Acta Biomaterialia最新文献

{"title":"Flexible beam-based microelectrode arrays integrated with oriented nanofiber scaffolds for electrophysiological monitoring of cardiac tissue","authors":"Wangzihan Zhang ,&nbsp;Mingcheng Xue ,&nbsp;Hang Jin ,&nbsp;Jianhui Yang ,&nbsp;Huiquan Wu ,&nbsp;Bin Qiu ,&nbsp;Yuqing Jiang ,&nbsp;Feng Xu ,&nbsp;Bin Lin ,&nbsp;Weiwei Kong ,&nbsp;Jianzheng Cen ,&nbsp;Songyue Chen ,&nbsp;Daoheng Sun","doi":"10.1016/j.actbio.2025.06.005","DOIUrl":"10.1016/j.actbio.2025.06.005","url":null,"abstract":"<div><div><em>In vitro</em> culture and electrophysiological monitoring of engineered cardiac tissue (ECT) are crucial for the screening and evaluation of cardiotoxic drugs. Microelectrode arrays (MEAs) offer significant advantages in non-invasive, high-throughput detection. However, existing MEAs face challenges in replicating the natural growth environment of cardiomyocytes, which hinders the morphology and functional maturation of cells. In this study, a flexible beam-based microelectrode array (BMEA) integrated with nanofiber scaffolds is presented for the culturing of well-aligned cardiac tissue and the monitoring of electrophysiological signals. Oriented nanofibers are suspended on flexible polydimethylsiloxane beams to create a 3D culture environment for tissue. The BMEA exhibits low impedance (22 ± 7 kΩ@1 kHz for electrode width of 100 μm), stable electrochemical performance, and good biocompatibility. Through a 10-day continuous culture and drug stimulation of human induced pluripotent stem cell-derived cardiomyocytes, the device demonstrates the ability to capture the electrophysiological signals dynamically while promoting the structural and functional maturation of cardiomyocytes, which show better cell orientation, larger cell size, and faster conduction velocity (∼ 21 cm/s). Further drug tests validate the effectiveness of this device. The BMEA provides a perspective tool for screening and evaluation of drug cardiotoxicity to cardiac tissues.</div></div><div><h3>Statement of significance</h3><div>The mechanical mismatch between traditional rigid MEAs and flexible biological tissues has been partially addressed by the development of flexible MEAs based on polymer or hydrogel substrates. However, these 2D adherent culture methods still face several limitations, including lack of biomimetic ECM microstructure, insufficient intercellular interactions, and directional access to nutrients, thereby posing challenges to the growth of cardiac tissue and the maturation of its electrophysiological functions. Herein, a flexible PDMS beam-based microelectrode array (BMEA) integrated with oriented nanofiber scaffolds is proposed for in-situ electrophysiological monitoring of aligned cardiac tissue in a suspended and biomimetic 3D culture environment. The BMEA provides a promising tool for screening and evaluation of drug cardiotoxicity to cardiac tissues.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 309-319"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251268","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":"Engineering of bioprosthetic heart valves with synergistic zwitterionic surface modification and zirconium cross-linking for improved biocompatibility and durability","authors":"Kaijun Li ,&nbsp;Qinsheng Hu ,&nbsp;Ling Wang ,&nbsp;Chengcheng Wu ,&nbsp;Li Yang ,&nbsp;Gongyan Liu ,&nbsp;Yunbing Wang","doi":"10.1016/j.actbio.2025.06.010","DOIUrl":"10.1016/j.actbio.2025.06.010","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Bioprosthetic heart valves (BHVs) are frequently utilized in surgeries for heart valve replacement to address valvular heart disease (VHD). Despite their widespread use, BHVs still face challenges in clinical applications, such as thrombosis, calcification, immune responses, poor re-endothelialization, infection, component degradation, and mechanical failure, which are largely due to the heterogeneous cross-linking effects. To address these issues, we propose a synergistic engineering strategy based on sequential zwitterionic surface modification and zirconium cross-linking to improve the biocompatibility and durability of BHVs. After surface modification via ring-opening reactions of zwitterionic epoxy copolymers (PGSB) on collagen fibers of decellularized porcine pericardium (D-PP), the zwitterionic PGSB significantly promoted the uniform transfer of zirconium