Acta Biomaterialia最新文献

{"title":"Syngeneic adipose-derived stromal cells modulate the immune response but have limited persistence within decellularized adipose tissue implants in C57BL/6 mice","authors":"John T. Walker ,&nbsp;Tyler T. Cooper ,&nbsp;Joy Dunmore-Buyze ,&nbsp;Fiona E. Serack ,&nbsp;Courtney Brooks ,&nbsp;Aaron Grant ,&nbsp;Maria Drangova ,&nbsp;Gilles Lajoie ,&nbsp;Gregory A. Dekaban ,&nbsp;Lauren E. Flynn","doi":"10.1016/j.actbio.2025.02.015","DOIUrl":"10.1016/j.actbio.2025.02.015","url":null,"abstract":"<div><div>The delivery of adipose-derived stromal cells (ASCs) on cell-instructive decellularized adipose tissue (DAT) scaffolds is a promising strategy for stimulating host-derived soft tissue regeneration. However, a better understanding of the mechanisms through which ASCs modulate regeneration <em>in vivo</em> is needed to harness these cells more effectively. In this study, DAT scaffolds, both with and without seeded syngeneic DsRED⁺ mouse ASCs, were implanted into immunocompetent C57BL/6 mice. Downstream analyses focused on assessing donor ASC persistence and phenotype, as well as the effects of ASC seeding on host macrophage polarization and the perfused host vascular network. Notably, most donor ASCs were cleared from the scaffolds by 2 weeks. Mass spectrometry-based proteomics indicated that the transplanted ASCs maintained their pre-implantation phenotype up to 1 week <em>in vivo</em>, suggesting that the cells were not undergoing programmed cell death. A higher fraction of the infiltrating host macrophages expressed CD68 and Arginase-1 in the ASC-seeded implants up to 1-week post-implantation. Interestingly, a small population of phagocytic macrophages, identified by uptake of DsRED protein, was present in the DAT implants in the first 2 weeks and showed enhanced expression of CD68, Arginase-1, and CD163, along with reduced expression of iNOS. MicroCT angiography revealed a similar perfused vessel network in the seeded and unseeded groups at 4- and 8-weeks post-implantation. Overall, seeding with syngeneic ASCs modulated the host macrophage response to the DAT bioscaffolds at early timepoints, but did not impact long-term regenerative outcomes, potentially due to the rapid clearance of the donor cell population in this model.</div></div><div><h3>Statement of Significance</h3><div>Decellularized adipose tissue (DAT) is a promising biomaterial for treating soft tissue defects. Seeding with adipose-derived stromal cells (ASCs) can augment fat regeneration within DAT in pre-clinical models, but our understanding of how ASCs contribute to tissue regeneration <em>in vivo</em> remains limited. Furthermore, ASC clearance from implanted biomaterials is well described, but poorly understood. Here, ASC-seeded DAT was implanted subcutaneously in immunocompetent mice to assess how ASCs altered the host macrophage response, functional vascular regeneration, and long-term integration with the host tissues. Additionally, ASC phenotype and persistence were assessed to determine how these cells might be cleared from the implants. Such understanding is critical to design biomaterials that can better harness the therapeutic benefits of ASCs.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 169-182"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375114","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}

{"title":"Mechanistic insights into hydration-driven shape memory response in keratinous avian feather structures","authors":"Phani Saketh Dasika ,&nbsp;Yunlan Zhang ,&nbsp;Tarah N. Sullivan ,&nbsp;Sheron Tavares ,&nbsp;Marc A. Meyers ,&nbsp;Pablo D. Zavattieri","doi":"10.1016/j.actbio.2025.02.017","DOIUrl":"10.1016/j.actbio.2025.02.017","url":null,"abstract":"<div><div>Keratinous materials found in the feather shafts of flying birds possess impressive mechanical attributes, combining excellent strength-to-weight balance, toughness, and more. In this study, we investigate the shape memory effect in bird feather shafts, examining its underlying design principles as templates for bioinspired shape memory composites. Through analytical and computational analysis, we aim to uncover the underlying rules and design guidelines based on stimulus-induced softening (pertaining to strength and/or stiffness) and swelling (pertaining to expansion in volume). More specifically, we study a one-dimensional case to examine the synergistic