Acta Biomaterialia最新文献

{"title":"Reversible light-responsive protein hydrogel for on-demand cell encapsulation and release","authors":"Om Prakash Narayan ,&nbsp;Jiawei Dong ,&nbsp;Miao Huang ,&nbsp;Liqiang Chen ,&nbsp;Lu Liu ,&nbsp;Vivian Nguyen ,&nbsp;Abdul Vehab Dozic ,&nbsp;Xiangping Liu ,&nbsp;Huiliang Wang ,&nbsp;Qian Yin ,&nbsp;Xin Tang ,&nbsp;Juan Guan","doi":"10.1016/j.actbio.2025.01.012","DOIUrl":"10.1016/j.actbio.2025.01.012","url":null,"abstract":"<div><div>The design of biomaterials that can reconfigure on-demand in response to external stimuli is an emerging area in materials research. However, achieving reversible assembly of protein-based biomaterials by light input remains a major challenge. Here, we present the engineering of a new protein material that is capable of switching between liquid and solid state reversibly, controlled by lights of different wavelengths. The materials are created by incorporating a light-responsive mutant Dronpa protein domain into the backbone of Elastin-Like Proteins (termed DELPs). We show that the DELP material can respond to light and undergo multiple cycles of switching between hydrogel and solution, outperforming the conventional irreversible materials. Additionally, the material is biocompatible with long-term cell proliferation in both adherent and suspension cells. Building on the reversible assembly of the material, we demonstrate efficient cell encapsulation and release upon light triggers. The design principle of incorporating a light-responsive protein element into a structural protein matrix, as demonstrated in this work enables, a broad range of other applications that require adaptive materials to intelligently interface with dynamic biological systems and environments.</div></div><div><h3>Statement of significance</h3><div>This work generates a new class of “smart” biomaterials that uniquely switches between liquid and gel states in response to light input. Light input can be precisely delivered in space and time, highly tunable through wavelengths, intensities, and durations of light exposure. In prior research, light-responsive biomaterials are mostly irreversible, limiting their use to only uni-directional applications and the materials cannot be re-used. In contrast, this material robustly displays reversible switching between liquid and gel using a light-responsive crosslinker. Furthermore, the material is biocompatible, programmable, and suitable for broad applications including but not limited to cell encapsulation, controlled release, tissue engineering, and cell/tissue mechanobiology.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 202-214"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973733","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":"Cocktail strategy-based nanomedicine: A synergistic cascade of starvation, NIR-II photothermal, and gas therapy for enhanced tumor immunotherapy","authors":"Lianying Zhang ,&nbsp;Xiaotong Chen ,&nbsp;Beixian Zhou ,&nbsp;Wei Meng ,&nbsp;Haifeng Zeng ,&nbsp;Yongjian Chen ,&nbsp;Guoqin Huang ,&nbsp;Yingshan Zhang ,&nbsp;Huimin Wang ,&nbsp;Ming Chen ,&nbsp;Jinxiang Chen","doi":"10.1016/j.actbio.2024.11.011","DOIUrl":"10.1016/j.actbio.2024.11.011","url":null,"abstract":"<div><div>Immunotherapy has emerged as a highly promising strategy in the realm of cancer treatment, wherein immunogenic cell death (ICD) is considered a potential trigger for anti-tumor immunity by inducing adaptive immunity to dying cell antigens. This process is often accompanied by the exposure, active secretion, or passive release of a large number of damage-associated molecular patterns (DAMPs), which activate dendritic cells (DCs) and enhance their antigen-presenting capacity. Subsequently, it promotes the recruitment and activation of cytotoxic T lymphocytes, ultimately leading to tumor growth inhibition. In addition, polarizing the M2 phenotype of tumor-associated macrophages (TAMs) to the M1 phenotype is another way to activate anti-tumor immunity, which can further enhance the effect of anti-tumor immunotherapy. In this study, we engineered a composite nanoparticle of UiO-66-NH₂@Gold nanoshells@GOx-P-Arg (denoted as UGsGP). The gold nano shells in UGsGP exhibit a broad Near-Infrared-II (NIR-II) absorption to give a high