Acta Biomaterialia最新文献

{"title":"Bioactive glass-induced B cell depletion remodels the osteoimmunological microenvironment to enhance osteogenesis","authors":"Yue Chen ,&nbsp;Ting Wang ,&nbsp;Ziwei Yan ,&nbsp;Fanrui Zeng ,&nbsp;Yingyi Li ,&nbsp;Chen Bao ,&nbsp;Hua Wang ,&nbsp;Usanee Pantulap ,&nbsp;Aldo R. Boccaccini ,&nbsp;Kai Zheng ,&nbsp;Wen Sun","doi":"10.1016/j.actbio.2025.06.001","DOIUrl":"10.1016/j.actbio.2025.06.001","url":null,"abstract":"<div><div>B cells are critical in bone homeostasis, and their dysfunction is linked to various bone disorders. Bioactive glasses (BGs) are known for their immunomodulatory properties and are increasingly utilized in bone regeneration. However, the specific effects of BGs on B cells and their subsequent impact on osteogenesis remain unclear. In this study, we investigated the immunomodulatory effects of three BGs (45S5-BG, 13-93-BG, and B3-Cu-Zn-BG) on B cells. 13-93-BG had minimal effect on the survival of activated B cells, while 45S5-BG induced a noticeable cytotoxic effect on B cells. Notably, B3-Cu-Zn-BG exhibited the highest cytotoxicity towards pathogenic B cells, prompting further investigation into its mechanisms. The ionic dissolution products (IDPs) of B3-Cu-Zn-BG exerted concentration- and time-dependent cytotoxicity on B cells by upregulating the expression of genes associated with the mitochondrial apoptosis pathway and NADPH oxidases. B3-Cu-Zn-BG-derived IDPs elevated reactive oxygen species production in B cells, which induced apoptosis in a concentration-dependent manner. Additionally, when co-cultured with bone marrow stem cells (BMSCs), B3-Cu-Zn-BG-derived IDPs promoted osteoblastic differentiation of BMSCs while selectively targeting and eliminating B cells. To confirm the <em>in vivo</em> osteoimmunomodulatory effects of B3-Cu-Zn-BG-derived IDPs, we employed a human tumor necrosis factor transgenic (TNF-tg) mouse model of rheumatoid arthritis. Intra-articular injection of the IDPs in TNF-tg arthritic mice attenuated bone erosion by reducing B cell aggregates and improving osteoblastic differentiation. This study indicates that B3-Cu-Zn-BG not only induces B cell apoptosis but also promotes osteogenesis, highlighting its potential as a therapeutic strategy for inflammatory bone diseases.</div></div><div><h3>Statement of significance</h3><div>Despite decades of use in tissue regeneration, bioactive glasses (BGs) have not been thoroughly evaluated for their immunomodulatory effects. B cells play a crucial role in the pathogenesis of numerous inflammatory bone diseases. By investigating the immunomodulatory properties of B3-Cu-Zn-BG, this research reveals its ability to selectively induce B cell apoptosis and promote osteoblastic differentiation of bone marrow stem cells. Notably, in a rheumatoid arthritis mouse model, B3-Cu-Zn-BG significantly reduced bone erosion and enhanced osteogenesis. BGs of specific compositions have thus great potential in regulating the osteoimmunology microenvironment by locally modulating B cells. These findings underscore the potential of BGs as a novel therapeutic approach for inflammatory bone diseases, offering insights into bone regeneration and immunomodulation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 648-664"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236205","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":"Fine-tuning of material properties by catch bonds","authors":"Md Foysal Rabbi ,&nbsp;Gijsje H. Koenderink ,&nbsp;Yuval Mulla ,&nbsp;Taeyoon Kim","doi":"10.1016/j.actbio.2025.06.004","DOIUrl":"10.1016/j.actbio.2025.06.004","url":null,"abstract":"<div><div>Semiflexible polymer networks are ubiquitous in biological systems, including a scaffolding structure within cells called the actin cytoskeleton. The polymers in these networks are interconnected by transient bonds. For example, actin filaments in the cytoskeleton are physically connected via cross-linker proteins. The mechanical and kinetic properties of the cross-linkers significantly affect the rheological properties of the actin cytoskeleton. Here, we employed an agent-based model to elucidate how the force-dependent behaviors of the cross-linkers determine the material properties of passive networks without molecular motors and the force generation of active networks with molecular motors. The cross-linkers are assumed to behave either as a slip bond, whose dissociation rate increases with forces, or as a catch-slip bond, whose dissociation rate decreases with forces at low force level but increases with forces at high force level. We found that catch-slip-bond cross-linkers can simultaneously increase both the stress and the strain at the yield point. Through a systematic variation in the force dependence of the catch-slip bonds, we identified the specific parameter regimes that enable network reinforcement and enhanced extensibility simultaneously. Specifically, we found that a sufficiently large force threshold for the catch-slip transition is essential for maintaining dynamic force-bearing elements that turnover continuously—a mechanism not achievable with slip bonds. Additionally, we demonstrate that such force-dependent redistribution of the catch-slip bonds substantially enhances internal contractile forces generated by a motor in active networks.