relationship between the matrix and fibers inside the feather structure. We propose three distinct micro-mechanical modeling approaches to evaluate the contribution of each hydration-induced effect—softening, swelling, and the combined action of both. In all models, the matrix is considered to be an elastic-perfectly plastic material that is sensitive to hydration, while the fibers are treated as purely elastic and unaffected by hydration. The findings of the study provide informative insights into the nuanced nature of swelling within the material, highlighting that its desirability is dependent on specific conditions and circumstances. Furthermore, we find that the softening component plays a large pivotal role in driving the process of shape recovery. Using the proposed analytical framework and design principles, we develop a conceptual feather shaft-like composite, followed by demonstrating its tunability in degree of shape recovery and its versatility in selecting constituent base material components. This research offers valuable core framework for exploring and designing advanced bioinspired shape memory materials while eliminating the need for traditionally active shape memory components, holding promising potential for actuation, deployment, and morphing purposes.</div></div><div><h3>Statement of significance</h3><div>This study investigates the shape-memory effect in bird feather shafts, offering bioinspired strategies for designing advanced shape-memory composites. Unlike conventional materials, which often rely on external stimuli or active components, our research focuses on hydration-driven mechanisms–specifically, matrix softening and swelling. Through micro-mechanical modeling, we demonstrate that softening is the key driver of shape recovery, while swelling plays a secondary role under specific conditions. These insights provide new, passive design principles for creating tunable shape-memory composites without the need for traditional active components. The findings have broad implications for applications in actuation, morphing, and reconfigurable systems, where material adaptability is crucial.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 144-156"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384056","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":"Mitochondria-loading erythrocytes transfer mitochondria to ameliorate inflammatory bone loss","authors":"Shi Cheng ,&nbsp;Lu Zhou ,&nbsp;Wu-Yin Wang,&nbsp;Meng-Jie Zhang,&nbsp;Qi-Chao Yang,&nbsp;Wen- Da Wang,&nbsp;Kong-Huai Wang,&nbsp;Zhi-Jun Sun,&nbsp;Lu Zhang","doi":"10.1016/j.actbio.2025.02.024","DOIUrl":"10.1016/j.actbio.2025.02.024","url":null,"abstract":"<div><div>Inflammatory diseases frequently result in bone loss, a condition for which effective therapeutic interventions are lacking. Mitochondrial transfer and transplantation hold promise in tissue repair and disease treatments. However, the application of mitochondrial transfer in alleviating disorders has been limited due to its uncontrollable nature. Moreover, the key challenge in this field is maintaining the quality of isolated mitochondria (Mito), as dysfunctional Mito can exacerbate disease progression. Therefore, we employ Mito-loading erythrocytes (named MiLE) to achieve maintenance of mitochondrial quality. In addition, MiLE can be cryopreserved, allowing for long-term preservation of mitochondrial quality and facilitating the future application of mitochondrial transfer. In the inflammatory microenvironment, MiLE supplies Mito as well as O₂ to macrophages. By undergoing metabolic reprogramming, MiLE suppresses lipopolysaccharide-induced osteoclast differentiation and promotes macrophage polarization from M1 to M2 phenotype, ultimately ameliorating inflammatory bone destruction. In summary, this work tackles the challenges of uncontrollable mitochondrial transfer and mitochondrial quality maintenance, and offers an opportunity for future exploration of organelle transplantation.