Acta Biomaterialia最新文献_第2页

Rapid biofilm disruption by ionic buffers enables calcium phosphate cement functionalization 离子缓冲液快速破坏生物膜使磷酸钙水泥功能化。

IF 10.4 1区医学 Q1 ENGINEERING, BIOMEDICAL

Acta Biomaterialia

Pub Date : 2026-10-01 Epub Date: 2026-08-19 DOI: 10.1016/j.actbio.2026.08.034

Ayden Watt, Nitin chandra teja Dadi, Sze Wai Lau, Joshua Vorstenbosch, Geraldine Merle, Adam Hart, Michael Tanzer, Jake Barralet

Antimicrobial resistance and biofilm-associated infections continue to undermine standard antibiotic therapies, prompting the need for physicochemical adjuvant strategies. In this study, we evaluated the antibiofilm and antimicrobial activity of 7 biological buffer systems including citrate, acetate, sodium phosphate, potassium phosphate, borate, carbonate, and Tris-buffered saline against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA). Using a range of biofilm, metabolic, and cytotoxicity assays coupled with bioluminescence imaging, we demonstrate that low-concentration (20 mM) buffers significantly disrupted metabolic activity and biofilm structure within minutes of exposure as indicated by rapid functional perturbations observed via bioluminescence and without cytotoxicity in human dermal fibroblasts. Among the tested solutions, citrate emerged as the most potent antibiofilm agent (>50% reduction), while acetate, borate, and phosphate systems also demonstrated significant antibiofilm activity (25–50% reduction). MRSA exhibited reduced sensitivity to buffer treatment, consistent with known stress-response adaptations. Biofilm reduction >50% was recapitulated in three functionalized brushite cement formulations prepared with selected buffer systems, supporting the feasibility of incorporating chemically active ionic additives into calcium phosphate biomaterials. These findings highlight the potential of ionic systems as non-antibiotic antimicrobial agents and therapeutic adjuvants. Strategic integration into biomaterial design or wound irrigation strategies carries significant promise as a non-antibiotic strategy to combat infection.

Statement of significance

Biofilm-associated infections remain difficult to treat because bacteria in biofilms are far less responsive to antibiotics. This study shows that several simple biological buffer systems, especially citrate, can rapidly disrupt Staphylococcus aureus biofilms at low concentrations without harming human dermal fibroblasts. Beyond identifying these ionic solutions as non-antibiotic antibiofilm agents, the work also shows that their activity can be translated to calcium phosphate cements, creating biomaterials with infection-modulating properties. This is significant because it introduces a simple and scalable strategy to design antimicrobial biomaterials without relying on conventional antibiotics, metallic agents, or toxic additives, which is of broad interest to researchers developing safer materials for infection control and regenerative medicine.

抗菌素耐药性和生物膜相关感染继续破坏标准抗生素治疗，促使需要物理化学辅助策略。在这项研究中，我们评估了7种生物缓冲体系（包括柠檬酸盐、醋酸盐、磷酸钠、磷酸钾、硼酸盐、碳酸盐和tris缓冲盐水）对甲氧西林敏感和耐甲氧西林金黄色葡萄球菌（MSSA和MRSA）的抗菌膜和抗菌活性。利用一系列生物膜、代谢和细胞毒性实验，结合生物发光成像，我们证明了低浓度（20 mM）缓冲液在暴露几分钟内显著破坏了代谢活性和生物膜结构，这是通过生物发光观察到的快速功能扰动所表明的，并且在人类真皮成纤维细胞中没有细胞毒性。在测试的溶液中，柠檬酸盐是最有效的抗生物膜剂（减少50%），而醋酸盐、硼酸盐和磷酸盐系统也表现出显著的抗生物膜活性（减少25-50%）。MRSA对缓冲处理的敏感性降低，与已知的应激反应适应一致。生物膜还原bbb50 %在三种功能化刷石水泥配方中重现，这些配方由选定的缓冲系统制备，支持将化学活性离子添加剂加入磷酸钙生物材料的可行性。这些发现突出了离子系统作为非抗生素抗菌剂和治疗佐剂的潜力。与生物材料设计或伤口冲洗策略的战略整合作为对抗感染的非抗生素策略具有重要的前景。意义声明：生物膜相关感染仍然难以治疗，因为生物膜中的细菌对抗生素的反应要小得多。这项研究表明，几种简单的生物缓冲系统，特别是柠檬酸盐，可以在低浓度下快速破坏金黄色葡萄球菌生物膜，而不损害人皮肤成纤维细胞。除了将这些离子溶液确定为非抗生素的抗生物膜剂之外，该研究还表明，它们的活性可以转化为磷酸钙胶合剂，从而创造出具有感染调节特性的生物材料。这很重要，因为它引入了一种简单且可扩展的策略来设计抗菌生物材料，而不依赖于传统的抗生素、金属剂或有毒添加剂，这对开发用于感染控制和再生医学的更安全材料的研究人员具有广泛的兴趣。

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引用次数: 0

From patterning precision to biological performance: Oxide layer kinetics in gallium-based liquid metals 从图案精度到生物性能：镓基液态金属的氧化层动力学。

IF 10.4 1区医学 Q1 ENGINEERING, BIOMEDICAL

Acta Biomaterialia

Pub Date : 2026-10-01 Epub Date: 2026-08-13 DOI: 10.1016/j.actbio.2026.08.021

Suqin Han, Yurong Guo, Lan Bao, Yingying Jing, Yen Leng Pak, Xing Gao, Liwei Chen, Duo Liu, Jibin Song

Gallium-based liquid metals (GaLMs) have emerged as transformative materials for biomedical devices, flexible electronics, and soft robotics, owing to their room-temperature fluidity, high electrical conductivity, and favorable biocompatibility. However, achieving high-resolution patterning and predictable biological performance remains challenging due to the dynamic native Ga₂O₃ oxide layer, whose formation, rupture, passivation, and reformation govern interfacial wetting, charge transfer, and bio-interfacial interactions. This review critically examines how oxide layer kinetics provide a unifying framework linking patterning strategies to biological outcomes. We systematically evaluate four classes of patterning techniques, namely physical template, additive manufacturing, laser patterning, and selective wetting, based on their distinct oxide manipulation mechanisms, i.e., harnessed, transiently disrupted, permanently ablated, or locally eliminated. The resulting microstructural features, including oxide integrity, surface topography, and interface chemistry, dictate long‑term electrical stability, corrosion resistance, and tissue response. A three‑layer analytical framework is introduced to connect oxide properties to interfacial events and ultimately to biological outcomes. Evidence strength is graded to distinguish well‑established mechanisms from knowledge gaps, notably the lack of chronic in vivo data beyond six months and the unmonitored contact resistance drift under cyclic physiological loading. Finally, we identify future directions centered on oxide‑guided adaptive functionalities. This review provides a mechanistic foundation for rational design of GaLM‑based bioelectronics and highlights critical pathways toward clinical translation.