</div></div><div><h3>Statement of significance</h3><div>Polymer networks are ubiquitous in industrial and biological systems. The polymers in these networks are often interconnected by transient bonds. The transient bonds behave as a slip bond whose dissociation rate is proportional to forces or as a catch-slip bond whose dissociation rate decreases with increased force (catch) at low force level but increases with increased force (slip) at high force level. In this study, we computationally tested different types of catch-slip bonds to define how the material properties of polymer networks are fine-tuned by each property of molecular bonds. We found that catch-slip bonds can increase both stress and strain at a yield point, which is impossible to achieve without the catch-slip bonds.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 372-384"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236206","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":"Biodegradable Zn-xY alloys with enhanced osteogenesis and angiogenesis effects for bone implant applications","authors":"Shimin Liang ,&nbsp;Shaokang Du ,&nbsp;Yufeng Zheng ,&nbsp;Dandan Xia ,&nbsp;Yongsheng Zhou","doi":"10.1016/j.actbio.2025.05.048","DOIUrl":"10.1016/j.actbio.2025.05.048","url":null,"abstract":"<div><div>Biodegradable zinc-based alloys have gained significant attention in the biomedical field due to their favorable degradability, but challenges remain in enhancing their mechanical properties and biocompatibility. As promising candidates for bone implant materials, improving osteogenic differentiation, angiogenesis and antibacterial properties is crucial. In this study, Zinc-xYttrium (Zn-xY, <em>x</em> = 0.1, 0.6, 1.0 and 2.0 at.%) alloys were developed, and their mechanical properties, degradation behavior, cytocompatibility, osteogenic activity, angiogenic potential and antibacterial properties were systematically evaluated. Specifically, Zn-2.0Y exhibited the highest mechanical strength, with a tensile strength (UTS) of 230 MPa, yield strength (YS) of 170 MPa, and elongation at break (ER) of approximately 16%. In terms of degradation, Zn-2.0Y demonstrated the slowest degradation rate. Additionally, this alloy significantly enhanced osteogenic differentiation and mineralization of human bone marrow-derived mesenchymal stem cells (hBMSCs) and promoted migration and angiogenic activity in human umbilical vein endothelial cells (HUVECs). Moreover, this alloy demonstrated far better antibacterial properties than pure Zn. <em>In vivo</em> rat femoral implantation studies further confirmed that Zn-2.0Y promoted bone integration. Moreover, the study revealed and validated that Zn-2.0Y enhances osteogenic and angiogenic activities through the PI3K/AKT signaling pathway. These findings highlight Zn-2.0Y as a promising biodegradable material for bone implant applications.</div></div><div><h3>Statement of significance</h3><div>The development of advanced biodegradable bone implant materials is crucial for addressing complex challenges in bone repair. This study investigates Zinc-xYttrium (Zn-xY, <em>x</em> = 0.1, 0.6, 1.0 and 2.0 at.%) alloys, focusing on Zn-2.0Y, which exhibits tensile strength &gt;230 MPa, yield strength ∼170 MPa, and elongation at break ∼16%. The degradation rate of Zn-xY alloys decreases with increasing Y content, with Zn-2.0Y showing the lowest rate of 45 µm/y. <em>In vitro</em> and <em>in vivo</em> studies demonstrate that Zn-2.0Y promotes osteogenesis and angiogenesis by activating the PI3K/AKT signaling pathway. These findings highlight Zn-2.0Y as a promising biodegradable material for bone repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 684-702"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251265","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":"The foreign body response to biomaterial implants is reduced by co-inhibition of TLR2 and TLR4","authors":"Brittany J. Thompson ,&nbsp;Emma L. Carillion ,&nbsp;Scott Alper ,&nbsp;Stephanie J. Bryant","doi":"10.1016/j.actbio.2025.06.020","DOIUrl":"10.1016/j.actbio.2025.06.020","url":null,"abstract":"<div><div>The foreign body