfluidic bioreactor is introduced to mimic the dynamic TME and provide physiologically relevant mechanical stimulation to the cells. The model named TC-OS _Dynamic model, demonstrated close resemblance to native OS-TME, validated by <em>in vitro</em> studies. Continuous media flow provided mechanical stimulation in the form of shear stress, positively influencing the growth and aggressiveness of OS. Further, drug screening with the model anticancer drugs (doxorubicin, <em>cis</em>-platin, sorafenib) demonstrated enhanced sensitivity in TC-OS _Dynamic model as compared to TC-OS _Static model, emphasizing enhanced mass transfer, availability and distribution of anticancer drug due to continuous media flow. Overall, TC-OS _Dynamic model holds significant potential as a platform in future for high throughput pre-clinical screening of anticancer drugs.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123267"},"PeriodicalIF":12.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implant derived high local concentration of magnesium inhibits tumorigenicity of osteosarcoma","authors":"Gencheng Gong ,&nbsp;He Huang ,&nbsp;Zhipei Tong ,&nbsp;Yufeng Zheng ,&nbsp;Dong Bian ,&nbsp;Yu Zhang","doi":"10.1016/j.biomaterials.2025.123263","DOIUrl":"10.1016/j.biomaterials.2025.123263","url":null,"abstract":"<div><div>Osteosarcoma (OS) is a fatal malignant tumor that occurs in bone, whose main treatment is surgical resection. With anti-tumor and osteogenic effects, Magnesium (Mg) is a promising biodegradable metal for postoperative treatment in OS, however, its anti-OS effect and mechanism still need to be explored. Here, while holding the ability to promote osteogenesis, Mg metal at the same time significantly reduces the proliferation, migration and invasion of various OS cells (UMR106, 143B, K7M2) <em>in vitro</em>. Similarly, it inhibits the growth and lung metastasis of UMR106 induced tumors in xenograft models <em>in vivo</em>. The mRNA-seq analysis shows that Mg significantly inhibits Wnt-pathway (increased APC, Axin2 and GSK3β to induce degradation of β-catenin) in typical OS, which is further verified by western blotting and immunofluorescence analyses. A Mg²⁺ concentration of 240 mg/L, either from Mg metal extract or Mg salt (MgCl₂), equivalently exhibits significantly increased APC, Axin2, GSK3β and decreased β-catenin, and then inhibits tumorigenicity of typical OS cells. This work reveals that a local high concentration of Mg can inhibit OS by down-regulating Wnt-pathway, and meanwhile favors for normal health bone, which demonstrates a new approach and mechanism in the treatment of OS with Mg-based biodegradable metals.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123263"},"PeriodicalIF":12.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"All-in-one design of titanium-based dental implant systems for enhanced soft and hard tissue integration","authors":"Min Xing ,&nbsp;Wenhao Qian ,&nbsp;Kuicai Ye ,&nbsp;Haifeng Zhang ,&nbsp;Jiayin Feng ,&nbsp;Xuanyong Liu ,&nbsp;Jiajun Qiu","doi":"10.1016/j.biomaterials.2025.123251","DOIUrl":"10.1016/j.biomaterials.2025.123251","url":null,"abstract":"<div><div>Enhancing the sealing between titanium abutment and surrounding soft tissue is crucial for preventing peri-implantitis. Meanwhile, exploring non-invasive antibacterial strategies as alternatives for traditional antibiotic therapy is central to improving the effect of peri-implantitis treatment. Furthermore, facilitating effective integration between titanium implant and osteoporotic bone is the cornerstone for ensuring long-term implant stability in patients with osteoporosis. In light of this, this work innovatively constructed multifunctional vertical graphene-based coatings on titanium implants and abutments using plasma-enhanced chemical vapor deposition technology. The results demonstrated that the vertical graphene coatings promoted soft tissue sealing and exhibited inherent antibacterial activities with the bacteriostasis rates of 65.60 % against <em>Staphylococcus aureus</em> (<em>S. aureus</em>) and 43.89 % against <em>Escherichia coli</em> (<em>E. coli</em>) <em>in vitro</em> which could prevent early infections. Moreover, vertical graphene coatings presented photothermal antibacterial effects with the antibacterial rates of 99.99 % and 95.83 % for <em>S. aureus in vitro</em> and <em>in vivo</em>, respectively, and 92.23 % for <em>E. coli in vitro</em> under near-infrared