photothermal conversion efficiency and achieve photothermal therapy (PTT). The GOx in UGsGP involves the breakdown of glucose, which results in a decrease in ATP levels and an inhibition of HSP90 and HSP70 production, ultimately enhancing the heat sensitivity of the tumor for PTT. In addition, GOx-mediated starvation therapy by glucose exhaustion produces a substantial amount of hydrogen peroxide (H₂O₂), which can then react with P-Arg to produce intratumoral NO Thus, the synergistic effect of PTT resensitization, the photothermally-enhanced GOx-mediated starvation, and NO-based gas therapy promote the induction of ICD and the polarization of TAMs. The combination therapy exhibits significant antitumor effects both in vitro and in vivo.</div></div><div><h3>Statement of significance</h3><div>(1) Gold nanoshells on the surface of UiO-66-NH₂ display a broad absorption spectrum ranging from 900 to 1700 nm, combined with a high photothermal conversion efficiency of 74.0 %, demonstrating their remarkable ability to harness and convert light energy into heat for effective tumor ablation.</div><div>(2) Under laser irradiation, GOx within the UGsGPs effectively consumes glucose, increasing intratumoral H₂O₂ levels, which then reacts with P-Arg to produce NO within the tumor. Concurrently, the reduction in ATP levels suppresses HSP90 and HSP70 production, thereby enhancing the tumor's sensitivity to photothermal therapy.</div><div>(3) The synergistic combination of NO gas therapy, starvation therapy, and PTT promotes ICD induction and TAM polarization, thereby improving the therapeutic outcomes for primary and distant tumors.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 316-333"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866568","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":"380 MPa-30% grade biodegradable Zn-Mn-Mg-Ca alloy: Bimodal grain structure, large work-hardening strain, and enhanced biocompatibility","authors":"Xiang-Min Li ,&nbsp;Zhang-Zhi Shi ,&nbsp;Jia-You Zhang ,&nbsp;Chao Zhou ,&nbsp;Lu-Ning Wang","doi":"10.1016/j.actbio.2024.12.050","DOIUrl":"10.1016/j.actbio.2024.12.050","url":null,"abstract":"<div><div>Strain softening is a common issue for high-strength biodegradable Zn alloys. We developed Zn-0.6Mn-0.05Mg-0.05Ca alloy with a bimodal grain structure by extrusion and caliber rolling, refer to as ZMMC063 (CRD). The alloy exhibits the best strength-ductility synergy among Zn-Mn based alloys, which shows a yield strength of 386 MPa, an ultimate tensile strength of 443 MPa, and an elongation rate of 31%. This is the first 380 MPa-30% grade Zn-Mn based alloy, surpassing the previous reported Zn alloy with 320 MPa-20% grade. Its work-hardening strain reaches as high as 11.6%, which is 4 times greater than that of other 300 MPa Zn-Mn based alloys. This is owing to hetero-deformation induced strengthening effect of the bimodal grain. Additionally, it demonstrates for the first time that micro-galvanic corrosion happens between coarse and fine Zn grains, thereby accelerating degradation of the alloy. This provides a feasible protocol for controlling degradation of Zn alloys. Compared with the extruded Zn-0.6Mn-0.05Mg-0.05Ca alloy, refer to as ZMMC063 (HE), the increased release of Mg²⁺ and Ca²⁺ ions in ZMMC063 (CRD) improves tolerance of MC3T3-E1 cells to Zn²⁺. Consequently, ZMMC063 (CRD) shows higher antibacterial abilities against <em>E. coli</em> and <em>S. aureus</em>, meanwhile much less toxicity to MC3T3-E1 cells. Synergistic effect of Zn²⁺, Mg²⁺ and Ca²⁺ ions promote expression of ALP, <em>COl-1, OCN</em> and <em>Runx-2</em>, so that ZMMC063 (CRD) exhibits better ability to induce osteogenic differentiation. This paper suggests that ZMMC063 (CRD) is a promising candidate for orthopedic implants.</div></div><div><h3>Statement of significance</h3><div>Previously the highest yield strength-elongation level of Zn-Mn based alloys is 320 MPa-20% grade. At such a high strength, the alloys’ work-hardening strain (Ewh) values are below 4%. To further improve comprehensive properties of Zn-Mn based alloys, 380 MPa-30% grade Zn-0.6Mn-0.05Mg-0.05Ca alloy with bimodal grain structure is developed by extrusion and caliber rolling. The alloy's Ewh reaches as high as 11.6%, due to the hetero-deformation induced effect of bimodal grain structure. Additionally, micro-galvanic corrosion happens between bimodal grains, which accelerates the alloy's degradation. <em>In vitro</em> studies show that the alloy exhibits enhanced antibacterial activity, good cytocompatibility, and promising osteogenic effect, indicating that it is a promising candidate for orthopedic implants.