Statement of significance

• Establishes oxide layer kinetics (Ga₂O₃ formation and dissolution) as the unifying mechanism governing interfacial energy and patterning fidelity in gallium-based liquid metals. • Unifies state-of-the-art patterning strategies including injection, template printing, photolithography, direct writing, 3D printing, laser patterning, and selective wetting under a framework of interface engineering. • Demonstrates functional integration of patterned GaLMs into soft electrodes, electronic skins, implantable bioelectronics, and soft robotics with exceptional mechanical compliance and biocompatibility. • Outlines critical challenges such as contact resistance drift and proposes future directions including in situ oxide passivation, biodegradable composites, and stimuli-responsive architectures for clinical translation.

镓基液态金属（GaLMs）由于其室温流动性、高导电性和良好的生物相容性，已成为生物医学设备、柔性电子产品和软机器人的变革性材料。然而，由于动态的原生Ga2O3氧化层的形成、破裂、钝化和重组控制着界面润湿、电荷转移和生物界面相互作用，实现高分辨率的图案和可预测的生物性能仍然具有挑战性。这篇综述批判性地考察了氧化层动力学如何提供一个统一的框架，将模式策略与生物学结果联系起来。我们系统地评估了四类图像化技术，即物理模板、增材制造、激光图像化和选择性润湿，基于它们不同的氧化物操作机制，即利用、短暂破坏、永久消融或局部消除。由此产生的微观结构特征，包括氧化物完整性、表面形貌和界面化学，决定了长期的电稳定性、耐腐蚀性和组织响应。引入了一个三层分析框架，将氧化物性质与界面事件联系起来，并最终与生物结果联系起来。证据强度被分级，以区分已建立的机制与知识空白，特别是缺乏超过6个月的慢性体内数据和循环生理负荷下未监测的接触电阻漂移。最后，我们确定了以氧化物引导的自适应功能为中心的未来方向。这篇综述为合理设计基于GaLM的生物电子学提供了机制基础，并强调了临床转化的关键途径。•建立了氧化层动力学（Ga2O3的形成和溶解）作为控制界面能和基于镓的液态金属的图形保真度的统一机制。•在界面工程的框架下，统一了最先进的图案策略，包括注射、模板打印、光刻、直接书写、3D打印、激光图案和选择性润湿。•展示了图形化镓与软电极、电子皮肤、植入式生物电子学和软机器人的功能集成，具有卓越的机械顺应性和生物相容性。•概述了关键的挑战，如接触电阻漂移，并提出了未来的方向，包括原位氧化钝化，可生物降解的复合材料，以及临床翻译的刺激响应架构。

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引用次数: 0

An immune-activated co-culture model of patient-derived gastric cancer organoids and peripheral blood mononuclear cells for personalized chemotherapy screening 患者源性胃癌类器官和外周血单个核细胞的免疫激活共培养模型用于个性化化疗筛选。

IF 10.4 1区医学 Q1 ENGINEERING, BIOMEDICAL

Acta Biomaterialia

Pub Date : 2026-10-01 Epub Date: 2026-08-30 DOI: 10.1016/j.actbio.2026.08.053

Yefan Yu, Wei Chen, Ningfei Jia, Chen Wang, Juan Lan, Shuying Yan, Tiefeng Cao, Yan Huang, Rui L. Reis, Joaquim M. Oliveira, Leping Yan, Lin Xiao

<div><div>Selecting effective chemotherapy after immunotherapy remains a major clinical challenge in advanced gastric cancer because patient responses are highly heterogeneous. A major obstacle is the lack of personalized preclinical models that faithfully recapitulate the immune-activated tumor microenvironment (TME) following immunotherapy and enable evaluation of subsequent chemotherapy responses while preserving immune–tumor interactions. Here, we developed an immune-activated co-culture model comprising patient-derived gastric cancer organoids and autologous peripheral blood mononuclear cells (PBMCs). Immune activation was achieved using anti-PD-1-loaded gold nanocages (aPD-1@Au NCs), which integrate near-infrared-triggered photothermal tumor ablation with sustained anti-PD-1-mediated immune modulation. The resulting model recapitulates key features of the post-immunotherapy TME, including enhanced immune-cell infiltration, increased tumor-cell apoptosis, and CD8<sup>+</sup> T-cell activation. We then applied this model to evaluate five clinically relevant chemotherapeutic agents, including oxaliplatin, irinotecan, fluorouracil, doxorubicin, and docetaxel, for personalized chemotherapy screening after immunotherapy. Compared with monoculture organoids or non-activated co-cultures, the immune-activated model revealed drug-specific differences in tumor-killing efficacy, immune-mediated chemosensitization, and PBMC toxicity. Among the tested agents, oxaliplatin showed the strongest immune-mediated chemosensitization, whereas docetaxel achieved favorable tumor cell killing with relatively low immunotoxicity. These findings demonstrate that chemotherapy responses after immune activation are highly drug-specific, underscoring the importance of personalized chemotherapy selection following immunotherapy. As a proof-of-concept study, this work establishes an immune-activated patient-derived gastric cancer organoid–PBMC co-culture model that partially recapitulates the post-immunotherapy TME. This model provides a promising framework for developing personalized chemotherapy screening strategies after immunotherapy.</div></div><div><h3>Statement of significance</h3><div>Selecting effective chemotherapy after immunotherapy remains a major challenge in advanced gastric cancer because of substantial interpatient heterogeneity. Progress in personalized treatment is limited by the lack of preclinical models that faithfully recapitulate the post-immunotherapy tumor microenvironment (TME). Here, we developed an immune-activated co-culture model integrating patient-derived gastric cancer organoids with autologous peripheral blood mononuclear cells (PBMCs). Immune activation was achieved using anti-PD-1-loaded gold nanocages (aPD-1@Au NCs), which combine near-infrared-triggered photothermal tumor ablation with sustained aPD-1-mediated immune modulation. This platform preserves patient-specific tumor characteristics while capturing key immune–tumor interactions

