Bioactive Materials最新文献_第7页

Enzyme-regulated biomineralization: Biological functions and advanced biomaterials for tissue regeneration 酶调节生物矿化：组织再生的生物功能和先进生物材料

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-25 DOI: 10.1016/j.bioactmat.2025.12.041

Qing Zhao, Mingli He, Jing Shu, Yao Huang, Jin Chen, Weihua Guo

Enzyme-regulated biomineralization offers precise spatiotemporal control over tissue mineralization, overcoming key limitations of conventional regenerative therapies. This review systematically examines the underlying biological mechanisms, focusing on enzymatic regulation of phosphate metabolism, mineralization regulators, and matrix stabilization that orchestrate hierarchical mineral deposition. Organic matrices facilitate nanoconfinement-driven nucleation and spatially controlled mineralization through biochemical functionalization. These fundamental mechanisms have inspired the development of advanced enzyme-functionalized biomaterials, such as covalently immobilized hydrogels, physically entrapped nanocomposites, bioaffinity scaffolds, and stimuli-responsive 3D-printed constructs, which enable precisely tunable in situ mineralization. In clinical applications, such biomaterial systems demonstrate significant therapeutic potential, with critical-sized bone defects showing accelerated healing through biomimetic mineral-collagen alignment and enzyme-mediated enamel restoration achieving both hardness recovery and reduced secondary caries incidence. Current limitations primarily involve enzymatic stability, immunogenicity, and manufacturing scalability. Emerging solutions focus on gene-enzyme hybrid platforms and intelligent responsive systems for personalized regenerative approaches. The synergistic integration of biological principles with materials science provides a transformative foundation for developing next-generation therapeutic strategies.

酶调节的生物矿化提供了对组织矿化的精确时空控制，克服了传统再生疗法的关键限制。这篇综述系统地研究了潜在的生物学机制，重点是磷酸盐代谢的酶调节，矿化调节和基质稳定，协调分层矿物沉积。有机基质通过生化功能化促进纳米约束驱动的成核和空间控制的矿化。这些基本机制激发了先进的酶功能化生物材料的发展，如共价固定的水凝胶、物理包裹的纳米复合材料、生物亲和性支架和刺激响应的3d打印结构，它们能够精确地调节原位矿化。在临床应用中，这种生物材料系统显示出巨大的治疗潜力，通过仿生矿物质-胶原蛋白排列和酶介导的牙釉质修复，临界尺寸的骨缺损显示出加速愈合，既能恢复硬度，又能减少继发性龋齿的发生率。目前的限制主要涉及酶的稳定性、免疫原性和制造的可扩展性。新兴的解决方案集中于基因-酶混合平台和个性化再生方法的智能响应系统。生物学原理与材料科学的协同整合为开发下一代治疗策略提供了变革性的基础。

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引用次数: 0

D-peptide engineered hydrogel with dual-enzyme-ALA cascades enables multimodal oxygen modulation for self-sustaining EDT-PDT synergy 具有双酶- ala级联的d肽工程水凝胶可实现多模态氧调节，以实现自我维持的EDT-PDT协同作用

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-25 DOI: 10.1016/j.bioactmat.2025.12.037

Qi Zhang , Zhe Zheng , Yiting Zhao , Qing Wu , Chu Wu , Xiuli Wang , Xia Wang , Qigang Wang , Peiru Wang

The transformation of O₂ is primarily facilitated by the catalytic action of redox enzymes, which play a pivotal role in sustaining cellular energy metabolism and redox balance. Bioinspired by O₂ distribution and ROS regulation related to cascade biocatalytic process, a D-peptide NapG^DF^DF^DY engineered hydrogel has been constructed with encapsulated dual-enzyme superoxide (SOD) and chloroperoxidase (CPO) cascade catalytic circuit and co-assembled photosensitizer of 5-aminolevulinic acid molecules (ALA). Multimodal oxygen modulation has been conducted by the concurrent oxygen generation via SOD-catalyzed ⋅O₂⁻ dismutation and oxygen consumption for ¹O₂ production by CPO and ALA, achieving self-sustaining enzymatic dynamic therapy (EDT)-photodynamic therapy (PDT) (EDT-PDT) synergy. The endogenous cascade-amplified EDT not only enhances the ¹O₂ efficacy in exogenous PDT therapy, but the intermediate O₂ can also alleviate local neuropathic pain caused by hypoxia for safe PDT treatment. This work pioneers enzyme-mediated dynamic control of tumor redox homeostasis, establishing a new therapeutic axis between biocatalytic amplification and photodynamic processes.