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 584-603"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878914","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":"Assembly of a biomimetic copper-based nanocomplex for alleviating hypoxia to enhance cuproptosis against osteosarcoma and lung metastasis","authors":"Junyong Wu ,&nbsp;Xinyan Hao ,&nbsp;Lin Qi ,&nbsp;Wenjie Xu ,&nbsp;Chi Yin ,&nbsp;Yucheng Tang ,&nbsp;Pengcheng Sun ,&nbsp;Dehua Liao ,&nbsp;Xiongbin Hu ,&nbsp;Tiantian Tang ,&nbsp;Chao Tu ,&nbsp;Daxiong Xiang ,&nbsp;Zhihong Li","doi":"10.1016/j.actbio.2024.12.049","DOIUrl":"10.1016/j.actbio.2024.12.049","url":null,"abstract":"<div><div>Osteosarcoma tissues demonstrated elevated expression of proteins (FDX1 and DLAT) integral to cuproptosis in our preliminary study, indicating the potential effectiveness of anti-tumor strategies predicated on this process. Nevertheless, the overexpression of copper export proteins and the challenge of copper ion penetration may contribute to insufficient local copper ion concentration for inducing cuproptosis. Herein, we engineered a biomimetic copper-elesclomol-polyphenol network for the efficient delivery of copper ions and the copper ionophore elesclomol. Simultaneously, we integrated catalase (CAT) to alleviate tumor hypoxia, thereby inducing a greater reliance of tumor cells on aerobic respiration and enhancing cuproptosis sensitivity. In vitro analyses revealed that the nanocomplex exhibited potent cytotoxicity and displayed hallmark characteristics of cuproptosis. In vivo trials further validated targeted tumor accumulation, resulting in the suppression of tumor growth and lung metastasis. An augmentation in the proportion of activated immune cells in both tumor and draining lymph nodes was observed. The improvement of immunosuppressive microenvironment facilitated a synergistic antitumor effect with cuproptosis. The therapeutic efficacy was further evidenced in two osteosarcoma models, highlighting the potential as a safe and effective strategy against osteosarcoma and lung metastasis.</div></div><div><h3>Statement of significance</h3><div>Osteosarcoma tissues exhibit a marked increase in the expression of proteins FDX1 and DLAT, which are crucial for cuproptosis. Moreover, cells that depend on mitochondrial respiration are more susceptible to cuproptosis. Here we developed a biomimetic copper-based nanocomplex to trigger cuproptosis against osteosarcoma and lung metastases. The nanocomplex demonstrated excellent biocompatibility and tumor targeting. Catalase incorporating facilitated oxygen generation within tumor microenvironment and alleviated hypoxia, thereby inducing a greater reliance of tumor cells on aerobic respiration and enhancing cuproptosis sensitivity. Simultaneously, the released Cu-elesclomol complexes induced proteotoxic stress responses and efficiently elicited cuproptosis, leading to increased release of proinflammatory factors and triggering anti-tumor immune activation. Our strategy holds promise for osteosarcoma treatment by inducing cuproptosis and achieving potent tumor suppression.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 348-361"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878929","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":"Corrigendum to “A composite hydrogel with co-delivery of antimicrobial peptides and platelet-rich plasma to enhance healing of infected wounds in diabetes” [Acta Biomaterialia 2021, 124, 205-218]","authors":"Shikun Wei ,&nbsp;Pengcheng Xu ,&nbsp;Zexin Yao ,&nbsp;Xiao Cui ,&nbsp;Xiaoxuan Lei ,&nbsp;Linlin Li ,&nbsp;Yunqing Dong ,&nbsp;Weidong Zhu ,&nbsp;Rui Guo ,&nbsp;Biao Cheng","doi":"10.1016/j.actbio.2024.11.030","DOIUrl":"10.1016/j.actbio.2024.11.030","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 632-636"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741605","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":"Corrigendum