在免疫治疗后选择有效的化疗仍然是晚期胃癌的主要临床挑战，因为患者的反应是高度异质性的。一个主要的障碍是缺乏个性化的临床前模型，这些模型忠实地概括了免疫治疗后的免疫激活肿瘤微环境（TME），并能够在保留免疫-肿瘤相互作用的同时评估随后的化疗反应。在这里，我们建立了一个免疫激活的共培养模型，包括患者来源的胃癌类器官和自体外周血单个核细胞（PBMCs）。免疫激活是使用抗pd -1负载的金纳米笼（aPD-1@Au NCs）实现的，它将近红外触发的光热肿瘤消融与持续的抗pd -1介导的免疫调节结合起来。由此产生的模型概括了免疫治疗后TME的关键特征，包括免疫细胞浸润增强、肿瘤细胞凋亡增加和CD8+ t细胞活化。然后，我们应用该模型评估了五种临床相关的化疗药物，包括奥沙利铂、伊立替康、氟尿嘧啶、阿霉素和多西紫杉醇，用于免疫治疗后的个性化化疗筛查。与单一培养的类器官或未激活的共培养相比，免疫激活模型在肿瘤杀伤效果、免疫介导的化学致敏和PBMC毒性方面显示出药物特异性差异。在测试的药物中，奥沙利铂表现出最强的免疫介导的化学致敏性，而多西紫杉醇以相对较低的免疫毒性获得了有利的肿瘤细胞杀伤。这些发现表明，免疫激活后的化疗反应具有高度的药物特异性，强调了免疫治疗后个性化化疗选择的重要性。作为一项概念验证研究，本研究建立了一个免疫激活的患者来源的胃癌类器官- pbmc共培养模型，该模型部分概括了免疫治疗后的TME。该模型为开发免疫治疗后的个性化化疗筛选策略提供了一个有希望的框架。意义声明：在免疫治疗后选择有效的化疗方案仍然是晚期胃癌患者面临的主要挑战，因为患者之间存在很大的异质性。个性化治疗的进展受到缺乏忠实地概括免疫治疗后肿瘤微环境（TME）的临床前模型的限制。在这里，我们建立了一种免疫激活的共培养模型，将患者来源的胃癌类器官与自体外周血单个核细胞（PBMCs）结合起来。免疫激活是使用抗pd -1负载的金纳米笼（aPD-1@Au NCs）实现的，它结合了近红外触发的光热肿瘤消融和持续的apd -1介导的免疫调节。该平台保留了患者特异性肿瘤特征，同时捕获了免疫治疗后关键的免疫肿瘤相互作用。使用该模型，我们评估了五种临床相关的化疗药物，并确定了肿瘤杀伤效果、免疫介导的化学致敏和免疫毒性方面的明显药物特异性差异。作为一项概念验证性研究，本工作为免疫治疗后的个性化化疗筛查建立了一个有希望的框架，并支持胃癌精确治疗策略的发展。

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引用次数: 0

A living therapeutic material to coordinate metabolic oxygenation and regenerative signaling in diabetic wounds 一种协调糖尿病伤口代谢氧合和再生信号的活性治疗材料。

IF 10.4 1区医学 Q1 ENGINEERING, BIOMEDICAL

Acta Biomaterialia

Pub Date : 2026-10-01 Epub Date: 2026-08-29 DOI: 10.1016/j.actbio.2026.08.052

Xi Zeng, Nana Gong, Guangyu Zhang, Yanhong Lu, Mingdong Cheng, Xiaohan Fan, Yujie Wang, Anwei Huang, Chi Hu, Jing Wang, Jing Zhang, Ming Zeng, Ziyi Yu

Diabetic chronic wounds remain difficult to treat because hypoxia and insufficient regenerative signaling persist. Although live biotherapeutics offer a promising route to local oxygenation therapy, current methods largely support a single microbial function rather than coordinate microbial oxygenation with regenerative cues. Here, we report a hydrogel living therapeutic material in which a crosslinked hyaluronic acid matrix coordinates a living metabolic module of Synechococcus elongatus with a regenerative module of platelet-rich plasma (PRP). The matrix enables injectability and rapid gelation while supporting microbial metabolic activity and modulating the local retention and release of PRP-derived growth factors. The resulting material sustains oxygen generation and preserves the viability of the living module. Particularly, it reduces intracellular ROS accumulation, promotes fibroblast migration, and enhances endothelial tube formation in vitro. In diabetic wounds, it accelerates wound closure and improves re-epithelialization, collagen remodeling, and angiogenesis. Transcriptomic analysis further reveals coordinated regulation of stimulus-response, immune-related, and cytokine- and chemokine-associated pathways. This work establishes a living therapeutic material framework for integrating microbial oxygenation with regenerative signaling for pathological wound microenvironment remodeling.

Statement of significance

Diabetic wounds are difficult to heal because damaged tissues often lack both oxygen and regenerative signals. Current living wound therapies mainly focus on microbial oxygen production, but they rarely coordinate oxygen supply with growth-factor-mediated tissue repair. This study develops an injectable living hydrogel that combines photosynthetic Synechococcus elongatus with platelet-rich plasma in a hyaluronic acid matrix. The material continuously generates oxygen, retains and releases regenerative factors, reduces oxidative stress, and promotes cell migration, angiogenesis, collagen remodeling, and wound closure. By integrating metabolic oxygenation with regenerative signaling, this work provides a strategy for remodeling pathological wound microenvironments and designing living therapeutic materials for chronic tissue repair.