O2的转化主要是通过氧化还原酶的催化作用来实现的，氧化还原酶在维持细胞能量代谢和氧化还原平衡中起着关键作用。受级联生物催化过程中O2分布和ROS调控的启发，利用双酶超氧化物（SOD）和氯过氧化物酶（CPO）级联催化回路和5-氨基乙酰丙酸分子（ALA）共组装光敏剂，构建了d肽NapGDFDFDY工程水凝胶。多模态氧调制是通过sod催化的⋅O2−突变和CPO和ALA产生1O2的耗氧同时产生氧气，实现自我维持的酶动力治疗（EDT）和光动力治疗（PDT）（EDT-PDT）协同作用。内源性级联扩增的EDT不仅增强了1O2在外源性PDT治疗中的疗效，而且中间O2还可以减轻缺氧引起的局部神经性疼痛，安全进行PDT治疗。这项工作开创了酶介导的肿瘤氧化还原稳态动态控制，在生物催化放大和光动力过程之间建立了新的治疗轴。

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引用次数: 0

Artificial Intelligence Virtual Organoids (AIVOs) 人工智能虚拟类器官

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-22 DOI: 10.1016/j.bioactmat.2025.12.030

Long Bai , Jiacan Su

Organoid platforms have reshaped in vitro human biology yet remain constrained by batch variability, sparse longitudinal readouts and barriers to scale. This review introduces Artificial Intelligence Virtual Organoids (AIVOs), also termed silicon organoids: organoid-scale digital twins instantiated in the computational space, with virtual cells-and, where appropriate, virtual organoids-serving as the minimal executable units. AIVOs fuse multimodal and longitudinal measurements into universal state representations and use virtual instruments constrained by biophysical priors to emulate assays and perturbations, while hybrid mechanistic modules (agent-based, continuum, finite-element) capture cell-cell, cell-matrix and transport dynamics. The article defines conceptual boundaries, formalizes a data-model-interaction architecture and construction strategies, and synthesizes evaluation and standardization practices. Applications span drug screening and dosing design, disease subtyping and resistance mapping, integration with organoid-on-chip systems and clinical decision support. Principal challenges include the acquisition and harmonization of high-quality longitudinal data, scalable computation and model reduction, interpretability and causal reasoning, and governance addressing privacy, safety and fairness. Virtual organoids ultimately provide a silicon-grounded, transparent and reproducible bridge between physical organoids and clinical practice, enabling high-throughput in silico experiments and active experiment design without added experimental burden and accelerating precise therapy, mechanism discovery and regulatory translation.

类器官平台已经重塑了体外人类生物学，但仍然受到批量可变性、稀疏的纵向读数和规模障碍的限制。这篇综述介绍了人工智能虚拟类器官（AIVOs），也被称为硅类器官：在计算空间中实例化的类器官尺度数字双胞胎，其中虚拟细胞和虚拟类器官作为最小的可执行单元。AIVOs将多模态和纵向测量融合到通用状态表示中，并使用受生物物理先验约束的虚拟仪器来模拟分析和扰动，而混合机制模块（基于代理的、连续体的、有限元的）捕获细胞-细胞、细胞-矩阵和运输动力学。本文定义了概念边界，形式化了数据模型交互体系结构和构建策略，并综合了评估和标准化实践。应用范围包括药物筛选和剂量设计、疾病亚型和耐药性制图、与类器官芯片系统的集成以及临床决策支持。主要挑战包括获取和协调高质量的纵向数据、可扩展计算和模型缩减、可解释性和因果推理，以及解决隐私、安全和公平问题的治理。虚拟类器官最终在物理类器官和临床实践之间提供了一个硅基、透明和可重复的桥梁，实现了高通量的硅实验和主动实验设计，而不增加实验负担，加速了精确治疗、机制发现和调控转化。