response (FBR) is a formidable reaction that occurs to any non-biological implantable biomaterial and results in fibrous encapsulation. Non-specific protein adsorption is the first stage of the FBR and is thought to initiate the response by activation of innate immune cells. Here we show that Toll-like receptors (TLRs) 2 and 4 are the primary receptors responsible for recognizing surface adsorbed proteins as damage associated molecular patterns (DAMPs) and they determine the material dependent FBR. An <em>in vitro</em> model using multiple biomaterials identified that macrophages, not neutrophils, respond to surface-adsorbed plasma via TLR2 and/or TLR4 and that deletion of both was required to inhibit activation across all materials. In the more complex <em>in vivo</em> environment, simultaneous deletion of TLR2 and TLR4 nearly abrogated the FBR to multiple biomaterials and eliminated the material dependencies in a subcutaneous implant mouse model. Deletion of either TLR2 or TLR4 showed either no effect or a partial reduction, depending on the material, demonstrating that TLRs determine the material-dependent FBR <em>in vivo</em>. Collectively, we identified TLR2 and TLR4 as necessary receptors for the FBR and implicate macrophage recognition of DAMPs of surface-adsorbed proteins, which vary depending on the material, as the main driver initiating the FBR. Our findings establish TLR2 and TLR4 as therapeutic targets to evade the FBR across a range of implantable materials.</div></div><div><h3>Statement of significance</h3><div>Synthetic biomaterials when implanted elicit a foreign body response (FBR) leading to fibrous encapsulation. The mechanisms however are not fully understood. When a biomaterial is implanted, proteins non-specifically adsorb to the material. These proteins may act as damaged associated molecular patterns (DAMPs) to induce inflammation. Toll like receptor (TLR) 2 and 4 are known receptors that recognize DAMPs. This work investigated several different biomaterials and found that TLR2 and TLR4 mediate the FBR in a material-dependent manner. Deleting both TLR2 and TLR4 was necessary to inhibit significantly fibrous capsule formation across all materials tested. Our findings provide direct evidence that DAMPs are the main driver of the FBR and establish TLR2/4 as potential therapeutic targets to evade the FBR.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 320-335"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295482","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":"Microindentation reveals softening of the equatorial and anterior sclera during early myopia development in tree shrew eyes","authors":"Xuesong Zhang ,&nbsp;Mustapha El Hamdaoui ,&nbsp;Seongjin Lim ,&nbsp;Rafael Grytz ,&nbsp;Johannes Weickenmeier","doi":"10.1016/j.actbio.2025.05.064","DOIUrl":"10.1016/j.actbio.2025.05.064","url":null,"abstract":"<div><div>Myopia has reached epidemic levels worldwide and significantly increases the risk for blinding diseases such as glaucoma, making it a pressing global health concern. Myopia is commonly associated with biomechanical weakening and remodeling of the sclera, resulting in an excessively elongated eye relative to its optical system. The exact regions of scleral remodeling and tissue softening remain unclear. The purpose of this study was to establish a microindentation testing approach for spatial mapping of scleral stiffness and localization of softened regions. Microindentation tests were performed across entire flat-mounted scleral samples obtained from juvenile tree shrews with either normal visual experience or four days of monocular -5 D lens treatment to induce myopia in one eye, whereas the other eye served as control. Inverse finite element analyses were performed to estimate the apparent modulus at each indentation location, while accounting for large deformations. The generated stiffness maps revealed that scleral stiffness increased with distance from the posterior pole. Compared to normal and control eyes, scleral stiffness was significantly reduced in myopic eyes at the equatorial and anterior scleral regions, but not at the posterior pole. This result was surprising because the posterior pole has previously been regarded as the primary site of scleral remodeling and biomechanical weakening in myopia. Regions that exhibited significant changes in stiffness were also identified as the thinnest scleral regions, suggesting that scleral softening in myopia begins in regions that are most vulnerable to excessive stretching. It remains unclear whether scleral softening at the equatorial and anterior regions during early stages of myopia development is a precursor of biomechanical weakening of the sclera as myopia progresses. This study introduces an indentation-based approach to map scleral stiffness across the entire sclera of tree shrew eyes thus providing higher spatial resolution compared to previous work. This novel approach provides insights into how and where myopic changes may begin, highlighting potential targets for early interventions, such as scleral crosslinking, at structurally vulnerable regions.