ions (Zr&lt;sup&gt;4+&lt;/sup&gt;) and further coordinated with Zr&lt;sup&gt;4+&lt;/sup&gt; to achieve homogeneous cross-linking between collagen fibers. Compared to conventional glutaraldehyde (GA)-cross-linked PP, PGSB/Zr-PP showed enhanced anti-thrombotic performance, attenuated immune rejection, accelerated endothelialization, and over 95 % reduction in calcification after 90 days of subcutaneous implantation, collectively indicating improved biocompatibility. Furthermore, this homogeneously cross-linked PGSB/Zr-PP exhibited undetectable component degradation and simultaneous improvements in both strength and toughness, all of which are essential for improving the durability of BHVs. Intriguingly, the zwitterionic sulfobetaine groups could be converted into bactericidal quaternary ammonium groups upon coordination with Zr&lt;sup&gt;4+&lt;/sup&gt;, resulting in strong antibacterial and anti-biofilm activities beneficial for preventing life-threatening prosthetic valve endocarditis. More importantly, PGSB/Zr-PP met the ISO 5840–3 standards required for BHV applications in terms of hydrodynamic performance and 200-million-cycle durability. These results demonstrate that PGSB/Zr-PP would be a promising alternative to GA-cross-linked BHVs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;Mainstream glutaraldehyde-cross-linked BHV face persistent clinical challenges, including thrombosis, calcification, immune response, poor re-endothelialization, infection, component degradation, and mechanical failure. Although various non-glutaraldehyde cross-linkers have been investigated, few strategies effectively address these challenges due to the heterogeneous nature of cross-linking. Herein, we present a synergistic engineering strategy based on sequential zwitterionic surface modification and zirconium cross-linking. This strategy produces homogeneously cross-linked BHVs with comprehensive improvements in anti-thrombogenicity, immune compatibility, endothelialization, resistance to calcification and infection, enzymatic stability, and mechanical strength. Notably, the aortic BHV fabricated via this method met the IS","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 266-282"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259537","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":"Gradients in lacunar morphology and cartilage mineralization reflect the mechanical function of the mouse femoral head epiphysis","authors":"Tengteng Tang ,&nbsp;Jingxiao Zhong ,&nbsp;Jingrui Hu ,&nbsp;Victoria Schemenz ,&nbsp;Anton Davydok ,&nbsp;Roland Brunner ,&nbsp;Jun Zhou ,&nbsp;Wolfgang Wagermaier ,&nbsp;Andrew A. Pitsillides ,&nbsp;William J. Landis ,&nbsp;Peter Fratzl ,&nbsp;Junning Chen","doi":"10.1016/j.actbio.2025.06.002","DOIUrl":"10.1016/j.actbio.2025.06.002","url":null,"abstract":"<div><div>Mouse femurs are widely used to study bone development and disorders. The mammalian femoral head epiphysis, located between articular cartilage and a growth plate, critically maintains joint integrity during weight-bearing and supports femoral growth. Murine femoral head epiphyses are unusual in having no secondary ossification center (SOC). In this regard, a key question arises: How is the extracellular matrix (ECM) of the mouse femoral head epiphysis structured to balance the competing demands of mechanical stability and nutrient transport in the absence of a SOC? This study investigates the microstructure and ECM organization of normal young mouse femoral head epiphyses across multiple length scales and identifies distinct gradients in lacunar size, shape, mineral content, and collagen and mineral organization. Chondrocyte lacunae in deep epiphyseal zones are significantly larger, more spherical and interconnected, compared to the lacunae near the tidemark and growth plate. Enlarged lacunae and increased tissue porosity in the deep zones are associated with higher ECM mineralization, compensating for reduced stiffness from the porosity while maintaining compliance that may facilitate fluid flow and nutrient diffusion to enlarged cells. This study highlights an optimization strategy of murine proximal femoral epiphyses driven by mechanical and biological demands and it offers insights for designing engineered constructs.