</div></div><div><h3>Statement of significance</h3><div>The application of mitochondrial transfer for the alleviation of pathologies has been hindered by the intrinsic limitations in terms of control and selectivity. Furthermore, maintaining mitochondrial integrity and functionality following isolation poses a significant challenge. In a pioneering approach, we develop a method for encapsulating mitochondria within erythrocytes, termed mitochondria-loading erythrocytes (MiLE), which ensures extended mitochondrial functionality and controlled transfer. Within an inflammatory microenvironment, MiLE supplies both mitochondria and O₂ to macrophages. By undergoing metabolic reprogramming, MiLE alleviates lipopolysaccharide-induced osteoclast differentiation and promotes macrophage polarization from M1 to M2 phenotype, ultimately ameliorating inflammatory bone destruction.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 225-239"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412073","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":"Electrospun meshes for abdominal wall hernia repair: Potential and challenges","authors":"Zhengni Liu ,&nbsp;Lei Liu ,&nbsp;Jiajie Liu ,&nbsp;Jinglei Wu ,&nbsp;Rui Tang ,&nbsp;Joy Wolfram","doi":"10.1016/j.actbio.2025.01.028","DOIUrl":"10.1016/j.actbio.2025.01.028","url":null,"abstract":"<div><div>Surgical meshes are widely used in abdominal wall hernia repairs. However, consensus on mesh treatment remains elusive due to varying repair outcomes, especially with the introduction of new meshes, posing a substantial challenge for surgeons. Addressing these issues requires communicating the features of emerging candidates with a focus on clinical considerations. Electrospinning is a versatile technique for producing meshes with biomechanical architectures that closely mimic the extracellular matrix and enable incorporation of bioactive and therapeutic agents into the interconnective porous network, providing a favorable milieu for tissue integration and remodeling. Although this promising technique has drawn considerable interest in mesh fabrication and functionalization, currently developed electrospun meshes have limitations in meeting clinical requirements for hernia repair. This review summarizes the advantages and limitations of meshes prepared through electrospinning based on biomechanical, biocompatible, and bioactive properties/functions, offering interdisciplinary insights into challenges and future directions toward clinical mesh-aided hernia repair.</div></div><div><h3>Statement of significance</h3><div>Consensus for hernia treatments using surgical meshes remains elusive based on varying repair outcomes, presenting significant challenges for researchers and surgeons. Differences in understanding mesh between specialists, particularly regarding material characteristics and clinical requirements, contribute to this issue. Electrospinning has been increasingly applied in mesh preparation through various approaches and strategies, aiming to improve abdominal wall hernia by restoring mechanical, morphological and functional integrity. However, there is no comprehensive overview of these emerging meshes regarding their features, functions, and clinical potentials, emphasizing the necessity of interdisciplinary discussions on this topic that build upon recent developments in electrospun mesh and provide insights from clinically practical prospectives.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 52-72"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017664","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}

{"title":"Copper-doped layered double hydroxides co-deliver proteins/drugs for cascaded chemodynamic/immunotherapy via dual regulation of tumor metabolism","authors":"Gaoming Li ,&nbsp;Zhiqiang Wang ,&nbsp;Yunqi Guo ,&nbsp;Cheng Ni ,&nbsp;Yue Gao ,&nbsp;Kaibing Xu ,&nbsp;Tingting Xiao ,&nbsp;Xiangyang Shi ,&nbsp;Mingwu Shen","doi":"10.1016/j.actbio.2025.02.008","DOIUrl":"10.1016/j.actbio.2025.02.008","url":null,"abstract":"<div><div>We report here a Cu²⁺-doped layered double hydroxide (LDH) nanoplatform to load both monocarboxylate transporter inhibitor diclofenac (DC) and lactate oxidase (LOX) for dual modulation of tumor lactate and redox metabolisms to activate immunotherapy through enhanced Cu-mediated chemodynamic therapy (CDT) of tumors. The formed LDH-DC-LOX nanoparticles with a diameter of 55 nm are stable, can be effectively taken up by cancer cells to regulate lactate through both LOX-mediated catalytic conversion and DC-enabled inhibition of extracellular efflux of lactate, and can exert redox metabolism through CDT <em>via</em> Cu²⁺-mediated glutathione (GSH) depletion and Fenton-like reaction with hydrogen peroxide (H₂O₂) that can be further accumulated <em>via</em> LOX-mediated catalysis. The major advantage of the developed LDH-DC-LOX nanoparticles lies in the therapeutic synergy and cascade that can be achieved through the loaded DC and LOX for enhanced tumor lactate metabolism regulation, for enhanced Cu-mediated CDT and redox metabolism regulation, and for activation of immunotherapy that can further enhances the Cu²⁺-mediated CDT effect. The developed LDH nanoplatform demonstrated here for effective murine breast tumor treatment provides a new paradigm for dual regulation of lactate and redox metabolisms that may enable synergistic and cascaded combination therapy of different cancer types.