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 446-456"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303867","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":"Co-assembly of oligo-urethane nanoparticles with defined lipid additives to tailor RNA delivery into cells","authors":"Suja Shrestha ,&nbsp;Elaine Yan ,&nbsp;Beining Yang ,&nbsp;Aled Blundell ,&nbsp;Allen C.T. Teng ,&nbsp;Ryan M. Marks ,&nbsp;Ronald Cohn ,&nbsp;Evgueni Ivakine ,&nbsp;Anthony O. Gramolini ,&nbsp;J.Paul Santerre","doi":"10.1016/j.actbio.2025.06.017","DOIUrl":"10.1016/j.actbio.2025.06.017","url":null,"abstract":"<div><div>Developing safe and effective biomaterials to deliver RNA into cells has grown in importance over recent years and has enabled the clinical translation of several gene therapies. Self-assembled oligo-urethane nanoparticles (PNPs) have several advantageous properties, such as (1) mitigating immune cell response in vivo, (2) low cytotoxicity in a broad range of cells, and (3) capable of delivering oligonucleotides or proteins into cells. Here, we were interested in defining unique configurations of PNPs to assess their relative cytotoxicity to human cells, comparing them to a popular commercial lipid system MessengerMax, as some cationic lipids have been found to have associated toxicity, instigating the search for less toxic counterparts. This was then followed by demonstrating the ability of enhanced green fluorescent protein (EGFP) mRNA to be loaded onto the PNPs, and to establish methods to enable the efficient transgene expression in a number of cell types, including Caco-2 and C₂C₁₂ cells which are known to be difficult-to-transfect cells. The addition of small amounts of PEGylated lipid to PNP significantly increased EGFP expression in HEK293T cells, Caco-2 cells and C₂C₁₂ cells at an effective mRNA/PNPs ratio (wt/wt) of 1:40, while the addition of the ionizable cationic lipid, significantly increased EGFP expression in C₂C₁₂ cells and differentiated C₂C₁₂ cells (myofibers) at mRNA/PNPs ratio (wt/wt) of 1:125, while keeping PNPs mass constant to 62.5 μg and changing the mRNA mass. Our study demonstrated that lipid-assisted, PNP-mediated mRNA delivery achieved a high transfection efficiency in terminally differentiated myofibers, paving the way for potential innovative therapeutics, e.g. targeted to muscular dystrophies.</div></div><div><h3>Statement of significance</h3><div>There are reports of diverse delivery agents for RNA, but there is still unmet need for more versatile, and safe delivery vehicles. In this study we demonstrated that when compared to MessengerMax (a lipid-based mRNA transfection reagent), self-assembled oligo-urethane nanoparticle (PNP) showed favorable cell viability. The scope of PNP as a RNA delivery vehicle was extended beyond HEK293T cells by showing transfections into a number of cell types. The addition of select lipids to PNPs, significantly increased EGFP expression in difficult-to-transfect cells: Caco-2 (2.9-fold), C₂C₁₂ (1.4-fold) and differentiated C₂C₁₂ (1.28-fold) cells when compared to PNPs. These findings indicate that select lipid incorporation on PNPs provide a promising strategy to improve the efficacy of RNA therapeutics for diseases in clinical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 457-470"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310928","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 “Nanoengineered injectable hydrogels for wound healing application” [Acta Biomaterialia 2018, 70, 35-47]","authors":"Giriraj Lokhande ,&nbsp;James K. Carrow ,&nbsp;Teena Thakur ,&nbsp;Janet R. Xavier ,&nbsp;Madasamy Parani ,&nbsp;Kayla J. Bayless ,&nbsp;Akhilesh K. Gaharwar","doi":"10.1016/j.actbio.2025.05.005","DOIUrl":"10.1016/j.actbio.2025.05.005","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 707-708"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111507","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":"Recombinant cytokine bioconjugates with degradable nanogel substrates for macrophage immunotherapy","authors":"Rana Ajeeb ,&nbsp;Chloé Catelain ,&nbsp;Harsh A. Joshi ,&nbsp;Danuta Radyna ,&nbsp;John R. Clegg","doi":"10.1016/j.actbio.2025.05.066","DOIUrl":"10.1016/j.actbio.2025.05.066","url":null,"abstract":"<div><div>Cytokines are potent endogenous modulators