由于缺氧和再生信号持续不足，糖尿病慢性伤口仍然难以治疗。虽然活体生物疗法为局部氧合治疗提供了一条很有前途的途径，但目前的方法主要支持单一的微生物功能，而不是与再生线索协调微生物氧合。在这里，我们报道了一种水凝胶活性治疗材料，其中交联透明质酸基质协调了长聚球菌的活代谢模块和富血小板血浆（PRP）的再生模块。该基质具有可注射性和快速凝胶性，同时支持微生物代谢活性，调节prp衍生生长因子的局部保留和释放。由此产生的材料维持氧气的产生，并保持生活舱的生存能力。特别是，它可以减少细胞内ROS的积累，促进成纤维细胞的迁移，并促进内皮管的形成。在糖尿病伤口中，它能加速伤口愈合，改善再上皮化、胶原重塑和血管生成。转录组学分析进一步揭示了刺激反应、免疫相关、细胞因子和趋化因子相关途径的协调调节。这项工作建立了一个活的治疗材料框架，将微生物氧合与再生信号结合起来，用于病理性伤口微环境重塑。重要意义：糖尿病伤口很难愈合，因为受损组织经常缺乏氧气和再生信号。目前的活体创面治疗主要集中在微生物造氧，但很少协调氧气供应与生长因子介导的组织修复。本研究开发了一种可注射的活水凝胶，它将光合作用的长聚球菌与富含血小板的血浆结合在透明质酸基质中。该材料持续产生氧气，保留和释放再生因子，减少氧化应激，促进细胞迁移、血管生成、胶原重塑和伤口愈合。通过整合代谢氧合和再生信号，本研究为重塑病理性伤口微环境和设计用于慢性组织修复的活性治疗材料提供了策略。

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引用次数: 0

Revisiting the tension-free paradigm: Axially prestretched elastomeric nanofibrillar grafts restore artery-like axial biomechanics in a preclinical model 重新审视无张力范式：轴向预拉伸弹性纳米纤维移植物在临床前模型中恢复动脉样轴向生物力学。

IF 10.4 1区医学 Q1 ENGINEERING, BIOMEDICAL

Acta Biomaterialia

Pub Date : 2026-10-01 Epub Date: 2026-08-19 DOI: 10.1016/j.actbio.2026.08.031

Elizabeth Zermeno, Amanda Reke, Apurbo Kumar Paul, Barbara Batista de Oliveira, Jason MacTaggart, Kaspars Maleckis

Healthy arteries function under substantial axial prestretch (AP), the ratio of in vivo to unloaded ex vivo length. Loss of AP promotes tortuosity and disturbed hemodynamics associated with vascular pathology, yet artery-like AP has not been incorporated in vascular reconstructions, because conventional substitutes are axially stiff and cannot safely sustain physiological AP. Here, we present Axially Prestretched Elastomeric Nanofibrillar Grafts (APENGs), fabricated by ultrahigh-speed (43,000 rpm) rotational collector electrospinning of biomedical-grade polyurethane. APENGs matched native arterial axial stiffness and tolerated elastomeric elongation beyond AP = 1.5 without failure, excessive force generation, or plastic deformation, while maintaining adequate suture retention, permeability, and burst strength. In vitro, APENGs supported endothelial cytocompatibility and low hemolysis. In a bilateral swine carotid interposition model (8 grafts, two-week follow-up), experimental APENGs (nominal AP ≈ 1.5) achieved and retained elevated prestretch and reduced tortuosity relative to contralateral controls (nominal AP ≈ 1.0). Patency was 75% (prestretched) versus 100% (controls). Histology showed rapid mid-graft endothelialization, early smooth muscle ingrowth, and limited neointimal thickening near anastomoses. This study demonstrates the first synthetic graft implanted with controlled, artery-like AP, challenging the tension-free anastomosis paradigm and positioning AP as a vascular graft design lever to restore native artery biomechanics and mechanobiology.

Statement of significance

AP is an essential homeostatic state of healthy arteries that supports arterial biomechanics and mechanobiology. Reduction in AP is associated with tortuosity, disturbed flow, and maladaptive vascular responses, yet its mechanisms remain understudied. AP is absent from current grafts, which are too stiff to safely sustain physiological elongation, forcing tension-free implantation and leaving axial biomechanics unrestored. Here, we present APENGs, manufactured by ultrahigh-speed rotational electrospinning to achieve artery-like low axial stiffness. In a swine carotid interposition model, APENGs with controlled physiological AP demonstrated surgical feasibility, reduced tortuosity, biomimetic pulsatility, and early endothelialization. These findings challenge the tension-free paradigm and establish APENGs as a platform for restoring and studying AP-regulated vascular biomechanics and remodeling.

健康动脉在大量轴向预拉伸（AP）下的功能，即体内与体外长度的比值。由于传统的代用品轴向僵硬，不能安全维持生理AP，因此动脉样AP尚未被纳入血管重建中。在这里，我们提出了轴向预拉伸弹性纳米纤维移植物（APENGs），该移植物由超高速（43,000 rpm）旋转集电极静电纺丝制成的生物级聚氨酯。APENGs与原生动脉轴向刚度和AP以外的可容忍弹性伸长率匹配 = 1.5，不会出现故障、过度的力产生或塑性变形，同时保持足够的缝线保留、渗透性和破裂强度。在体外，APENGs支持内皮细胞相容性和低溶血。在双侧猪颈动脉介入模型（8个移植物，随访两周）中，相对于对侧对照（名义AP≈1.0），实验性APENGs（名义AP≈1.5）实现并保持了较高的预拉伸和降低的弯曲度。通畅度为75%（预拉伸），而100%（对照组）。组织学显示移植物中期快速内皮化，早期平滑肌长入，吻合口附近有限的内膜增厚。本研究展示了第一个植入可控的动脉样AP的合成移植物，挑战了无张力吻合模式，并将AP定位为血管移植物设计的基础，以恢复原生动脉的生物力学和力学生物学。意义声明：轴向预拉伸（AP）是健康动脉必不可少的稳态状态，支持动脉生物力学和力学生物学。AP减少与弯曲、血流紊乱和血管反应不良有关，但其机制仍未得到充分研究。目前的移植物缺乏AP，它们过于僵硬，无法安全地维持生理伸长，迫使无张力植入，导致轴向生物力学无法恢复。在这里，我们提出了轴向预拉伸弹性纳米纤维移植物（APENGs），通过超高速旋转静电纺丝制造，以实现动脉样的低轴向刚度。在猪颈动脉介入模型中，具有可控生理AP的APENGs显示出手术可行性，减少扭曲，仿生脉搏和早期内皮化。这些发现挑战了无张力范式，并建立了APENGs作为恢复和研究ap调节的血管生物力学和重塑的平台。