irradiation, which provided a non-invasive and highly effective treatment option for peri-implantitis. Furthermore, teriparatide acetate was loaded on vertical graphene coatings which enhanced osseointegration between titanium implants and osteoporotic bone. By comprehensively considering the critical functional requirements of dental implants and abutments, this work meticulously designed vertical graphene-based coatings on titanium dental implant systems for soft and hard tissue integration. This innovative design demonstrates immense application potential, especially for dental implant restoration in patients with osteoporosis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123251"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the biodegradation kinetics and associated mechanical properties of 3D-printed polycaprolactone during long-term preclinical testing","authors":"Harsha Ramaraju ,&nbsp;Adam S. Verga ,&nbsp;Bennett J. Steedley ,&nbsp;Andrew P. Kowblansky ,&nbsp;Glenn E. Green ,&nbsp;Scott J. Hollister","doi":"10.1016/j.biomaterials.2025.123257","DOIUrl":"10.1016/j.biomaterials.2025.123257","url":null,"abstract":"<div><div>Polycaprolactone (PCL) is a bioresorbable polymer increasingly utilized for customized tissue reconstruction as it is readily 3D printed. A critical design requirement for PCL devices is determining the <em>in vivo</em> bioresorption rate and the resulting change in device mechanics suited for target tissue repair applications. The primary challenge with meeting this requirement involves accurate prediction of degradation in the target tissues. PCL undergoes bulk hydrolytic degradation following first order kinetics until an 80–90 % drop in the starting number average molecular weight (Mn) after 2–3 years <em>in vivo</em>. However, initial polymer architecture, composite incorporation, manufacturing modality, device architecture, and target tissue can impact degradation. In vitro models do not fully capture device degradation, and the limited long-term (2–3 year) models primarily utilize subcutaneous implants. In this study, we investigate the degradation rate of 3D-printed airway support devices (ASDs) comprised of PCL and 4 % hydroxyapatite (HA) when implanted on Yucatan porcine tracheas for two years.</div><div>After one year of degradation, we report a mass loss of less than 1 % and Mn reduction of 25 %. After two years, mass and Mn decreased by 10 % and 50 % respectively. These changes are accompanied by an increase in elastic modulus from 146.7 ± 5.2 MPa for freshly printed ASDs to 291.7 ± 16.0 MPa after one year and 362.5 ± 102.4 MPa after two years. Additionally, there was a decrease in yield strain, and increase in yield stress from implantation to 1-year (p &lt; 0.001). Plastic strain completely diminished by two years, resulting in brittle failure at a yield stress of 12.5 MPa. The significantly lower rate of hydrolysis coupled with hydrolytic embrittlement indicates alternate degradation kinetics compared to subcutaneous models. Fitting a new model for degradation and predicting elastic and damage properties of this new degradation paradigm provide significant advancements for 3D-printed device design in clinical repair applications.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123257"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective and iron-independent ferroptosis in cancer cells induced by manipulation of mitochondrial fatty acid oxidation","authors":"Yan Gao,&nbsp;Zilin Song,&nbsp;Wenxin Gan,&nbsp;Xue Zou,&nbsp;Yaning Bai,&nbsp;Xiuli Zhao,&nbsp;Dawei Chen,&nbsp;Mingxi Qiao","doi":"10.1016/j.biomaterials.2025.123259","DOIUrl":"10.1016/j.biomaterials.2025.123259","url":null,"abstract":"<div><div>Despite the promise of ferroptosis in cancer therapy, selectively inducing robust ferroptosis in cancer cells remains a significant challenge. In this study, manipulation of fatty acids β-oxidation (FAO) by combination of mild photodynamic therapy (PDT) and inhibition of triglycerides (TGs) synthesis was found to induce robust and iron-independent ferroptosis in cancer cells with dysregulated lipid metabolism for the first time. To achieve that, TGs synthesis inhibitor of xanthohumol (Xan) and FAO initiator of tetrakis (4-carboxyphenyl) porphyrin (TCPP) were co-delivered by a nanoplexes composed of pH-responsive amphiphilic lipopeptide C₁₈-pHis₁₀ and DSPE-PEG₂₀₀₀. TCPP was found to rapidly increase the intracellular ROS under laser irradiation