</div></div><div><h3>Statement of significance</h3><div>Targeting the tumor microenvironment (TME) to alter tumor metabolic pathways represents a promising strategy for next-generation cancer therapy. Herein, a copper-doped layered double hydroxide (LDH) nanoplatform is developed to co-deliver both diclofenac (DC) and lactate oxidase (LOX) to tumor cells for efficient dual regulation of tumor lactate and redox metabolisms, resulting in synergistic and cascaded chemodynamic therapy/immunotherapy of breast tumors. The developed LDH-DC-LOX nanoparticles can release Cu²⁺ and DC under an acidic TME, and can act in synergy to reduce TME lactate and generate H₂O₂, thus modulating redox metabolism and activating anticancer immunotherapy. The secreted cytokine IFN-γ after activation of antitumor immune responses can further mediate enhanced chemodynamic therapy effect through downregulation of cystine/glutamate transporter SLC7A11 to suppress GSH synthesis.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 350-362"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375106","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":"Photoswitching protein-XTEN fusions as injectable optoacoustic probes","authors":"Yishu Huang ,&nbsp;Mariia Stankevych ,&nbsp;Vipul Gujrati ,&nbsp;Uwe Klemm ,&nbsp;Azeem Mohammed ,&nbsp;David Wiesner ,&nbsp;Mara Saccomano ,&nbsp;Monica Tost ,&nbsp;Annette Feuchtinger ,&nbsp;Kanuj Mishra ,&nbsp;Oliver Bruns ,&nbsp;Arie Geerlof ,&nbsp;Vasilis Ntziachristos ,&nbsp;Andre C. Stiel","doi":"10.1016/j.actbio.2025.02.002","DOIUrl":"10.1016/j.actbio.2025.02.002","url":null,"abstract":"<div><div>Optoacoustic imaging (OAI) is a unique in vivo imaging technique combining deep tissue penetration with high resolution and molecular sensitivity. OAI relying on strong intrinsic contrast, such as blood hemoglobin, already shows its value in medical diagnostics. However, OAI sensitivity to current extrinsic contrast agents is insufficient and limits its role in detecting disease-related biomarkers. The recently introduced concept of photoswitching and temporal unmixing techniques for OAI allows detecting extrinsic contrast with high sensitivity, allowing the visualization of small populations of cells labeled with photoswitching proteins deep within the tissue. However, transgene modification might not be permitted in some cases, such as for diagnostic use. Therefore, it is desirable to leverage the concept of photoswitching OAI towards injectable formulations. Since photoswitchable synthetic dyes are mainly excited by blue wavelengths unsuited for imaging in tissue, we propose exploiting the addition of XTENs to photoswitching proteins towards yielding injectable agents. The addition of XTEN to a protein enhances its plasma half-life and bioavailability, thus allowing its use, for example, in targeted labeling approaches. In this pilot study, we show that intravenously injected near-infrared absorbing photoswitchable proteins, <em>Re</em>BphP-PCM, coupled to XTEN, allow highly sensitive optoacoustic visualization of a tumor xenograft in vivo. The sensitivity to XTENs-<em>Re</em>BphP-PCM determined by <em>ex vivo</em> analysis of labeled cells is one to two orders of magnitude beyond conventional synthetic dyes used currently in OAI. The enhanced sensitivity afforded by photoswitching OAI, in combination with the increased bioavailability and biocompatibility of XTENs-<em>Re</em>BphP-PCM, makes this fusion protein a promising tool for facilitating sensitive detection of biomarkers in OAI with a potential for future use in diagnostics.