to “Vascular Endothelial Growth Factor-Capturing Aligned Electrospun Polycaprolactone/Gelatin Nanofibers Promote Patellar Ligament Regeneration” [Acta Biomaterialia 140, 2022, 122-246]","authors":"Zhengchao Yuan ,&nbsp;Dandan Sheng ,&nbsp;Liping Jiang ,&nbsp;Muhammad Shafiq ,&nbsp;AttaRehman ur Khan ,&nbsp;Rashida Hashim ,&nbsp;Yujie Chen ,&nbsp;Baojie Li ,&nbsp;Xianrui Xie ,&nbsp;Jun Chen ,&nbsp;Yosry Morsi ,&nbsp;Xiumei Mo ,&nbsp;Shiyi Chen","doi":"10.1016/j.actbio.2024.11.031","DOIUrl":"10.1016/j.actbio.2024.11.031","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 637-638"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756012","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":"Downregulation of the PI3K/AKT/mTOR/MMP-13 pathway for promoting interface healing via lubricating microspheres","authors":"Shiyi Yao ,&nbsp;Hui Yuan ,&nbsp;Luqi Yang ,&nbsp;Yin Zhang ,&nbsp;Hanyu Wang ,&nbsp;Renxuan Li ,&nbsp;Tingjun Ye ,&nbsp;Wenguo Cui ,&nbsp;Lei Wang","doi":"10.1016/j.actbio.2025.01.001","DOIUrl":"10.1016/j.actbio.2025.01.001","url":null,"abstract":"<div><div>Interface friction impedes tissue healing and stimulates interface cells to produce matrix metalloproteinases (MMPs); however, the precise mechanisms underlying matrix degradation, and the formation of fibrous scars remain unclear. This research involved the development of interface lubricating microspheres that inhibit the PI3K/AKT/mTOR signaling pathway in tenocytes. This inhibition significantly decreased MMP-13 expression and increased COL-1 production, thereby facilitating interface repair and regeneration. In vitro experiments demonstrated that interface friction activates the PI3K/AKT/mTOR/MMP-13 signaling pathway, while the use of interface lubricating microspheres reduced friction by 78 %, resulting in a threefold decrease in MMP-13 expression through pathway inhibition. Animal studies showed that the application of interface lubricating microspheres reduced friction at the tendon-bone interface, mitigating MMP-13-mediated matrix degradation and effectively reducing fibrous scar formation (as evidenced by decreased α-SMA expression), thus promoting interface healing following ACLR surgery in rats. Consequently, this study suggests that interface friction can trigger the PI3K/AKT/mTOR signaling pathway in tenocytes, leading to increased MMP-13 expression, matrix degradation, and fibrous scar formation. The use of interface lubricating microspheres can enhance interface healing by inhibiting this pathway, offering strategies for improving interface healing and minimizing fibrous scar formation.</div></div><div><h3>Statement of significance</h3><div>Interface healing plays a crucial role following tendon-bone surgeries, yet it is often hindered by challenges such as interface friction and scar formation. In this study, we propose a combined approach in which lubricating microspheres and an anti-matrix degradation drug are used to enhance interface healing. We fabricated novel lubricating microspheres that exhibit outstanding biocompatibility and degradability; these microspheres serve as lubricants for the tendon-bone interface and facilitate the delivery of doxycycline to reduce excessive matrix metalloproteinase (MMP) secretion. The experimental results demonstrated that this method could enhance tendon-bone interface healing in rats, resulting in increased bone formation and higher histological scores than those of the control group. This study represents a preliminary effort to integrate lubrication and anti-matrix degradation in interface healing, potentially offering new insights into the mechanism between interface friction and fibrous scar healing, while promoting interface healing by reducing interfacial friction.