without inducing antioxidant response and apoptosis, activating the AMPK in cancer cells and accelerating mitochondrial FAO. Xan fueled the mitochondrial FAO with substrates by suppressing the conversion of fatty acids (FAs) to TGs. This also led to augmented intracellular polyunsaturated fatty acids (PUFAs) and PUFAs-phospholipids levels, increasing the intrinsic susceptibility of cancer cells to lipid peroxidization. As a result, the excessive ROS generated from the sustained mitochondrial FAO caused remarkably lipid peroxidation and ultimately ferroptosis. Collectively, our study provides a new approach to selectively induce iron-independent ferroptosis in cancer cells by taking advantage of dysregulated lipid metabolism.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123259"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vacancies-rich Z-scheme VdW heterojunction as H2S-sensitized synergistic therapeutic nanoplatform against refractory biofilm infections","authors":"Jianwen Dong ,&nbsp;Shuting Zhang ,&nbsp;Yau Kei Chan ,&nbsp;Shuangquan Lai ,&nbsp;Yi Deng","doi":"10.1016/j.biomaterials.2025.123258","DOIUrl":"10.1016/j.biomaterials.2025.123258","url":null,"abstract":"<div><div>Encapsulated in a self-produced negatively charged extracellular polymeric substance (EPS) matrix, the wound infected bacterial biofilms exhibit formidable resistance to conventional positively charged antibiotics and host's immune responses, which can undoubtedly lead to persistent infections and lethal complications. Nevertheless, developing efficacious strategies to root out stubborn biofilm and promote tissue regeneration still remains a challenge. To resolve this dilemma, a versatile vacancies-rich Z-scheme MoSSe Van der Waals heterojunction (MoSSe VdW HJ) is rationally fabricated as nanoplatform for hydrogen sulfide (H₂S)-sensitized synergistic therapy of wound bacterial biofilm infection. The rich anion vacancies and Z-scheme heterostructure make the fabricated MoSSe VdW HJ can effectively augment H₂S, localized hyperthermia, and reactive oxygen species production under the stimulation of biofilm microenvironments (BME) and irradiation of 808 nm near-infrared (NIR) light. Therefore, MoSSe VdW HJ is capable to integrate H₂S gas, chemodynamic, photothermal, and photodynamic therapies to effectively destroy eDNA and polysaccharides in the EPS matrix, thereby breaching the biofilm barrier to eradicate bacteria and facilitate wound healing. The synergistic strategy exhibits superior anti-biofilm and wound repair effects both <em>in vivo</em> and <em>in vitro</em>, thus providing guideline for the development of BME and NIR light activated synergistic therapeutics to fight against refractory biofilm infections.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123258"},"PeriodicalIF":12.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive polymers as stimulus-responsive anti-metastatic combination agents to treat pancreatic cancer","authors":"Sudipta Panja ,&nbsp;Ekta Kapoor ,&nbsp;Kasturi Siddhanta ,&nbsp;Chinmay M. Jogdeo ,&nbsp;Diptesh Sil ,&nbsp;Rubayat I. Khan ,&nbsp;Neha Kumari ,&nbsp;Ling Ding ,&nbsp;Howard E. Gendelman ,&nbsp;Amar B. Singh ,&nbsp;David Oupický","doi":"10.1016/j.biomaterials.2025.123255","DOIUrl":"10.1016/j.biomaterials.2025.123255","url":null,"abstract":"<div><div>The intractable and devastating nature of pancreatic ductal adenocarcinoma (PDAC) necessitates an urgent need for novel therapies. This study presents the development of a novel polymer prodrug system for the combination treatment of PDAC, based on an optimized pharmacologically active anti-metastatic macromolecular carrier, PCQ, conjugated with gemcitabine (GEM). Structure-activity relationship evaluations showed that random PCQ copolymers exhibited superior anti-migratory activity compared to the gradient PCQ analogs. GEM was incorporated into the random PCQ copolymers using disulfide linker to prepare a reduction-responsive prodrug, PCQ(r)6-SS-GEM12. The resultant therapeutic system presents a pharmacologically active delivery strategy that targets both the proliferative and the metastatic phenotype in PDAC. The PCQ(r)6-SS-GEM12 prodrug demonstrated a selective release of GEM under the reductive tumor environment leading to a significant inhibition of tumor growth with pronounced anti-metastatic effect. Collectively, our data show that the combination of anti-metastatic PCQ and cytotoxic GEM-based reduction-responsive prodrug polymer offers an innovative strategy to treat PDAC.