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引用次数: 0

Biomaterial-associated factors in silicone breast implant-related pathology 生物材料相关因素在硅胶乳房植入物相关病理中的作用。

IF 10.4 1区医学 Q1 ENGINEERING, BIOMEDICAL

Acta Biomaterialia

Pub Date : 2026-10-01 Epub Date: 2026-08-20 DOI: 10.1016/j.actbio.2026.08.039

Neal I Callaghan, Robin Lake, Lauren Fong-Hollohan, Kyle Medd, Christian Rempe, Michael Bezuhly, Locke Davenport Huyer

Silicone breast implants (SBIs) are among the most common surgically-implantable medical devices, but carry high complication rates, especially in the setting of post-oncologic breast reconstruction. These complications include capsular contracture, malposition, rupture, and breast implant-associated anaplastic large cell lymphoma. The development of SBI-associated complications is recognized to be multifactorial with the underlying mechanisms being poorly defined. Physical factors implicated in pathophysiology include gross mechanical stresses induced by the implant on surrounding tissue, the dissipation of friction stresses to local tissue by implant microtopography, and the incongruity of stiffness between local breast tissue, fibrous capsular tissue, and biomaterial, causing a significant gradient at the interface. Hypotheses of implicated (bio)chemical factors include direct adjuvant activity of the silicone material, the adsorption and persistence of pro-inflammatory factors at the interface, and the seeding of bacterial colonies. The current review explores in detail the physiology of the specific foreign body response to implanted materials associated with clinical SBIs, including the available evidence implicating both physical and chemical factors in the propagation of pathology. New advances in models and materials-based approaches to assessing and mitigating material-induced pathology are also reviewed. Finally, recommendations for SBI design, as well as further mechanistic work to address the pathophysiology underlying SBI-associated complications are outlined.

Statement of significance

Treatment for breast cancer is associated with significant morbidity between surgical, radiotherapeutic, and systemic therapeutic approaches. Silicone breast reconstructive devices can allow for patients to regain confidence and personal efficacy after the trauma of cancer treatment. However, these devices are notorious for immune-mediated foreign body reactions, and patients can then suffer from painful or disfiguring fibrosis, and rarely a subtype of lymphoma or whole-body autoimmune reactions. Despite the ubiquity of these devices, the pathophysiological mechanisms underlying these complications are poorly understood. In this review, we review both clinical and fundamental approaches to understanding the development of pathology related to breast reconstructive devices, and discuss potential physicochemical approaches to device composition that may minimize these risks in the future.

硅胶乳房植入物（sbi）是最常见的外科植入医疗器械之一，但其并发症发生率很高，特别是在肿瘤后乳房重建的情况下。这些并发症包括包膜挛缩、错位、破裂和乳房植入物相关的间变性大细胞淋巴瘤。sbi相关并发症的发展被认为是多因素的，其潜在机制尚不明确。病理生理学中涉及的物理因素包括植入物对周围组织产生的总机械应力，植入物微地形对局部组织摩擦应力的耗散，以及局部乳房组织、纤维包膜组织和生物材料之间刚度的不一致，导致界面处出现明显的梯度。涉及化学因素的假设包括有机硅材料的直接佐剂活性，界面上促炎因子的吸附和持久性以及细菌菌落的播种。目前的综述详细探讨了与临床sbi相关的植入材料的特定异物反应的生理学，包括物理和化学因素在病理传播中的现有证据。在模型和基于材料的方法来评估和减轻材料引起的病理的新进展也进行了回顾。最后，概述了SBI设计的建议，以及进一步解决SBI相关并发症的病理生理学机制工作。意义声明：乳腺癌的治疗与手术、放疗和全身治疗方法的显著发病率相关。硅胶乳房重建装置可以让患者在癌症治疗创伤后恢复信心和个人效能。然而，这些装置因免疫介导的异物反应而臭名昭著，患者随后可能遭受痛苦或毁容的纤维化，很少出现淋巴瘤亚型或全身自身免疫反应。尽管这些装置无处不在，但这些并发症的病理生理机制尚不清楚。在这篇综述中，我们回顾了临床和基础方法来理解与乳房重建装置相关的病理发展，并讨论了可能在未来将这些风险降到最低的装置成分的潜在物理化学方法。

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引用次数: 0

Bone regeneration, tendon fiber formation, and angiogenesis are enhanced by the multifaceted effects of biodegradable octacalcium phosphate and gelatin scaffold materials 可生物降解的磷酸八钙和明胶支架材料的多方面作用增强了骨再生、肌腱纤维形成和血管生成。

IF 10.4 1区医学 Q1 ENGINEERING, BIOMEDICAL

Acta Biomaterialia

Pub Date : 2026-10-01 Epub Date: 2026-02-21 DOI: 10.1016/j.actbio.2026.02.041

Osamu Suzuki, Yu Mori, Ryo Hamai, Ryuichi Kanabuchi, Takahisa Anada, Eiji Itoi, Toshimi Aizawa

The concept is highly attractive from the perspective of biomaterials science and tissue engineering: if a single material can act diversely on several cell types, promoting the regeneration of their respective tissues. The studies have shown that octacalcium phosphate (OCP) activates various bone-related cells, including osteoblasts, osteocytes, osteoclasts, mesenchymal stem/stromal cells, macrophages, myoblasts, tendon stem/progenitor cells, and endothelial cells. It is known that OCP (Ca₈H₂(PO₄)₆·5H₂O) cannot be sintered while maintaining its single crystal phase due to the inclusion of a large amount of water molecules. The brittleness of OCP and its handling property, however, can be improved by utilizing tissue-derived polymers such as gelatin as a matrix material. OCP/gelatin composite, in fact, enhances transcortical standardized bone defect repair in rat femur, rotator cuff tendon insertion (enthesis) in rabbit, and angiogenesis prior to bone regeneration in rat critical-sized calvaria defect. The undecalcified tissue histomorphometry of the rat femur transcortical defect found that OCP/gelatin implantation induced woven bone formation, which is a precursor of mineralized bone formation, compared to a highly porous resorbable material, β-tricalcium phosphate (β-TCP). This study investigates the multifaceted effects of OCP by focusing on its activating effects on cells derived from several different bone-related tissues.