of innate immunity, making them key mediators of macrophage plasticity for immunotherapy. However, the clinical translation of recombinant cytokines as therapeutics is limited by systemic side effects, caused by cytokines’ pleiotropy, potency, and non-specific biodistribution following systemic dosing. We developed a cytokine delivery platform utilizing poly(acrylamide-co-methacrylic acid) synthetic nanogels as a biodegradable substrate for conjugated recombinant cytokines (i.e., IFNγ, IL4, or IL10), called Synthetic Nano-CytoKines or “SyNK”. We evaluated the phenotypic response of macrophages to these conjugates following prophylactic or therapeutic dosing, in the presence or absence of soluble inflammatory signals. Our data confirmed that SyNK is highly cytocompatible with murine macrophages, preserves the activity of conjugated recombinant cytokines to both macrophages and dendritic cells, and minimizes systemic exposure to freely soluble recombinant cytokines. Intrinsic activity of the nanomaterial was modest, acting in combination with the conjugated cytokine, and resulted in unique phenotypes with IL4-SyNK and IL10-SyNK stimulation that could potentially be leveraged for therapeutic applications. We further demonstrated that RAW264.7 macrophages adopt distinct alternative phenotypes upon IL4 or IL10 stimulation in different classically polarizing microenvironments, as measured by spectral flow cytometry and secretome multiplex, which are similar for soluble recombinant cytokine and the corresponding SyNK. These findings offer a potential mechanism through which IL4 or IL10-SyNK can redirect the classically activated macrophage antigen presentation, T cell co-stimulation, or microenvironment regulatory functions for therapeutic purposes.</div></div><div><h3>Statement of significance</h3><div>Cytokines have been extensively investigated as immune therapies, but their clinical translation is limited by their systemic toxicity and frequent dosing regimens. Existing approaches have improved cytokine stability and local delivery but still face challenges in systemic administration and controlling immune response. We developed a cytokine delivery platform using biodegradable poly(acrylamide-co-methacrylic acid) nanogels to conjugate cytokines (e.g. IFNγ, IL4, or IL10) aimed at systemic macrophage immunotherapy. We show that our platform preserves cytokine activity and eliminates the release of free cytokine. We further explore, for the first time, how different stimuli in the macrophage environment influence their response to the cytokine bioconjugates. Our work provides thorough insights into macrophage plasticity and addresses key limitations of current strategies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 604-617"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192601","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":"Divergent effects of premineralization and prevascularization on osteogenesis and vascular integration in humanized tissue engineered bone constructs","authors":"Sugandha Bhatia ,&nbsp;Luke Hipwood ,&nbsp;Briony Claxton ,&nbsp;Agathe Bessot ,&nbsp;Angus Weekes ,&nbsp;Kamil Sokolowski ,&nbsp;Tomoji Mashimo ,&nbsp;Nathalie Bock ,&nbsp;Jacqui McGovern","doi":"10.1016/j.actbio.2025.06.019","DOIUrl":"10.1016/j.actbio.2025.06.019","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Osteogenesis (bone formation) and vascularization (blood vessel formation) are two central and interconnected physiological-relevant processes in bone formation. Prevascularization of humanized tissue-engineered bone constructs (hTEBCs) has been proposed to better mimic the human bone microenvironment by enhancing vascular integration and facilitating greater osteogenic capacity. Here, we investigated the effects of premineralization and prevascularization on bone and vasculature development in an ectopic hTEBC model using a scaffold-hydrogel composite approach. Human osteoblast cells (hOBs) were cultured under osteogenic conditions (OM), with or without a 3-day mineralization boost (OM+) period for 4 weeks prior to implantation &lt;em&gt;in vivo&lt;/em&gt; in a supporting porous polycaprolactone (mPCL) scaffold. Separately, photocrosslinkable fish gelatin-derived hydrogels placed within supporting mPCL scaffolds showed formation of elongated vascular networks as early as day 3 with &lt;em&gt;in vitro&lt;/em&gt; coculture of human umbilical vein endothelial cells (HUVECs) and human bone marrow mesenchymal stem/stromal cells (MSCs). The OM and OM+ cultured constructs were subcutaneously implanted into immunocompromised rats with and without the prevascular hydrogels, resulting in four subgroups: OM, OM+, OM/Vas, and OM+/Vas. Our results demonstrated