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引用次数: 0

Engineered small extracellular vesicles as bioactive materials: Integrating engineering strategies for cargo loading and targeted delivery systems 工程小细胞外囊泡作为生物活性材料：货物装载和目标递送系统的整合工程策略

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-22 DOI: 10.1016/j.bioactmat.2025.12.029

Hongtao Xu , Rui Liu , Hao Zhou , Bin Kong , Kai Shen , Tao Zhao , Xiaofeng Du , Hao Zhang , Huanghe Song , Dunming Guo , Xiaoyuan Gu , Qing Wang , Chien-Wei Lee , Guoyong Yin , Yingze Zhang , Wei Chen

Small extracellular vesicles (sEVs) are increasingly regarded as a unique class of bioactive materials whose intrinsic membrane composition and nanoscale architecture provide a versatile platform for therapeutic engineering. Rather than passive carriers, sEVs can be actively programmed through diverse strategies to achieve efficient loading, precise targeting, and functional integration with synthetic systems. Endogenous modulation of donor cells—via genetic editing, priming with bioactive glass, cytokine stimulation, or hypoxic cues—enables selective packaging of nucleic acids, proteins, and metabolites into secreted vesicles. Exogenous techniques, including electroporation, sonication, and extrusion, allow controlled incorporation of therapeutic drugs or genome-editing complexes such as CRISPR/Cas. In parallel, surface modifications based on Lamp2b-fusion scaffolds, aptamers, antibodies, and click chemistry confer tissue tropism and extend circulation time. Integration with nanomaterials, scaffolds, and microfluidic platforms further enhances stability, scalability, and reproducibility, positioning sEVs at the intersection of biology and materials science. This review highlights recent advances in engineering sEVs as programmable bioactive materials and discusses their potential to transform regenerative medicine, oncology, and precision therapeutics.

小细胞外囊泡（sev）越来越被认为是一类独特的生物活性材料，其固有的膜组成和纳米级结构为治疗工程提供了一个多功能平台。与被动载体不同，sev可以通过多种策略进行主动编程，以实现高效装载、精确定位以及与合成系统的功能集成。供体细胞的内源性调节——通过基因编辑、生物活性玻璃启动、细胞因子刺激或缺氧提示——能够选择性地将核酸、蛋白质和代谢物包装到分泌的囊泡中。外源性技术，包括电穿孔、超声和挤压，允许治疗药物或基因组编辑复合物（如CRISPR/Cas）的可控结合。同时，基于lamp2b融合支架、适体、抗体和click化学的表面修饰赋予组织亲和性并延长循环时间。与纳米材料、支架和微流控平台的集成进一步增强了sev的稳定性、可扩展性和可重复性，使其处于生物学和材料科学的交叉点。本文重点介绍了工程sev作为可编程生物活性材料的最新进展，并讨论了它们在再生医学、肿瘤学和精确治疗方面的潜力。

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引用次数: 0

Nanocatalytic magnesium osteoimplants with biodegradable self-adaptive interfaces for therapeutic repair of infected bone defects 具有可生物降解自适应界面的纳米催化镁骨植入物用于感染性骨缺损的治疗性修复

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-22 DOI: 10.1016/j.bioactmat.2025.12.018

Yuanyuan Wu , Zhe Cai , Yuling Zhang , Yufeng Zheng , Liqiong Liao , Zhaojun Jia

Infected bone defects (e.g., osteomyelitis) present a complex clinical challenge characterized by persistent biofilms, intracellular pathogens, and compromised bone regeneration. We hypothesized that a bioadaptive magnesium implant with sequential coating/substrate degradation could render staged anti-infective and pro-regenerative therapy. To this end, we engineered TNE@AHA_C implants consisting of a Mg–Zn alloy substrate functionalized with a multilayered coating: a corrosion-resistant MgF₂ underlayer, a polydopamine/polyethyleneimine adhesive interlayer, and an infection-responsive aldehyde-modified hyaluronic acid (AHA) hydrogel toplayer embedded with microbe-targeting Fe₃O₄ nanozymes (TNE). The implants demonstrated improved hydrophilicity and corrosion resistance and time-sequenced coating/substrate degradation. In infectious microenvironments, the TNE-embedded coating degraded preferentially, releasing nanozymes that catalytically generated bactericidal hydroxyl radicals to eradicate planktonic bacteria, intracellular pathogens, and biofilms, while stimulating M1 macrophage polarization for enhanced immunobactericidal activity. Subsequently, controlled substrate corrosion released bioactive ions (Mg²⁺, Zn²⁺) and H₂, which elicited M2 macrophage polarization and osteodifferentiation, while allowing favorable biocompatibility in vitro, in ovo, and in vivo. In a Staphylococcus aureus-infected rat femoral model, TNE@AHA_C effectively eliminated infection, mitigated inflammation and osteolysis, and enhanced osteoregeneration/osseointegration. This work establishes a sequential degradation-driven bioadaptive paradigm for implant-mediated microenvironment remodeling in infectious bone defects.