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123255"},"PeriodicalIF":12.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioprinted high cell density liver model with improved hepatic metabolic functions","authors":"Ting-Yu Lu ,&nbsp;Yichun Ji ,&nbsp;Cheng Lyu ,&nbsp;Erin Nicole Shen ,&nbsp;Yazhi Sun ,&nbsp;Yi Xiang ,&nbsp;Tobias Meng-Saccoccio ,&nbsp;Gen-Sheng Feng ,&nbsp;Shaochen Chen","doi":"10.1016/j.biomaterials.2025.123256","DOIUrl":"10.1016/j.biomaterials.2025.123256","url":null,"abstract":"<div><div><em>In vitro</em> liver tissue models are valuable for studying liver function, understanding liver diseases, and screening candidate drugs for toxicity and efficacy. While three-dimensional (3D) bioprinting shows promise in creating various types of functional tissues, current efforts to engineer a functional liver tissue face challenges in replicating native high cell density (HCD) and maintaining long-term cell viability. HCD is crucial for establishing the cell-cell interactions necessary to mimic the liver's metabolic and detoxification functions. However, HCD bioinks exacerbate light scattering in light-based 3D bioprinting. In this study, we incorporated iodixanol into our bioink formulation to minimize light scattering, enabling the fabrication of hepatic tissue constructs with an HCD of 8 × 10⁷ cells/mL while maintaining high cell viability (∼80 %). The printed dense hepatic tissue constructs showed enhanced cell-cell interactions, as evidenced by increased expression of E-cadherin and ZO-1. Furthermore, these constructs promoted albumin secretion, urea production, and P450 metabolic activity. Additionally, HCD hepatic tissue inactivated the YAP/TAZ pathway via cell-cell interactions, preserving primary hepatocyte functions. Further screening revealed that hepatocytes in the dense model were more sensitive to drug treatments than those in a lower-density hepatic model, highlighting the importance of HCD in recapitulating the physiological drug responses. Overall, our approach represents a significant advancement in liver tissue engineering, providing a promising platform for the development of physiologically relevant <em>in vitro</em> liver models for drug screening and toxicity testing.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123256"},"PeriodicalIF":12.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase-adapted metal ion supply for spinal cord repair with a Mg–Zn incorporated chimeric microsphere","authors":"Xiangyu Liu ,&nbsp;Biao Ma ,&nbsp;Sihan Hu ,&nbsp;Dandan Li ,&nbsp;Chun Pan ,&nbsp;Zhuobin Xu ,&nbsp;Hao Chen ,&nbsp;Yongxiang Wang ,&nbsp;Huihui Wang","doi":"10.1016/j.biomaterials.2025.123253","DOIUrl":"10.1016/j.biomaterials.2025.123253","url":null,"abstract":"<div><div>Dynamic alterations in metal ion concentrations are observed in the pathological process of spinal cord injury (SCI). Hence, strategically supplying metal ions in a phase-adapted manner is promising to facilitate injured spinal cord repair by preventing pathological damage. To achieve this, a chimeric hydrogel microsphere with Mg²⁺-crosslinked methacrylate gelatin as the \"shell\" and Zn²⁺-loaded poly (lactic-co-glycolic acid) (PLGA) as the \"core\" was designed. The chimeric microspheres allow continuous delivery of Mg²⁺ or Zn²⁺ at the exact required phase in SCI pathological process. Early release of Mg²⁺ reduced inflammation by diminishing the secretion of proinflammatory cytokines due to changes in macrophage polarization, which further suppressed scar formation to create an ideal space for neural regeneration. The subsequently released Zn²⁺ at the late phase effectively promoted neural cell proliferation and regeneration, which was accompanied by activation of mature neurons, interneurons, and motor neurons, leading to significant behavioral recovery. Thus, this study underscores the critical role of metal ions at different phases of injured spinal cord repair and describes the construction of an injectable chimeric hydrogel microsphere carrying distinct metal ions with a core-shell structure. Chimeric microspheres overcome the discrepancy between the inflammatory response and neural regeneration and are a promising therapeutic strategy for injured spinal cord repair.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123253"},"PeriodicalIF":12.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}