</div></div><div><h3>Statement of Significance</h3><div>The mouse femoral head epiphysis lacks a secondary ossification center (SOC) and is instead entirely comprised of calcified cartilage at a young age. Given that the SOC is thought to be essential for joint function in mammals, a key question arises: How does the young mouse femoral head epiphysis sustain chondrocyte viability while supporting mechanical function? Using multiscale 3D structural characterization, we identify unique gradients in chondrocyte lacunar morphology and extracellular matrix (ECM) organization. Our findings reveal a finely tuned balance between porosity-driven nutrient transport and mineralization-enhanced mechanical stability, offering novel insights into cartilage biology and functionality. These structural principles provide a foundation for biomimetic scaffold design in regenerative medicine, making this work highly relevant to the field of biomaterials and orthopedic tissue engineering.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 385-399"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236207","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 nanoplatform mediates hypoxia-adenosine axis disruption and PD-L1 knockout for enhanced MRI-guided chemodynamic-immunotherapy","authors":"Mengyu Sun ,&nbsp;Cheng Ni ,&nbsp;Aiyu Li ,&nbsp;Junjie Liu ,&nbsp;Honghua Guo ,&nbsp;Fanyong Xu ,&nbsp;Kangan Li ,&nbsp;Xueyan Cao ,&nbsp;Xiangyang Shi ,&nbsp;Rui Guo","doi":"10.1016/j.actbio.2025.06.021","DOIUrl":"10.1016/j.actbio.2025.06.021","url":null,"abstract":"<div><div>Malignant melanoma is an extremely aggressive and fatal form of skin cancer due to the limited efficacy of conventional therapies. While immune checkpoint blockade therapy and chemodynamic therapy (CDT) have emerged as promising strategies for melanoma treatment, their effectiveness is compromised by the immunosuppressive and complex tumor microenvironment (TME). Here, cancer cell membrane-camouflaged nanoplatforms (PPMC@CM) were developed to co-deliver the CRISPR/Cas9-PD-L1 system and manganese dioxide nanoparticles (MnO₂ NPs) for magnetic resonance imaging (MRI)-guided CDT and enhanced immunotherapy. The formed PPMC@CM could efficiently accumulate at tumor sites by homologous targeting, generate O₂ to relieve hypoxia, and deplete glutathione (GSH) to enhance Mn²⁺-mediated Fenton-like reactions for enhanced CDT. Meanwhile, CRISPR/Cas9-mediated PD-L1 knockout effectively suppressed the PD-L1 expression, while hypoxia relief attenuated the immunosuppressive hypoxia-CD39/CD73-adenosine (ADO) pathway, thereby boosting the PD-L1-mediated immunotherapy. <em>In vivo</em> experimental results demonstrated that PPMC@CM nanoplatform could efficiently inhibit the growth and metastasis of melanoma by enhanced CDT and amplified immunotherapy, and provide targeted MRI of tumors. This work presents a novelty strategy to design biomimetic theranostic nanoplatform for melanoma by the combination of CDT and improved immunotherapy with CRISPR/Cas9-PD-L1 system and hypoxia-ADO axis inhibition.</div></div><div><h3>Statement of significance</h3><div>Malignant melanoma is a highly aggressive and treatment-refractory skin cancer, where conventional therapies exhibit limited efficacy and immune checkpoint blockade (ICB) is often compromised by the immunosuppressive tumor microenvironment (TME). To address these challenges, we developed a biomimetic nanoplatform (PPMC@CM) to codeliver MnO₂ nanoparticles and the CRISPR/Cas9-PD-L1 gene-editing system for MRI-guided chemodynamic therapy and enhanced immunotherapy. The PPMC@CM nanoplatform could efficiently accumulate at tumor sites by homologous targeting and relieve hypoxia to suppress the hypoxia-CD39/CD73-adenosine immunosuppressive axis. Additionally, the CRISPR/Cas9-mediated PD-L1 knockout significantly suppresses PD-L1 expression, thereby boosting ICB efficacy. Moreover, PPMC@CM could deplete glutathione in the TME to amplify Mn²⁺-mediated Fenton-like reactions for enhanced chemodynamic therapy. This research represents a promising theranostic nanoplatform for melanoma by combining chemodynamic therapy and immunotherapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 618-632"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295475","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":"Clickable PEG-norbornene microgels support suspension bioprinting and microvascular assembly","authors":"Irene W. Zhang ,&nbsp;Lucia S. Choi ,&nbsp;Nicole E. Friend ,&nbsp;Atticus