感染性骨缺损（如骨髓炎）呈现出复杂的临床挑战，其特征是持续的生物膜、细胞内病原体和骨再生受损。我们假设生物适应性镁植入物具有顺序涂层/底物降解可以实现分阶段抗感染和促再生治疗。为此，我们设计了TNE@AHAC植入物，该植入物由多层涂层功能化的Mg-Zn合金衬底组成：耐腐蚀的MgF2衬底，聚多巴胺/聚乙烯亚胺粘合剂中间层，感染反应醛修饰透明质酸（AHA）水凝胶，嵌入微生物靶向Fe3O4纳米酶（TNE）。植入物表现出更好的亲水性和耐腐蚀性以及按时间顺序的涂层/衬底降解。在感染性微环境中，嵌入tne的涂层优先降解，释放纳米酶，催化产生杀菌羟基自由基，消灭浮游细菌、细胞内病原体和生物膜，同时刺激M1巨噬细胞极化，增强免疫杀菌活性。随后，受控的底物腐蚀释放出生物活性离子（Mg2+、Zn2+）和H2，诱导M2巨噬细胞极化和骨分化，同时在体外、卵内和体内均具有良好的生物相容性。在金黄色葡萄球菌感染的大鼠股骨模型中，TNE@AHAC有效消除感染，减轻炎症和骨溶解，增强骨再生/骨整合。这项工作为感染性骨缺损中植入物介导的微环境重塑建立了一个顺序降解驱动的生物适应范式。

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引用次数: 0

Microenvironment-mediated stem cell fate in periodontal tissue remodeling and repair 微环境介导的干细胞命运在牙周组织重塑和修复中的作用

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-22 DOI: 10.1016/j.bioactmat.2025.12.025

Jin-Xuan Zheng , Han Yin , Guang-Zhao Tian , Zi-Feng Quan , Zhi-Li Dong , Wen-Qian Ding , Zeng-Xuan Wang , Yu-Ting Niu , Quan-Yi Guo , Yi-Qi Tang , Wei-Min Guo

The cellular microenvironment is an integrated complex of the extracellular matrix, cells and extracellular fluids containing numerous bioactive molecules. It is widely acknowledged that the periodontal microenvironment exerts profound effects on adjacent stem cells, affecting tissue remodeling and repair. For instance, the physiological microenvironment maintains stemness and supports tissue-specific differentiation of mesenchymal stem cells (MSCs), whereas pathological inflammation resets programmed cell fate, increases the secretion of proinflammatory factors, and may even induce MSC apoptosis. The normal remodeling or repair process is therefore dysregulated, and inflammatory conditions worsen. Modulating the stem cell-based microenvironment appears to be an effective strategy for periodontal regeneration. In this review, five types of MSCs involved in periodontal tissue remodeling and repair are introduced. Subsequently, we discuss the impact of various periodontal microenvironments on MSC fate and further summarize the latest biomaterials for use in periodontal regeneration from the aspect of microenvironmental cues. The use of multiple material design strategies to modify the inflammatory microenvironment offers valuable insights for future advancement of material-guided periodontal regeneration under pathological conditions.