</div></div><div><h3>Statement of significance</h3><div>Optoacoustic imaging (OAI) is a unique in vivo imaging technique that combines deep tissue penetration with high resolution. OAI, which relies on intrinsic contrast, such as blood hemoglobin, could already be valuable in medical diagnostics. However, the use of extrinsic contrast agents to augment disease-related biomarkers in research and diagnostics suffers from very limited sensitivity of the generated contrast agent. We present an intravenously injected photoswitchable protein, <em>Re</em>BphP-PCM, coupled to XTEN, allowing highly sensitive OAI. The sensitivity is one to two orders of magnitude greater than that of conventional synthetic dyes used currently in OA imaging. The high sensitivity afforded by photoswitching together with the enhanced bioavailability and biocompatibility of the XTENs-<em>Re</em>BphP-PCM make this a standard agent for high-quality detection of OAI with potential for clinical use.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 536-546"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367029","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}

{"title":"Biodegradable ultrahigh-purity magnesium and its alloy ZX00 promote osteogenesis in the medullary cavity and glycogenolysis in the liver","authors":"Begüm Okutan ,&nbsp;Uwe Y. Schwarze ,&nbsp;Hansjörg Habisch ,&nbsp;Kamila Iskhakova ,&nbsp;Hanna Ćwieka ,&nbsp;Cláudia Ribeiro-Machado ,&nbsp;Julian P. Moosmann ,&nbsp;Clement Blanchet ,&nbsp;Iva Brcic ,&nbsp;Susana G. Santos ,&nbsp;Tobias Madl ,&nbsp;Berit Zeller-Plumhoff ,&nbsp;Annelie M. Weinberg ,&nbsp;D․C․Florian Wieland ,&nbsp;Nicole G. Sommer","doi":"10.1016/j.actbio.2025.02.007","DOIUrl":"10.1016/j.actbio.2025.02.007","url":null,"abstract":"<div><div>Magnesium (Mg)-based implants have become an attractive alternative to conventional permanent implants in the orthopedic field. While biocompatibility, degradation kinetics, and osseointegration of Mg-based implants have been mostly investigated, the impact of degradation products on bone remodeling and potential systemic effects remains unclear. The aim of this study was to evaluate the early and mid-term local and systemic tissue responses of degrading ultrahigh-purity ZX00 (Mg–Zn–Ca alloy) and ultrahigh-purity Mg (XHP-Mg) pins in a juvenile healthy rat model. The potential differences between implant types (degradable vs. permanent), implantation, and age-related changes were investigated using titanium (Ti), sham-operated, and control groups (non-intervention), respectively.</div><div>Degradation products of ZX00 and XHP-Mg pins promote osteogenesis in the medullary cavity by upregulating the expression levels of <em>Bmp2</em> and <em>Opg</em> within 14 days post-surgery. The higher degradation rate of XHP-Mg resulted in the accumulation of degradation products starting from day 3 and upregulation of different genes, particularly <em>Ccl2</em> and <em>Cepbp.</em> Besides good osseointegration and new bone tissue formation, we found a more parallel hydroxyapatite/collagen orientation along Mg-based pins in the perimeter region compared to Ti pins. In the liver, reduced glycogen levels in Mg-based pins indicated that degradation products promote glycogenolysis, while only the ZX00 group showed a higher serum glucagon level on day 14. Results suggest that degrading ZX00 and XHP-Mg pins stimulate osteogenesis mainly via <em>Bmp2</em> and <em>Opg</em> and promote glycogenolysis in the liver<em>,</em> while the higher degradation rate of XHP-Mg pins resulted in upregulation of different genes and metabolites.</div></div><div><h3>Statement of significance</h3><div>Bioresorbable magnesium (Mg)-based implants are promising alternative candidates for orthopedic interventions. Until now, a few <em>in vivo</em> studies explored how Mg-based implants promote osteogenesis in the medullary cavity and modulate systemic tissue responses. Herein, results demonstrate <em>i)</em> the degradation rate of the Mg-based implants has a crucial effect on osteogenesis via regulating <em>Bmp2</em> and <em>Opg</em> expression in the medullary cavity, <em>ii)</em> a parallel HAp/collagen matrix pattern in ZX00 and XHP-Mg groups compared to the Ti group, <em>iii)</em> both Mg pins promote glycogenolysis in the liver. Our findings highlight the dual role of Mg-based implants in bone remodeling and systemic metabolic modulation. Nevertheless, this is the first study to report the interaction between Mg-based implants and liver metabolism.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 599-613"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375105","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}