J. McCoy ,&nbsp;Firaol S. Midekssa ,&nbsp;Michael M. Hu ,&nbsp;Eben Alsberg ,&nbsp;Sasha Cai Lesher-Pérez ,&nbsp;Jan P. Stegemann ,&nbsp;Brendon M. Baker ,&nbsp;Andrew J. Putnam","doi":"10.1016/j.actbio.2025.06.006","DOIUrl":"10.1016/j.actbio.2025.06.006","url":null,"abstract":"<div><div>The development of perfusable and multiscale vascular networks remains one of the largest challenges in tissue engineering. As such, there is a need for the creation of customizable and facile methods to produce robustly vascularized constructs. In this study, secondarily crosslinkable (clickable) poly(ethylene glycol)-norbornene (PEGNB) microbeads were produced and evaluated for their ability to sequentially support suspension bioprinting and microvascular self-assembly towards the aim of engineering hierarchical vasculature. The clickable PEGNB microbead slurry exhibited mechanical behavior suitable for suspension bioprinting of sacrificial bioinks, could be UV crosslinked into a granular construct post-print, and withstood evacuation of the bioink and subsequent perfusion of the patterned void space. Endothelial and stromal cells co-embedded within jammed RGD-modified PEGNB microbead slurries assembled into capillary-scale vasculature after secondary crosslinking of the beads into granular constructs, with endothelial tubules forming within the interstitial space between microbeads and supported by the perivascular association of the stromal cells. Microvascular self-assembly was not impacted by printing sacrificial bioinks into the cell-laden microbead support bath before UV crosslinking. Collectively, these results demonstrate that clickable PEGNB microbeads are a versatile substrate for both suspension printing and microvascular culture and may be the foundation for a promising methodology to engineer hierarchical vasculature.</div></div><div><h3>Statement of significance</h3><div>In this study, we leveraged and combined advances in microgel biomaterials, granular hydrogels, suspension bioprinting, and vascular biology to create relatively large volume (&gt;500 mm³) vascularized constructs. We fabricated secondarily crosslinkable (clickable) poly(ethylene glycol)-norbornene (PEGNB) microbeads and demonstrated their ability to sequentially support suspension bioprinting and microvascular self-assembly towards the aim of engineering hierarchical vasculature. To the best of our knowledge, this is the first study that uses PEG microgels as supportive materials for bioprinting, and one of the first papers to document microvascular self-assembly within granular constructs. The combination of top-down and bottom-up approaches <em>within a single construct</em> represents a significant and innovative contribution that we believe will be of broad interest to the biomaterials and regenerative medicine communities.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 283-296"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295477","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":"Degeneration mechanisms and advancements in optimization for preparation and crosslinking strategy of pericardium-based bioprosthetic heart valves","authors":"Xueyu Huang ,&nbsp;Bangquan Wei ,&nbsp;Lepeng Chen ,&nbsp;Li Yang ,&nbsp;Cheng Zheng ,&nbsp;Yunbing Wang","doi":"10.1016/j.actbio.2025.05.062","DOIUrl":"10.1016/j.actbio.2025.05.062","url":null,"abstract":"<div><div>Valvular heart disease (VHD), clinically manifested as the malfunction of heart valves, greatly threatens public health worldwide. The morbidity and mortality of VHD increase significantly with age, and the high prevalence of VHD in aging society has prompted the urgency for effective treatment. Prosthetic heart valve replacement is currently recognized as the gold standard for VHD treatment. Bioprosthetic heart valves (BHVs), generally manufactured from glutaraldehyde crosslinked xenogeneic tissue, exhibited better hemodynamics and lower thrombogenicity than mechanical heart valves (MHVs) and could be implanted by transcatheter valve replacement systems, which markedly improved the efficiency of VHD therapy, especially for the elderly patients. However, BHVs degenerate within 10–15 years after implantation, which is greatly associated with their defects including cytotoxicity, calcification, immune response, matrix degradation, mechanical damage, and thrombosis. To prolong the service life of