Statement of significance

The regeneration of tissues, including bone and enthesis, is being vigorously pursued using a combination of cells, growth factors, and biomaterials, yet it continues to be a significant challenge. OCP has been advocated as a precursor of bone apatite crystals and has recently been recognized as a promising osteoconductive and biodegradable biomaterial that has attracted attention. Since OCP has been shown to exhibit pleiotropic cell activation capabilities across several cell types, proposing a new principle in biomaterials science would be possible if OCP-based materials prove effective in the regeneration of multiple tissues. This review article summarizes the multifaceted cellular activity and tissue regenerative capacities, including enthesis and vascularization, as well as new bone formation using OCP, particularly in combination with gelatin, a thermal denaturation product of collagen.

从生物材料科学和组织工程的角度来看，这个概念是非常有吸引力的：如果一种材料可以不同地作用于几种细胞类型，促进其各自组织的再生。研究表明，八磷酸钙（OCP）可激活多种骨相关细胞，包括成骨细胞、骨细胞、破骨细胞、间充质干细胞/基质细胞、巨噬细胞、成肌细胞、肌腱干/祖细胞和内皮细胞。已知OCP （Ca8H2(PO4)6·5H2O）由于含有大量的水分子，在保持其单晶相的情况下无法烧结。然而，OCP的脆性及其处理性能可以通过使用组织衍生的聚合物（如明胶）作为基质材料来改善。事实上，OCP/明胶复合材料可以促进大鼠股骨经皮质标准化骨缺损修复，兔肌腱套插入（终端），以及大鼠临界尺寸颅骨缺损骨再生前的血管生成。大鼠股骨经皮质缺损的未钙化组织形态测量发现，与高多孔可吸收材料β-磷酸三钙（β-TCP）相比，OCP/明胶植入诱导编织骨形成，这是矿化骨形成的前体。本研究通过关注OCP对来自几种不同骨相关组织的细胞的激活作用，探讨了OCP的多方面作用。意义声明：组织的再生，包括骨和髋部，正在大力追求使用细胞，生长因子和生物材料的组合，但它仍然是一个重大的挑战。八钙磷酸钙（OCP）作为骨磷灰石晶体的前体，近年来被认为是一种很有前途的骨导电性和可生物降解的生物材料，引起了人们的关注。由于OCP已被证明具有跨多种细胞类型的多效性细胞激活能力，如果OCP基材料在多种组织再生中被证明有效，那么在生物材料科学中提出一个新的原理将是可能的。本文综述了OCP的多方面细胞活性和组织再生能力，包括终端化和血管化，以及新骨形成，特别是与明胶（胶原蛋白的热变性产物）结合使用。

{"title":"Bone regeneration, tendon fiber formation, and angiogenesis are enhanced by the multifaceted effects of biodegradable octacalcium phosphate and gelatin scaffold materials","authors":"Osamu Suzuki, Yu Mori, Ryo Hamai, Ryuichi Kanabuchi, Takahisa Anada, Eiji Itoi, Toshimi Aizawa","doi":"10.1016/j.actbio.2026.02.041","DOIUrl":"10.1016/j.actbio.2026.02.041","url":null,"abstract":"<div><div>The concept is highly attractive from the perspective of biomaterials science and tissue engineering: if a single material can act diversely on several cell types, promoting the regeneration of their respective tissues. The studies have shown that octacalcium phosphate (OCP) activates various bone-related cells, including osteoblasts, osteocytes, osteoclasts, mesenchymal stem/stromal cells, macrophages, myoblasts, tendon stem/progenitor cells, and endothelial cells. It is known that OCP (Ca<sub>8</sub>H<sub>2</sub>(PO<sub>4</sub>)<sub>6</sub>·5H<sub>2</sub>O) cannot be sintered while maintaining its single crystal phase due to the inclusion of a large amount of water molecules. The brittleness of OCP and its handling property, however, can be improved by utilizing tissue-derived polymers such as gelatin as a matrix material. OCP/gelatin composite, in fact, enhances transcortical standardized bone defect repair in rat femur, rotator cuff tendon insertion (enthesis) in rabbit, and angiogenesis prior to bone regeneration in rat critical-sized calvaria defect. The undecalcified tissue histomorphometry of the rat femur transcortical defect found that OCP/gelatin implantation induced woven bone formation, which is a precursor of mineralized bone formation, compared to a highly porous resorbable material, β-tricalcium phosphate (β-TCP). This study investigates the multifaceted effects of OCP by focusing on its activating effects on cells derived from several different bone-related tissues.</div></div><div><h3>Statement of significance</h3><div>The regeneration of tissues, including bone and enthesis, is being vigorously pursued using a combination of cells, growth factors, and biomaterials, yet it continues to be a significant challenge. OCP has been advocated as a precursor of bone apatite crystals and has recently been recognized as a promising osteoconductive and biodegradable biomaterial that has attracted attention. Since OCP has been shown to exhibit pleiotropic cell activation capabilities across several cell types, proposing a new principle in biomaterials science would be possible if OCP-based materials prove effective in the regeneration of multiple tissues. This review article summarizes the multifaceted cellular activity and tissue regenerative capacities, including enthesis and vascularization, as well as new bone formation using OCP, particularly in combination with gelatin, a thermal denaturation product of collagen.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"224 ","pages":"Pages 4-19"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277969","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}