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 291-304"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960103","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 bioprinting approaches for enhancing stem cell-based neural tissue regeneration","authors":"Cemile Kilic Bektas,&nbsp;Jeffrey Luo,&nbsp;Brian Conley,&nbsp;Kim-Phuong N. Le,&nbsp;Ki-Bum Lee","doi":"10.1016/j.actbio.2025.01.006","DOIUrl":"10.1016/j.actbio.2025.01.006","url":null,"abstract":"<div><div>Three-dimensional (3D) bioprinting holds immense promise for advancing stem cell research and developing novel therapeutic strategies in the field of neural tissue engineering and disease modeling. This paper critically analyzes recent breakthroughs in 3D bioprinting, specifically focusing on its application in these areas. We comprehensively explore the advantages and limitations of various 3D printing methods, the selection and formulation of bioink materials tailored for neural stem cells, and the incorporation of nanomaterials with dual functionality, enhancing the bioprinting process and promoting neurogenesis pathways. Furthermore, the paper reviews the diverse range of stem cells employed in neural bioprinting research, discussing their potential applications and associated challenges. We also introduce the emerging field of 4D bioprinting, highlighting current efforts to develop time-responsive constructs that improve the integration and functionality of bioprinted neural tissues.</div><div>In short, this manuscript aims to provide a comprehensive understanding of this rapidly evolving field. It underscores the transformative potential of 3D and 4D bioprinting technologies in revolutionizing stem cell research and paving the way for novel therapeutic solutions for neurological disorders and injuries, ultimately contributing significantly to the advancement of regenerative medicine.</div></div><div><h3>Statement of significance</h3><div>This comprehensive review critically examines the current bioprinting research landscape, highlighting efforts to overcome key limitations in printing technologies—improving cell viability post-printing, enhancing resolution, and optimizing cross-linking efficiencies. The continuous refinement of material compositions aims to control the spatiotemporal delivery of therapeutic agents, ensuring better integration of transplanted cells with host tissues.</div><div>Specifically, the review focuses on groundbreaking advancements in neural tissue engineering. The development of next-generation bioinks, hydrogels, and scaffolds specifically designed for neural regeneration complexities holds the potential to revolutionize treatments for debilitating neural conditions, especially when nanotechnologies are being incorporated. This review offers the readers both a comprehensive analysis of current breakthroughs and an insightful perspective on the future trajectory of neural tissue engineering.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 20-48"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967418","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":"Interpenetrating networks of fibrillar and amorphous collagen promote cell spreading and hydrogel stability","authors":"Lucia G. Brunel ,&nbsp;Chris M. Long ,&nbsp;Fotis Christakopoulos ,&nbsp;Betty Cai ,&nbsp;Patrik K. Johansson ,&nbsp;Diya Singhal ,&nbsp;Annika Enejder ,&nbsp;David Myung ,&nbsp;Sarah C. Heilshorn","doi":"10.1016/j.actbio.2025.01.009","DOIUrl":"10.1016/j.actbio.2025.01.009","url":null,"abstract":"<div><div>Hydrogels composed of collagen, the most abundant protein in the human body, are widely used as scaffolds for tissue engineering due to their ability to support cellular activity. However, collagen hydrogels with encapsulated cells often experience bulk contraction due to cell-generated forces, and conventional strategies to mitigate this undesired deformation often compromise either the fibrillar microstructure or cytocompatibility of the collagen. To support the spreading of encapsulated cells while preserving the structural integrity of the gels, we present an interpenetrating network (IPN) of two distinct collagen networks with different crosslinking mechanisms and microstructures. First, a physically self-assembled collagen network preserves the fibrillar microstructure and enables the spreading of encapsulated human corneal mesenchymal stromal cells. Second, an amorphous collagen network covalently crosslinked with bioorthogonal chemistry fills the voids between fibrils and stabilizes the gel against cell-induced contraction. This collagen IPN balances the biofunctionality of natural collagen with the stability of covalently crosslinked, engineered polymers. Taken together, these data represent a new avenue for maintaining both the fiber-induced spreading of cells and the structural integrity of collagen hydrogels by leveraging an IPN of fibrillar and amorphous collagen networks.