BHVs, recent studies have developed a series of innovative modification strategies to improve the biocompatibility, mechanical performance, matrix components stability, anticalcification, and antithrombotic properties of conventional glutaraldehyde crosslinked BHVs. Moreover, a series of new crosslinking and modification strategies have been proposed and developed to fabricate non-glutaraldehyde crosslinked BHVs with good stability, biocompatibility, hemocompatibility, anticalcification property, durability, and hydrodynamics. In this review, we first summarized the defects of BHVs and the related reasons from the perspective of biomaterials, and then comprehensively detailed the functional modification strategies for BHVs based on glutaraldehyde crosslinking. We provided detailed insights into novel non-glutaraldehyde crosslinking and modification strategies for BHVs. Finally, the current challenges and prospects of BHVs were also discussed.</div></div><div><h3>Statement of significance</h3><div>Bioprosthetic heart valves (BHVs) currently face challenges such as cytotoxicity, thrombosis, calcification, and immunoinflammatory responses, which contribute to structural valve degeneration and reduce the longevity of BHVs. This review provides a comprehensive introduction to the detailed defects associated with glutaraldehyde crosslinked BHVs from the perspective of biomaterials. It then thoroughly elaborates on the modification strategies based on glutaraldehyde crosslinking, as well as detailed insights into novel non-glutaraldehyde crosslinking strategies for BHVs. Finally, the challenges and prospects facing BHVs are discussed.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 51-74"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153002","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":"Bovine amniotic membrane with antioxidant and anti-inflammatory properties for the repair of alkali-burned corneas","authors":"Mengna Guo ,&nbsp;Kai Wu ,&nbsp;Mei Yang ,&nbsp;Yue Yin ,&nbsp;Zhe Li ,&nbsp;Guoqing Wang ,&nbsp;Jing Sun ,&nbsp;Hongsong Fan","doi":"10.1016/j.actbio.2025.05.054","DOIUrl":"10.1016/j.actbio.2025.05.054","url":null,"abstract":"<div><div>Corneal alkali burns are a common ocular emergency that can lead to blindness, marked by inflammation and delayed epithelial healing due to elevated oxidative stress in the intraocular environment. Mitigating the levels of reactive oxygen species (ROS) and the inflammatory response is essential for developing corneal repair materials. Amniotic membrane (AM) is frequently employed for ocular surface repair but faces limitations such as limited availability and rapid degradation. This study developed a crosslinked decellularized bovine amniotic membrane (CAM) with high transparency, enhanced mechanical strength, and enzyme resistance. By introducing Manganese-based carbon dots (Mn CDs), the composite (CDs@CAM) retained the physical properties of CAM meanwhile brought in the multi-enzyme activities of Mn CDs. Extensive characterizations demonstrated CDs@CAM high CAT-like activity, SOD-like activity and scavenging ability of hydroxyl radical and nitrogen radical. Furthermore, cellular and animal experiments demonstrated that the CDs@CAM possessed good biocompatibility, strong antioxidant capabilities, and anti-inflammatory effects, and thus significantly promoted corneal epithelial regeneration, inhibited neovascularization, and prevented scarring in alkali burn repair. This study offers a feasible strategy for artificial corneas and corneal disease treatment.</div></div><div><h3>Statement of Significance</h3><div>In this study, we developed a crosslinked decellularized bovine amniotic membrane (CAM) integrated with manganese-based carbon dots (Mn CDs), creating a composite material (CDs@CAM) that addressed the issue of high oxidative stress and severe inflammation in the eye caused by corneal alkali burns. Different from the conventional amniotic membrane products, CDs@CAM retains advantageous physical properties and biocompatibility of CAM while offering potent antioxidant and anti-inflammatory capabilities. We confirmed its good biocompatibility, as well as reductions in intracellular ROS levels and inflammatory responses. Importantly, in an alkali-burned cornea model, we revealed its outstanding performance in promoting corneal epithelial repair, inhibiting neovascularization, and thus preventing scarring, restoring corneal thickness and clarity to normal levels.