引用次数: 0

Hard tissue organoids: From concept to practice 硬组织类器官：从概念到实践。

IF 10.4 1区医学 Q1 ENGINEERING, BIOMEDICAL

Acta Biomaterialia

Pub Date : 2026-10-01 Epub Date: 2026-04-12 DOI: 10.1016/j.actbio.2026.04.014

Xueqian Xu, Weijie Zhang, Jiayao Qian, Xinchen Gu, Suna Fan, Qianqian Niu, Rui L. Reis, Subhas C. Kundu, Xiang Yao, Yaopeng Zhang

Hard tissues are core components maintaining the mechanical integrity and physiological functions of organisms but have limited self-repair capacity. Traditional clinical strategies for hard tissue healing or regeneration face challenges, including donor scarcity. As engineered 3D cell culture systems that recapitulate tissue/organ-specific structures and functions, organoids outperform conventional 2D cell culture systems and animal models, thereby holding substantial potential for hard tissue healing or regeneration. Regrettably, constructing desired hard tissue organoids is highly demanding, as simulating the intricate structures and mechanical properties of native hard tissues is inherently challenging. Recently, hard tissue organoids have gradually transformed from a conceptual framework into tangible research objects. Focusing on this challenging yet promising field, this review comprehensively delineates the desired features and corresponding viewpoints of hard tissue organoids. It then systematically summarizes the design and construction strategies for organoids, the specific advances in hard tissue organoid development, and their diverse biomedical applications. Furthermore, contemporary challenges and prospective directions in the development and translational application of hard tissue organoids are thoroughly discussed. The summarized insights and proposed perspectives aim to guide the design and engineering of next-generation, or even ideal hard tissue organoids. This review may further facilitate the widespread application and efficient use of hard tissue organoids, as well as related advanced matrix technologies, in drug screening and hard tissue regeneration.

Statement of Significance

As engineered 3D systems recapitulating tissue/organ-specific structures and functions, organoids outperform conventional 2D cell cultures and animal models. Regrettably, constructing desired hard tissue organoids remains demanding, as simulating the intricate structures and superior mechanical properties of native hard tissues is inherently challenging. Focused on this promising field, this review comprehensively outlines the desired features and corresponding viewpoints of hard tissue organoids. It also summarizes the design and construction strategies for organoids, the latest advances in hard tissue organoid development, and their diverse biomedical applications. Finally, current challenges and prospective directions in their development and translational application are thoroughly discussed, with a focus on multidimensional biomimicry, simulation of typical gradient features, and integrated assembly of adjacent tissue organoids.

硬组织是维持机体机械完整性和生理功能的核心部件，但其自我修复能力有限。硬组织愈合或再生的传统临床策略面临挑战，包括供体稀缺。作为概括组织/器官特异性结构和功能的工程化3D细胞培养系统，类器官优于传统的2D细胞培养系统和动物模型，因此在硬组织愈合或再生方面具有巨大潜力。遗憾的是，构建所需的硬组织类器官要求很高，因为模拟天然硬组织的复杂结构和力学特性本身就具有挑战性。近年来，硬组织类器官逐渐从概念框架转变为有形的研究对象。针对这一具有挑战性但前景广阔的领域，本文综述了硬组织类器官的期望特征和相应的观点。然后系统地总结了类器官的设计和构建策略，硬组织类器官发展的具体进展及其在生物医学上的广泛应用。并对硬组织类器官的发展和转化应用面临的挑战和未来发展方向进行了深入讨论。总结的见解和提出的观点旨在指导下一代，甚至理想的硬组织类器官的设计和工程。本文综述将进一步促进硬组织类器官及其相关先进基质技术在药物筛选和硬组织再生方面的广泛应用和有效利用。意义声明：作为工程3D系统概括组织/器官特异性结构和功能，类器官优于传统的2D细胞培养和动物模型。遗憾的是，构建理想的硬组织类器官仍然是艰巨的，因为模拟天然硬组织的复杂结构和优越的机械性能本身就是一个挑战。针对这一前景广阔的领域，本文综述了硬组织类器官的研究特点及相关观点。综述了类器官的设计与构建策略、硬组织类器官的最新进展及其在生物医学上的广泛应用。最后，深入讨论了其发展和转化应用的当前挑战和未来方向，重点讨论了多维仿生学、典型梯度特征模拟和相邻组织类器官的集成组装。

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引用次数: 0

Doxorubicin-induced Cardiotoxicity is Propagated by Paracrine Signaling through Small Extracellular Vesicles 阿霉素诱导的心脏毒性通过细胞外小泡通过旁分泌信号传播。

IF 10.4 1区医学 Q1 ENGINEERING, BIOMEDICAL

Acta Biomaterialia

Pub Date : 2026-10-01 Epub Date: 2026-08-28 DOI: 10.1016/j.actbio.2026.08.049

George Ronan, Lara Ece Celebi, Nicole Kowalczyk, Noor Behnam, Lauren Hawthorne, Jun Yang, Frank Ketchum, Aoife J. Lowery, Michael J. Kerin, Pinar Zorlutuna

Cardiovascular disease (CVD) is the leading cause of death worldwide. Chemotherapy-induced CVD is increasingly recognized as a contributor to long-term morbidity in cancer survivors. Doxorubicin (DOX) is a widely used chemotherapeutic to treat breast cancer, one of the most common cancers in the United States. However, over 10% of treated women experience acute cardiotoxicity immediately following treatment, and approximately 2% develop severe cardiotoxicity up to 10 years after treatment, yet the mechanisms driving this delayed onset remain unclear. Here, we show that DOX treatment of cardiac cells changes their function and paracrine signaling profile. Subsequent exposure of healthy cells to altered extracellular vesicles (EVs) recapitulates the effects of direct DOX exposure in 2D/3D in vitro models, suggesting a mechanism for propagating initial injury. Plasma-EV miRNA profiling of blinded patient samples revealed distinct clustering by DOX-cardiotoxicity risk, with high-risk patients exhibiting miRNA signatures similar to those from DOX-treated models. Pathway analysis of miRNAs linked them to cardiac homeostasis and cardiotoxicity-related mechanisms, supporting the potential of plasma-EV miRNAs as noninvasive biomarkers for early risk stratification and personalized cardioprotective interventions in oncological care, and targeting of key miRNA clusters to enhance understanding of and intervention strategies for preventing the onset of DOX cardiotoxicity.