细胞微环境是细胞外基质、细胞和含有大量生物活性分子的细胞外液的综合复合体。人们普遍认为牙周微环境对邻近干细胞具有深远的影响，影响组织的重塑和修复。例如，生理微环境维持干细胞的干性并支持间充质干细胞（MSCs）的组织特异性分化，而病理性炎症重置程序性细胞命运，增加促炎因子的分泌，甚至可能诱导间充质干细胞凋亡。正常的重塑或修复过程因此失调，炎症状况恶化。调节干细胞微环境似乎是牙周再生的有效策略。本文就参与牙周组织重塑和修复的5种间充质干细胞进行综述。随后，我们讨论了各种牙周微环境对MSC命运的影响，并从微环境线索方面进一步总结了最新的用于牙周再生的生物材料。使用多种材料设计策略来改变炎症微环境，为病理条件下材料引导牙周再生的未来发展提供了有价值的见解。

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引用次数: 0

Hydrogel-based tumor embolization and synergistic therapeutic strategies 基于水凝胶的肿瘤栓塞及协同治疗策略

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-20 DOI: 10.1016/j.bioactmat.2025.12.031

Yisheng Peng , Xiuyi Wu , Hui Liu , Fengyi Yang , Xu Cheng , Mengmeng Miao , Shangqing Chen , Kaifei Yan , Hui Zheng , Hongwei Cheng , Gang Liu

Hydrogels, characterized by their porous network structures and microenvironment-responsive properties, have been widely explored for tumor embolization. Physically or dynamically crosslinked hydrogels-such as ionic, hydrogen-bonded, or supramolecular systems-exhibit favorable microcatheter injectability and shear-thinning behavior, whereas covalently crosslinked systems are typically delivered as low-viscosity precursors for in situ gelation. These features endow embolic hydrogels with tunable drug delivery capacity and excellent biocompatibility, enabling precise occlusion of tumor-feeding arteries and controlled, localized therapeutic release. This review uniquely emphasizes the innovative design of multifunctional hydrogels, focusing on their role in synergistic multimodal therapies and personalized cancer treatment. It provides a comprehensive overview of the latest advancements in the preparation methods and functional properties of embolic hydrogels, alongside their emerging clinical applications. Additionally, we address the challenges hindering clinical translation and propose future directions, including the personalized design of intelligent hydrogels and the exploration of synergistic mechanisms for multimodal therapeutic strategies. This review offers valuable insights into the design, development, and clinical application of embolic hydrogels for precision medicine.

水凝胶具有多孔网络结构和微环境响应特性，被广泛用于肿瘤栓塞。物理或动态交联的水凝胶（如离子、氢键或超分子体系）表现出良好的微导管注射性和剪切减薄行为，而共价交联的水凝胶通常作为原位凝胶的低粘度前体输送。这些特性使栓塞水凝胶具有可调节的药物输送能力和优异的生物相容性，能够精确阻断肿瘤供血动脉并控制局部治疗释放。这篇综述特别强调了多功能水凝胶的创新设计，重点介绍了它们在协同多模式治疗和个性化癌症治疗中的作用。它提供了一个全面的概述，在制备方法和栓塞水凝胶的功能特性的最新进展，以及他们的新兴临床应用。此外，我们解决了阻碍临床翻译的挑战，并提出了未来的方向，包括智能水凝胶的个性化设计和探索多模式治疗策略的协同机制。本文综述为精准医疗栓塞水凝胶的设计、开发和临床应用提供了有价值的见解。

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引用次数: 0

Anisotropic mechanotransductive tissue constructs via brush-assisted bioprinting of microfiber-reinforced composite bioinks 通过微纤维增强复合生物墨水的刷辅助生物打印构建各向异性机械转导组织

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-19 DOI: 10.1016/j.bioactmat.2025.12.017

Pei Mohan , ByungJoon Choi , Dogeon Yoon , GeunHyung Kim

Engineering aligned musculoskeletal and cardiac tissues remains a key challenge due to the lack of mechanical cues in conventional bioinks. Here, we present a synergistic strategy combining fiber-reinforced collagen bioinks with a brush-assisted bioprinting (BAB) process to fabricate highly organized, functional tissue constructs. The bioink incorporates straight and coiled poly(ε-caprolactone) (PCL) microfibers to deliver spatially defined biophysical guidance, while the BAB process applies directional and homogeneous shear stress to align both fibers and cells during printing. This integrated approach enhances cytoskeletal organization and activates mechanosensitive pathways, including YAP/TAZ and PIEZO1, promoting myogenic differentiation. In vitro, printed bioconstructs using C2C12 and H9C2 exhibited improved cell alignment, gene expression, and structural maturation. In a murine volumetric muscle loss (VML) model, BAB-fabricated human adipose-stem cell (hASC)-laden constructs restored muscle mass and function more effectively than control, with the coiled fiber group showing the significantly meaningful levels of muscle regeneration, reduced fibrosis, and human cell integration. Based on these results, this work can demonstrate a new platform for fabricating anisotropic tissue constructs and offer significant potential for translational applications in regenerative medicine.