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 198-211"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144850","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":"Apolipoprotein E as a potential regulator of osteoclast-osteoblast coupling in material-induced bone formation","authors":"Yue Wang ,&nbsp;Zhangling Nie ,&nbsp;Huaze Liu ,&nbsp;Joost D. de Bruijn ,&nbsp;Huipin Yuan ,&nbsp;Chongyun Bao","doi":"10.1016/j.actbio.2025.05.070","DOIUrl":"10.1016/j.actbio.2025.05.070","url":null,"abstract":"<div><div>Osteoinductive materials which induce bone formation in non-osseous sites are promising bone substitutes to repair critical-sized bone defects. It appears that innate immune response (esp. osteoclastogenesis) to materials plays an important role in material-induced bone formation. In this study, the coupling between osteoclastogenesis and subsequent osteogenesis in material-induced bone formation was investigated. Osteoclastogenesis of mouse bone marrow-derived monocytes (BMMs) on osteoinductive tricalcium phosphate (TCPs) and non-osteoinductive tricalcium phosphate (TCPb) ceramics were evaluated with high-throughput RNA sequencing (RNA-seq) and RT-qPCR regarding secretory proteins. It turned out that osteoinductive TCPs supported osteoclastogenesis and enhanced Apolipoprotein E (ApoE) production. Meanwhile, ApoE enhanced osteogenic gene expression (<em>Alp, Runx2, Col1a1, Osterix</em>) and ALP staining and activity of CRL-12424 cells <em>in vitro</em>. Additionally, western blot assay revealed that ApoE played its role in osteogenesis of CRL-12424 by activating JAK-STAT pathway instead of PI3K-AKT pathway. The overall data indicated that ApoE was a potential coupling factor between osteoclastogenesis and osteogenesis in material-induced bone formation. By secreting ApoE, osteoclasts formed on osteoinductive materials stimulated osteogenic differentiation of osteo-progenitors via JAK-STAT pathway.</div></div><div><h3>Statement of significance</h3><div>Osteoinductive materials can repair critical-sized bone defects, while the precise mechanism osteoinductive materials driving bone formation remains unclear. Recent research has highlighted the role of osteoclastogenesis in material-induced bone formation, how osteoclastogenesis playing its role in osteogenesis was subjected to investigation in the current study. Robust ApoE gene expression shown in osteoclastogenesis with the osteoinductive material and ApoE enhancing osteogenesis of mesenchymal stromal cells (CRL-12424) indicated ApoE as a potential regulator of osteoclast-osteoblast coupling, providing thus novel insights into the complex interplay of cellular responses and contributing to the development of more effective bone substitute materials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 633-647"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192588","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":"Reciprocal folding dynamics in cellular networks at the stroma-basement membrane interface","authors":"Youngmin Jo ,&nbsp;Donghyun Yim ,&nbsp;Chan E Park ,&nbsp;Insung Yong ,&nbsp;Jongbeom Lee ,&nbsp;Kwang Ho Ahn ,&nbsp;Chanhee Yang ,&nbsp;Jae-Byum Chang ,&nbsp;Taek-Soo Kim ,&nbsp;Jennifer Hyunjong Shin ,&nbsp;Taeyoon Kim ,&nbsp;Pilnam Kim","doi":"10.1016/j.actbio.2025.05.069","DOIUrl":"10.1016/j.actbio.2025.05.069","url":null,"abstract":"<div><div>Epithelium layer stands on a membrane, called basement membrane (BM) which serves as a boundary with the underlying stroma. While most studies on morphogenesis have focused on the epithelium-BM complex, the role of the BM-stroma interface remains poorly understood. In this study, we demonstrate how forces originating from the stromal layer contribute to tissue morphogenesis. Folds focalization at the BM-stroma interface is driven by mechanical instability, which arises from the fluidity of the stroma and the polarized tractional forces acting on the rigid membrane of stromal cell condensates. Stromal cells move towards the folded region by topographic guidance, while the concentration of forces intensifies. Through this process, stromal cells and folds engage in recursive interactions, resulting in the formation of a cellular network. Our observation provides a rational mechanism for pattern formation in a multi-layered living tissue.