that the OM+ group led to more rapid osteoinduction and enhanced osteogenic differentiation &lt;em&gt;in vivo&lt;/em&gt; with woven bone structure and active remodeling. Conversely, prevascularization (OM/Vas, OM+/Vas groups) led to reduce &lt;em&gt;in vivo&lt;/em&gt; bone volume and density but promoted the development of human endothelial networks and successful anastomosis with host vasculature. Our study highlights the distinct contributions of premineralization and prevascularization, where premineralization is critical for robust bone formation and prevascularization enhances vascular integration, providing important insights for advancing the physiological relevance of hTEBC models in animal hosts.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;This study demonstrates the development of humanized tissue engineered bone constructs incorporating a vascular niche using a rat. By integrating innovative premineralization and prevascularization techniques within scaffold-hydrogel composites, we show that premineralization accelerates bone formation, while prevascularization promotes endothelial network formation and integration with host vasculature. Photocrosslinkable, low-stiffness LunaGel™ hydrogels enhanced microcapillary-like structure formation and endothelial sprouting in &lt;em&gt;in vitro&lt;/em&gt; co-culture. However, by combining osteogenic and vascular cues within a biodegradable composite, this work advances the bone tissue engineering field by creating a model that more accurately reflects the divergent and competing nature of vascularization and bone formation. This platform has broad applicability for studying bone-vascular i","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 665-683"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295479","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":"A biomimetic nanofiber composite hydrogel with tissue adhesion, self-healing and antibacterial ability for infected wound healing","authors":"Yinghao Tian ,&nbsp;Xiaogang Bao ,&nbsp;Shunmin Wang ,&nbsp;Chen Tang ,&nbsp;Nianqi Wu ,&nbsp;Guifei Li ,&nbsp;Kaixuan Ren ,&nbsp;Jingbo Yin ,&nbsp;Shifeng Yan ,&nbsp;Guohua Xu","doi":"10.1016/j.actbio.2025.04.002","DOIUrl":"10.1016/j.actbio.2025.04.002","url":null,"abstract":"<div><div>Skin injuries represent a significant clinical challenge, as conventional dressings frequently induce secondary trauma and microbial infiltration due to suboptimal barrier properties, ultimately delaying tissue repair. Ideal wound dressings should not only replicate the structure of native skin tissue but also create an environment conducive to cell viability. In this study, an injectable nanofiber composite self-healing hydrogel was developed for treating infected wounds. The antimicrobial properties of the hydrogel were achieved through the adsorption of branched polyethyleneimine (PEI) on gelatin fibers, while its self-healing capabilities were enhanced via Schiff base reactions and its tissue adhesion was strengthened by the incorporation of dopamine. Results demonstrated that the hydrogel exhibited strong biocompatibility and antimicrobial activity, promoted macrophage polarization towards the M2 phenotype, effectively suppressed inflammation, and facilitated wound healing in an infected wound model.</div></div><div><h3>Statement of significance</h3><div>Wound infections pose a significant clinical challenge, often impeding healing and, in severe cases, leading to ulceration or life-threatening complications. In this study, a gelatin nanofiber composite hydrogel (PGF@ALG/PLGA hydrogel) functionalized with branched polyethyleneimine (PEI) was developed to address infected wounds through a biomimetic structure and enhanced pro-healing properties. The gelatin nanofibers within the hydrogel matrix facilitated electrostatic immobilization of PEI, effectively mitigating its inherent cytotoxicity by restricting free cationic charge exposure while ensuring localized surface enrichment. The resulting hydrogel exhibited robust tissue adhesion and autonomous self-healing capability. In infected wound models, the PEI-modified nanofibers within PGF@ALG/PLGA hydrogels demonstrated obvious antibacterial efficacy and promoted macrophage polarization to the M2 phenotype, synergistically accelerating the transition from the inflammatory phase to tissue regeneration. These findings underscore the therapeutic potential of PGF@ALG/PLGA hydrogel as a multifunctional platform for managing chronic infected wounds.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"200 ","pages":"Pages 326-339"},"PeriodicalIF":9.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788977","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}