{"title":"Piezoelectric hydrogel with self-powered biomechanical stimulation enhances bone regeneration","authors":"Shuyan Zhang ,&nbsp;Lei Huang ,&nbsp;Weisin Chen ,&nbsp;Qi Chen ,&nbsp;Xin Liu ,&nbsp;Dihan Su ,&nbsp;Lan Xiao ,&nbsp;Dong Zhou ,&nbsp;Jian Zhang ,&nbsp;Libo Jiang ,&nbsp;Yulin Li","doi":"10.1016/j.actbio.2025.02.016","DOIUrl":"10.1016/j.actbio.2025.02.016","url":null,"abstract":"<div><div>Large bone defect healing remains a challenge in current clinical treatment, which suggests the need for functional bone repair materials. Piezoelectric materials can generate electrical stimulation under mechanical stress to improve the tissue healing environment, which are emerging candidates for tissue engineering. We created a self-powered piezoelectric hydrogel by simply blending the zinc oxide (ZnO) nanoparticles and regenerating silk fibroin (RSF). Our piezoelectric hydrogel showed controllable and suitable mechanical and piezoelectric properties which could generate electrical stimulation to promote bone tissue healing. Incorporating ZnO into RSF hydrogels not only enhanced their mechanical properties by 1.7 times and increased piezoelectric output by 2.8 times, but also mitigated the degradation rate. <em>In vitro</em> experiments showed that piezoelectric hydrogels significantly promoted osteogenesis differentiation of bone marrow mesenchymal stem cells (BMSCs) and enhanced vascular network reconstitution. <em>In vivo</em> experiments verified the osteogenic and angiogenic potential of ZnO/RSF piezoelectric hydrogels. ZnO/RSF piezoelectric hydrogel, a simple but universal strategy of RSF-based material to generate electric currents by body movement, provides novel insights into the applications of piezoelectric hydrogel.</div></div><div><h3>Statement of significance</h3><div>ZnO/RSF hydrogels with stable piezoelectric properties were prepared by doping ZnO, which can generate stable and continuous electrical signals under pressure. After implantation into the bone defect site, it can promote the osteogenic differentiation of bone marrow mesenchymal stem cells and improve the vasculogenic ability of human umbilical vein endothelial cells, thus promoting the healing of bone tissue.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 117-133"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384033","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":"Tailoring the dendronized structures of cyclodextrin-based supramolecular nanoassemblies for enhanced tumor paraptosis via disrupting endoplasmic reticulum homeostasis","authors":"Jiecheng Ji ,&nbsp;Jie Zhou ,&nbsp;Xue Li ,&nbsp;Yuxin Zhang ,&nbsp;Lei Gu ,&nbsp;Yujia Wang ,&nbsp;Xiuli Zheng ,&nbsp;Yunkun Li ,&nbsp;Jinhan He ,&nbsp;Cheng Yang ,&nbsp;Kai Xiao ,&nbsp;Qiyong Gong ,&nbsp;Chenjie Xu ,&nbsp;Kui Luo","doi":"10.1016/j.actbio.2025.02.009","DOIUrl":"10.1016/j.actbio.2025.02.009","url":null,"abstract":"<div><div>Bioactive nanomaterials have been extensively utilized in medical applications. There are, however, very few reports on clinical applications of methylated β-cyclodextrin-derived supramolecular bioactive nanoagents, particularly in relation to the chemical features and biological properties. Herein, we designed and fabricated supramolecular bioactive nanoassemblies derived from permethyl β-cyclodextrin (PMCD) with increased proportions of PMCD on their dendronized side chains and further investigated the impact of chemical structures on their antitumor efficacy. Importantly, enhanced antitumor efficacy was observed with an increase in the proportion of PMCD on the dendronized side chains. Notably, pHPMA-co-(dendron Permethyl-β-CD4) (P4), which was featured with the highest PMCD proportion on its side chains, demonstrated the greatest potency in disrupting endoplasmic reticulum (ER) homeostasis, thus achieving conspicuous tumor cell paraptosis and promising antitumor efficacy <em>in vivo</em> without obvious side effects. Mechanistically, P4 colocalized with the ER, disrupted ER homeostasis, and triggered ER stress through the upregulation of proteins associated with the unfolded protein response, thus provoking abundant cytoplasmic vacuoles through the dilation of ER and resultant tumor paraptosis, a non-apoptotic mode of cell death. Overall, this study lays the groundwork for the precise design and synthesis of supramolecular bioactive agents derived from methylated β-cyclodextrin by precisely modulating their chemical structures.