</div></div><div><h3>Statement of Significance</h3><div>Collagen hydrogels are widely used as scaffolds for tissue engineering due to their support of cellular activity. However, collagen hydrogels often undergo undesired changes in size and shape due to cell-generated forces, and conventional strategies to mitigate this deformation typically compromise either the fibrillar microstructure or cytocompatibility of the collagen. In this study, we introduce an innovative interpenetrating network (IPN) that combines physically self-assembled, fibrillar collagen—ideal for promoting cell adhesion and spreading—with covalently crosslinked, amorphous collagen—ideal for enhancing bulk hydrogel stability. Our IPN design maintains the native fibrillar structure of collagen while significantly improving resistance against cell-induced contraction, providing a promising solution to enhance the performance and reliability of collagen hydrogels for tissue engineering applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 128-142"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973639","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":"Broad-spectrum downregulation of inflammatory cytokines by polydopamine nanoparticles to protect the injured spinal cord","authors":"Dongdong Jiang ,&nbsp;Yaping Ding ,&nbsp;Shuai Hu ,&nbsp;Guangfei Wei ,&nbsp;Claudia Trujillo ,&nbsp;Zhiyuan Yang ,&nbsp;Zhenyang Wei ,&nbsp;Wei Li ,&nbsp;Dongfei Liu ,&nbsp;Cong Li ,&nbsp;Wenwu Gan ,&nbsp;Hélder A. Santos ,&nbsp;Guoyong Yin ,&nbsp;Jin Fan","doi":"10.1016/j.actbio.2024.12.028","DOIUrl":"10.1016/j.actbio.2024.12.028","url":null,"abstract":"<div><div>Acute neuroinflammation, which is notably characterized by a significant elevation in pro-inflammatory cytokines and chemokines, often rapidly develops following a traumatic spinal cord injury and exacerbates damage in the lesion area. This study addresses the limitations inherent in strategies that regulate only a single or a few cytokines, which are often insufficient to counteract the progression of secondary injuries. We explore the use of polydopamine nanoparticles as a broad-spectrum immunomodulator, capable of capturing by adsorption a wide range of cytokines and thereby effectively suppressing neuroinflammation. Leveraging their adhesive properties, these nanoparticles promptly reduce levels of various excessive cytokines, including IL-1α, IL-1β, IL-6, IL-10, IL-17A, IL-18, TNF-α, MCP-1, GRO/KC, M-CSF, MIP-3α, and IFN-γ, primarily through physical adsorption. This reduction in cytokine levels contributes to the subsequent inhibition of pro-inflammatory M1 microglia and A1 astrocyte activation, aiding in the recovery of motor functions <em>in vivo</em>. In summary, polydopamine nanoparticles represent a versatile and effective approach for modulating acute neuroinflammation in spinal cord injuries. By broadly down-regulating cytokines, polydopamine nanoparticles propose an innovative approach for treating spinal cord injuries.</div></div><div><h3>Statement of significance</h3><div>The current study demonstrated the immunomodulatory potential of polydopamine nanoparticles in mitigating neuroinflammation following spinal cord injury. Both <em>in vitro</em> and <em>in vivo</em> analyses revealed significant downregulation of several key cytokines among a panel of 23 cytokines and chemokines. The potential underlying mechanisms governing these interactions were elucidated through comprehensive molecular dynamics simulations for the first time. Consequently, the downregulation of these cytokines and chemokines led to the inhibition of pro-inflammatory M1 microglia and A1 astrocyte activation in both <em>in vitro</em> and <em>in vivo</em> models. This inhibition protected neurons within the microenvironment, resulting in improved locomotor functions. Overall, this study underscores the prominent therapeutic efficacy of polydopamine nanoparticles in alleviating neuroinflammation, highlighting their potential as broad-spectrum regulators in intricate microenvironments.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 559-570"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}