Statement of significance

Doxorubicin is an effective chemotherapy drug, but its use is limited by cardiotoxicity that can appear during treatment or years later. The mechanisms driving this delayed injury remain poorly understood. In this study, we show for the first time that small EVs released from doxorubicin-treated human cardiac cells can propagate doxorubicin-like dysfunction to healthy human cardiac cells even in the absence of the drug itself. We further identify broad miRNA cargo changes in these EVs and show that related EV-associated miRNA shifts are also detectable in patient plasma. These findings provide new mechanistic insight into anthracycline cardiotoxicity and highlight EV-associated miRNAs as promising candidates for minimally invasive diagnosis and future therapeutic intervention.

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引用次数: 0

Preconditioned endothelialized grafts reduce stenosis and improve vascular remodeling in a rat pulmonary artery model 预处理内皮化移植物在大鼠肺动脉模型中减少狭窄和改善血管重塑。

IF 10.4 1区医学 Q1 ENGINEERING, BIOMEDICAL

Acta Biomaterialia

Pub Date : 2026-10-01 Epub Date: 2026-08-20 DOI: 10.1016/j.actbio.2026.08.038

Wei Zhang, Qinzhe Xing, Séverine Ménoret, Ignacio Anegon, Yibing Qyang

Pulmonary artery reconstruction is frequently required for congenital heart disease repair, yet current graft options remain limited by the scarcity of autologous conduits and the poor durability of synthetic grafts, which often fail due to thrombosis, stenosis, and calcification. Challenges are exacerbated in the hypoxic, low-pressure pulmonary circulation. Because a functional endothelium is critical for preventing thrombosis and neointimal hyperplasia, we engineered ready-to-use endothelialized tissue-engineered vascular grafts (TEVGs) using a stepwise shear-preconditioning regimen that mimics physiological pulmonary hemodynamics. Human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) were seeded onto decellularized vascular grafts and conditioned under pulsatile shear stress before implantation. Shear-preconditioned endothelialization improved graft compliance, reduced fibrinogen absorption, and increased endothelial resistance to hypoxic stress in vitro. We then evaluated graft performance in a rat pulmonary artery transplantation model designed to recapitulate the hypoxic and stenosis-prone environment of congenital heart disease. Shear-preconditioned endothelialized grafts maintained patency for one month, supported host cell repopulation, and promoted macrophage-mediated remodeling, whereas all control grafts developed severe stenosis. Patent grafts preserved lung alveolar architecture, while stenotic grafts resulted in exudative lung injury. These findings suggest that shear-preconditioned endothelialization may represent a strategy to generate functional vascular grafts for pulmonary artery reconstruction and establish a physiologically relevant small-animal platform for evaluating TEVG performance in congenital heart diseases.

Statement of significance

Limited graft availability and the lack of functional endothelial layer remain key factors contributing to stenosis and graft failure in pulmonary artery reconstruction. Here, we reported development of an endothelialized tissue-engineered vascular graft (TEVG) generated through physiological shear-stress preconditioning to promote endothelial maturation and functional adaptation to the hypoxic, low-pressure pulmonary environment. To evaluate graft performance under physiologically relevant condition, we established a reproducible rat left pulmonary artery transplantation model. Compared with control grafts that developed severe stenosis, shear-preconditioned endothelialized TEVGs maintained luminal patency and showed graft recellularization at one month after implantation. This work presents a shear-preconditioned endothelialization strategy to enhance graft patency and remodeling for pulmonary circulation reconstruction in a physiologically relevant small animal model.

先天性心脏病的修复通常需要肺动脉重建，但目前的移植物选择仍然受到自体导管的缺乏和合成移植物耐久性差的限制，这些移植物经常因血栓形成、狭窄和钙化而失败。在低氧、低压的肺循环中，挑战会加剧。由于功能内皮对于预防血栓形成和新生内膜增生至关重要，我们设计了现成的内皮化组织工程血管移植物（TEVGs），采用逐步剪切预处理方案，模拟生理肺血流动力学。将人诱导多能干细胞来源的内皮细胞（iPSC-ECs）植入去细胞血管移植物，并在植入前进行脉动剪切应力调节。剪切预处理内皮化改善移植物顺应性，减少纤维蛋白原吸收，并增加内皮对体外缺氧应激的抵抗力。然后，我们在一个大鼠肺动脉移植模型中评估了移植物的性能，该模型旨在重现先天性心脏病的缺氧和狭窄易发环境。剪切预处理的内皮化移植物维持通畅一个月，支持宿主细胞再生，促进巨噬细胞介导的重塑，而所有对照移植物均出现严重狭窄。不通畅的移植物保留了肺泡结构，而狭窄的移植物导致肺渗出性损伤。这些研究结果表明，剪切预处理内皮化可能代表了一种产生功能性血管移植物用于肺动脉重建的策略，并建立了一个生理相关的小动物平台来评估TEVG在先天性心脏病中的表现。意义声明：有限的移植物可用性和缺乏功能性内皮层仍然是导致肺动脉重建中狭窄和移植物失败的关键因素。在这里，我们报道了一种内皮化组织工程血管移植物（TEVG）的发展，该血管移植物通过生理剪切应力预处理产生，以促进内皮成熟和对缺氧，低压肺环境的功能适应。为了评价移植体在生理相关条件下的性能，我们建立了可重复的大鼠左肺动脉移植模型。与发生严重狭窄的对照移植物相比，剪切预处理的内皮化TEVGs在植入后1个月保持管腔通畅并显示移植物再细胞化。这项工作提出了一种剪切预处理内皮化策略，以增强移植物的通畅和重塑，从而在生理相关的小动物模型中重建肺循环。

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引用次数: 0