由于传统的生物墨水缺乏机械线索，工程对齐肌肉骨骼和心脏组织仍然是一个关键的挑战。在这里，我们提出了一种协同策略，将纤维增强胶原蛋白生物墨水与刷辅助生物打印（BAB）工艺相结合，以制造高度组织化，功能性的组织结构。生物链接采用直的和卷曲的聚（ε-己内酯）（PCL）微纤维来提供空间定义的生物物理指导，而BAB工艺在打印过程中应用定向和均匀的剪切应力来对齐纤维和细胞。这种综合方法增强了细胞骨架组织，激活了包括YAP/TAZ和PIEZO1在内的机械敏感通路，促进了肌源性分化。在体外，使用C2C12和H9C2打印的生物构建物表现出更好的细胞排列、基因表达和结构成熟。在小鼠体积性肌肉损失（VML）模型中，bab制造的装载人类脂肪干细胞（hASC）的构建物比对照组更有效地恢复了肌肉质量和功能，卷曲纤维组显示出显著的肌肉再生水平，减少了纤维化和人类细胞整合。基于这些结果，这项工作可以展示一个制造各向异性组织结构的新平台，并为再生医学的转化应用提供了巨大的潜力。

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引用次数: 0

Control of immunogenic responses of microorganism-synthesized biopolymers for 3D bioprinting tissue engineering and regenerative medicine 用于生物3D打印、组织工程和再生医学的微生物合成生物聚合物的免疫原性反应控制

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-19 DOI: 10.1016/j.bioactmat.2025.12.008

Amitava Bhattacharyya , Insup Noh

Different biopolymers are synthesized by diverse microorganisms through cell and genetic engineering for their applications to organoids, tissue engineering, and regenerative medicine with advanced technologies such as 3D bioprinting, microfluidics, and others. All living bodies repair or replenish their tissues, organs, and systems by synthesizing different biopolymers secreted into their extracellular matrix. Microbially synthesized biopolymers have an advantage over the bulk-synthesized ones due to precise control over the synthesis process, resulting in a tunable molecular structure, molecular weight, and other important properties. This provides an edge over traditional biomaterials as immunomodulatory during tissue engineering. For clinical applications of tissue engineering, the employed biopolymers should be of medical grade with controlled immunogenic responses during and after their implantation, offering precision fabrication of tissue engineering scaffolds and adequate functional tissue regeneration by replacing the scaffolds with their matching biodegradation rates. This review focuses on control of immunogenic responses caused by microorganism-synthesized biopolymers in their applications to 3D bioprinting and other tissue engineering modalities. The synthesis, fermentation, and purification processes of microbial biopolymers and their applications in 3D bioprinted tissue engineering are explained in brief for different exopolysaccharides, proteins, polypeptides, and polyesters. The contents are focused on the preparation of medical-grade polymers, their limited chemical uses, and green and sustainable approaches for the functionalization of polymers and hydrogels in tissue engineering. The immunogenic responses (mostly innate), strategies to control them, and related advantages and concerns are mainly discussed in detail, targeting their successful clinical implementation in the 3D bioprinting-based and other tissue regeneration and reconstruction domains.