</div></div><div><h3>Statement of significance</h3><div>Cyclodextrin-based supramolecular bioactive nanoagents could be employed for tumor management. However, there are challenges in developing β-cyclodextrin-derived bioactive nanoagents and tuning their structure-activity relationship to enhance their antitumor effects. Herein, we synthesized several bioactive nanoagents utilizing HPMA and PMCD by meticulously modulating their dendronized structures. It was revealed that P4, which was featured with the highest proportion of PMCD on its side chains, could distinctly interact with the ER. This enhanced interaction disrupted ER homeostasis, resulting in pronounced ER stress and paraptosis in tumor cells. Additionally, P4 exhibited efficient tumor retention and effective antitumor activity <em>in vivo</em>. This study demonstrated that biological function of β-cyclodextrin-derived bioactive nanoagents could be enhanced through optimization of the PMCD proportion on their side chains.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 436-450"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400988","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":"Erratic calcareous deposits: Biotic formation insights and biomineralising bacterial strain isolation","authors":"Beatrice Farda,&nbsp;Amedeo Mignini,&nbsp;Rihab Djebaili,&nbsp;Paola Cacchio,&nbsp;Maddalena Del Gallo,&nbsp;Marika Pellegrini","doi":"10.1016/j.actbio.2025.02.032","DOIUrl":"10.1016/j.actbio.2025.02.032","url":null,"abstract":"<div><div>The present study investigated the contribution of microbial communities in producing \"living stones\" and the suitability of these clasts as sources of microorganisms with biomineralisation abilities. The calcareous samples were analysed for their microbial community (16S rRNA gene metabarcoding and culturable approach) and <em>in vitro</em> regeneration tests. Scanning electron microscopy and Energy Dispersive Spectroscopy (SEM-EDX) were applied to investigate microbial aggregation structures and footprints in natural and <em>in vitro</em> samples. The metabarcoding unveiled amplicon sequence variants (ASVs) assigned to lineages with biomineralisation abilities (<em>e.</em>g<em>.</em>, Proteobacteria and Actinobacteriota). The culturable approach resulted in nineteen calcifying isolates with diverse morphological, metabolic, and mineral precipitation properties. Based on mineralising properties, <em>Stenotrophomonas maltophilia, Lysinbacillus fusiformis</em>, and <em>Microbacterium ginsengiterrae</em> were identified at the molecular level. <em>In vitro</em> regeneration tests and SEM-EDX analyses confirmed the active role of the endogenous microorganisms in forming these “living stones”. These findings allow us to hypothesise an essential role of microbial precipitation in forming these “living stones”, previously described as of abiotic origin. The current study findings provide a solid scientific foundation for future investigations. The obtained bacterial isolates and their potential applications in bioremediation, construction, and cultural heritage restoration demonstrate the direct applicability of our study in sectors involving biomaterials application.</div></div><div><h3>Statement of significance</h3><div>We studied some \"living stones\" that can be found worldwide and whose origin is still not completely understood. Geologists have not yet fully explained the origin of these inorganic structures that grow in size over time. The results obtained from our microbiological investigations allowed us to discover that microorganisms play a crucial role in forming these masses. In the investigations of the structures and microbial communities within the stones, we identified specific bacteria that actively contribute to forming minerals and isolated bacteria that can form biominerals. These findings deepen our understanding of natural processes involved in the formation of these structures and show their potential for several applications (<em>e.</em>g<em>.</em>, building materials or cultural heritage preservation).</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 256-265"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426832","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}