</div></div><div><h3>Statement of significance</h3><div>This study addresses a crucial gap in understanding how stromal cells interact with the basement membrane to lead tissue surface morphogenesis. By developing a collagen-based, nanometer-thick engineered basement membrane, we demonstrate that the stromal cells exert traction forces on the basement membrane to fold. The folding process guides stromal cell migration, which in turn induces further folding in a recursive manner. The direction of folding, invagination or evagination, is determined by the stiffness difference between the stroma and the basement membrane. This model offers better understanding about how the basement membrane interacts with stromal cells to make evaginated network structures on tissue surface.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 360-371"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192590","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":"Mucoadhesive micellar eyedrops for the treatment of ocular inflammation","authors":"Yuting Zheng ,&nbsp;Yimin Gu ,&nbsp;Yavuz Oz ,&nbsp;Liangju Kuang ,&nbsp;Ann Yung ,&nbsp;Seokjoo Lee ,&nbsp;Reza Dana ,&nbsp;Nasim Annabi","doi":"10.1016/j.actbio.2025.05.065","DOIUrl":"10.1016/j.actbio.2025.05.065","url":null,"abstract":"<div><div>Efficient ocular drug delivery remains a significant challenge in treating eye inflammation due to physiological barriers such as the tear film and frequent blinking, which lead to rapid drug clearance. Commercial eyedrops, like Oceanside<em>®</em> (0.5 % loteprednol etabonate (LE) ophthalmic suspension), suffer from low ocular bioavailability and require frequent dosing to maintain therapeutic levels. To address these limitations, we developed a mucoadhesive micellar drug delivery system to enhance the bioavailability and retention of LE on the cornea. Our system employed polymeric micelles (MCs) functionalized with phenylboronic acid (PBA), which exhibited high conjugation efficiency to enable strong binding to the mucin-rich corneal layer. These MCs were synthesized using PBA-functionalized poly (ethylene glycol)-<em>b</em>-poly (<em>N</em>-(2-hydroxypropyl) methacrylamide-oligolactate) (PBA-PEG-<em>b</em>-p(HPMA-Lac_m)) and subsequently dispersed into a shear-thinning matrix solution to form a micellar eyedrop formulation. The resulting eyedrop demonstrated a sustained LE release over 12 days, enabling prolonged therapeutic exposure. <em>In vitro, ex vivo,</em> and <em>in vivo</em> studies confirmed enhanced mucoadhesion and extended corneal retention. The formulation was biocompatible with human corneal epithelial cells and demonstrated ocular safety in mice. In a murine model of electrocautery-induced corneal inflammation, a once-daily administration of LE-loaded PBA-MC eyedrops significantly reduced corneal opacity, preserved corneal structure, and lowered immune cell infiltration and cytokine levels. Notably, the therapeutic efficacy of the LE-loaded PBA-MC eyedrops matched that of commercial Oceanside<em>®</em>, which required four daily doses. These findings suggest that the engineered PBA-MC eyedrops could serve as a promising platform for ocular drug delivery, addressing the challenges associated with treating eye inflammation effectively.</div></div><div><h3>Statement of significance</h3><div>Mucoadhesive nanoparticles used for ocular drug delivery often suffer from low attachment efficiency, limiting their effectiveness. Additionally, the lack of <em>in vivo</em> comparisons with commercial eye drops hinders evaluating their clinical benefits.</div><div>To address these issues, we developed PBA-functionalized polymeric MCs to enhance the bioavailability of LE by increasing its retention on the corneal mucin layer. These MCs showed high PBA conjugation efficiency, a 12-day sustained release of LE, strong mucin adhesion, <em>in vitro</em> and <em>in vivo</em> biocompatibility. In a mouse model of corneal inflammation, a once-daily LE-loaded micellar eyedrop matched the efficacy of the commercial LE eyedrop (Oceanside®, 0.5 %), which was dosed four times daily, reducing corneal opacity, preserving corneal structure, and decreasing inflammation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 517-533"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188614","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}