不同的生物聚合物是由不同的微生物通过细胞和基因工程合成的，用于类器官、组织工程和再生医学等先进技术，如3D生物打印、微流体等。所有生物体都通过合成分泌到细胞外基质中的不同生物聚合物来修复或补充其组织、器官和系统。微生物合成的生物聚合物由于对合成过程的精确控制，具有优于本体合成的优势，从而具有可调的分子结构、分子量和其他重要特性。这在组织工程中提供了优于传统生物材料的免疫调节优势。对于组织工程的临床应用，所使用的生物聚合物应该是医疗级的，在植入过程中和植入后的免疫原性反应应该是可控的，可以精确制造组织工程支架，并通过替换与之匹配的生物降解率的支架来提供足够的功能性组织再生。本文综述了微生物合成生物聚合物在生物3D打印和其他组织工程模式中的应用所引起的免疫原性反应的控制。微生物生物聚合物的合成、发酵和纯化过程及其在3D生物打印组织工程中的应用简要地解释了不同的外多糖、蛋白质、多肽和聚酯。内容集中在医用级聚合物的制备，其有限的化学用途，以及绿色和可持续的途径为功能化的聚合物和水凝胶在组织工程。主要详细讨论了免疫原性反应（主要是先天的），控制它们的策略，以及相关的优势和关注，目标是它们在基于3D生物打印和其他组织再生和重建领域的成功临床实施。

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引用次数: 0

Mossy-textured hydroxyapatite-modified poly (lactic-co-glycolic acid) microspheres promote collagen regeneration via calcium/TGF-β and chemokine signaling pathways in soft tissue augmentation 苔藓结构羟基磷灰石修饰聚乳酸-羟基乙酸微球通过钙/TGF-β和趋化因子信号通路促进软组织增强中的胶原再生

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-19 DOI: 10.1016/j.bioactmat.2025.12.028

Dongbiao Chang , Lili Cao , Lulu Han , Zhenfan Bai , Zili Guo , Yi Wang , Yan Zheng , Jun Sheng , Huan Tan , Xingyu Chen , Feilun Ye , Tailin Guo , Jie Weng

Skin aging resulting from collagen loss induced by endogenous and exogenous stimuli has become an important factor affecting skin aesthetics and quality of life. The use of simple and efficient soft tissue fillers represents an effective approach to promote collagen regeneration and restore soft tissue support. In this study, mossy-textured hydroxyapatite (CaHA)-modified poly (lactic-co-glycolic acid) (PLGA) composite microspheres (CaHA/PLGA) are developed. These microspheres feature a uniform and stable coating of CaHA beads on the surface of PLGA microspheres and possess particle sizes suitable for soft tissue filling (30–60 μm). The CaHA beads impart a highly porous structure, enhanced protein adsorption, and delayed degradation properties to the composite microspheres. Due to the surface modification by CaHA beads, CaHA/PLGA microspheres exhibit improved cell adhesion, proliferation, and low inflammatory response, as well as enhanced collagen deposition. In vivo studies show that, compared to commercial PLLA microspheres, CaHA/PLGA microspheres provide tissue support as long as 12 weeks with degradation stability, and significantly promote collagen network formation, supporting their long-lasting filling performance. Transcriptome sequencing indicates that CaHA/PLGA microspheres enhance calcium/TGF-β and chemokine signaling pathways in adipose-derived stem cells, facilitating cell migration, cytokine production, and extracellular collagen deposition. Overall, mossy-textured CaHA/PLGA microspheres provide a promising new strategy for soft tissue augmentation and reconstruction.

内源性和外源性刺激导致的胶原蛋白流失导致的皮肤老化已成为影响皮肤美观性和生活质量的重要因素。使用简单高效的软组织填充物是促进胶原蛋白再生和恢复软组织支持的有效途径。本研究开发了苔藓结构羟基磷灰石(CaHA)-改性聚乳酸-羟基乙酸（PLGA）复合微球（CaHA/PLGA）。这些微球具有在PLGA微球表面均匀稳定地包裹CaHA珠层的特点，具有适合软组织填充的粒径（30-60 μm）。CaHA珠赋予复合微球高度多孔结构，增强蛋白质吸附和延迟降解特性。由于CaHA微珠的表面修饰，CaHA/PLGA微球表现出更好的细胞粘附、增殖和低炎症反应，并增强胶原沉积。体内研究表明，与商业PLLA微球相比，CaHA/PLGA微球提供长达12周的组织支持，降解稳定，并显著促进胶原网络的形成，支持其持久的填充性能。转录组测序表明，CaHA/PLGA微球增强脂肪源性干细胞中的钙/TGF-β和趋化因子信号通路，促进细胞迁移、细胞因子产生和细胞外胶原沉积。综上所述，苔藓结构的CaHA/PLGA微球为软组织增强和重建提供了一种有前景的新策略。

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引用次数: 0