刺激响应高分子水凝胶微球的制备及骨组织工程应用研究进展

杜晨曦; 王冉冉; 魏刚

doi:10.14028/j.cnki.1003-3726.2026.26.088

您当前的位置：

首页 >

文章列表页 >

刺激响应高分子水凝胶微球的制备及骨组织工程应用研究进展

综述 | 更新时间：2026-07-13

- 刺激响应高分子水凝胶微球的制备及骨组织工程应用研究进展
- Research Progress and Tissue Engineering Applications of Stimuli-responsive Polymer Hydrogel Microspheres
- 高分子通报 2026年
- 作者机构：
  
  青岛科技大学高分子科学与工程学院　青岛 266042
  青岛大学化学化工学院　青岛 266071
- 作者简介：
  
  wei-lab@qust.edu.cn
- 基金信息：
  
  山东省泰山学者项目(tsqn201909104);青岛科技大学高层次人才启动基金
- DOI：10.14028/j.cnki.1003-3726.2026.26.088
  中图分类号：
- 收稿：2026-02-26，
  
  录用：2026-04-22，
- 稿件说明：
移动端阅览
杜晨曦, 王冉冉, 魏刚. 刺激响应高分子水凝胶微球的制备及骨组织工程应用研究进展. 高分子通报, doi: 10.14028/j.cnki.1003-3726.2026.26.088

Du, C. X.; Wang, R. R.; Wei, G. Research progress and tissue engineering applications of stimuli-responsive polymer hydrogel microspheres. Polym. Bull. (in Chinese), doi: 10.14028/j.cnki.1003-3726.2026.26.088
杜晨曦, 王冉冉, 魏刚. 刺激响应高分子水凝胶微球的制备及骨组织工程应用研究进展. 高分子通报, doi: 10.14028/j.cnki.1003-3726.2026.26.088 DOI：

Du, C. X.; Wang, R. R.; Wei, G. Research progress and tissue engineering applications of stimuli-responsive polymer hydrogel microspheres. Polym. Bull. (in Chinese), doi: 10.14028/j.cnki.1003-3726.2026.26.088 DOI：

摘要

刺激响应高分子水凝胶微球作为一种兼具结构可设计性与动态调控能力的功能材料，在骨缺损修复、骨质疏松治疗、骨髓炎抗感染及骨关节炎调控等骨组织工程方面展现出重要应用潜力。本文围绕刺激响应高分子水凝胶微球的材料体系与结构设计，系统综述了其主要类型(温度、pH、光及多重刺激响应)及其响应机理，重点梳理了乳液法、喷雾法、微流控等微球构筑策略及其结构调控方法。在此基础上，归纳总结了其在骨缺损修复、抗感染调控及成骨促进等生物医学工程方面的应用进展，并从功能整合与作用机制角度进行分类分析。进一步讨论了当前存在的关键问题，包括响应精度不足、体内环境适配性有限以及结构稳定性与功能协同之间的矛盾。最后，对多刺激协同响应、结构精细化设计及临床转化方向的发展趋势进行了展望。

Abstract

Stimuli-responsive polymer hydrogel microspheres

as functional materials with tunable structures and dynamic regulatory capabilities

have demonstrated significant potential in bone tissue engineering

including applications in bone defect repair

osteop

orosis treatment

anti-infection therapy for osteomyelitis

and osteoarthritis regulation. This review focuses on the material systems and structural design of stimuli-responsive polymer hydrogel microspheres. The main categories

including temperature-

pH-

light-

and multi-responsive systems

and their underlying mechanisms are systematically summarized. Particular emphasis is placed on microsphere fabrication strategies

such as emulsion

spray

and microfluidic methods

and their structural regulation approaches. On this basis

recent advances in their biomedical engineering applications

including bone defect repair

anti-infection regulation

and osteogenesis promotion

are comprehensively reviewed and classified from the perspectives of functional integration and mechanisms of action. Furthermore

the current challenges are discussed

including limited response precision

insufficient adaptability to complex

in vivo

environments

and trade-offs between structural stability and functional performance. Finally

future perspectives are proposed

highlighting multi-stimuli synergistic systems

refined structural designs

and clinical translation.

关键词

Keywords

references

Gu, G. H. ; Xu, Y. Y. ; He, P. ; Li, C. X. ; Chen, S. Q. ; Wei, G. ; Xi, Y. M . Bioinspired composite hydrogels with osteogenic, angiogenic, and antioxidant properties for enhanced bone repair . Small Struct. , 2025 , 6 ( 4 ), 2400462 .

Gu, G. H. ; Chen, X. ; Wei, G. ; Xu, M. J . MXene-reinforced bioactive polymer hydrogels for biomedical applications . APL Mater. , 2024 , 12 ( 8 ), 080602 .

Gu, G. H. ; Cui, Z. C. ; Du, X. F. ; He, P. ; Rong, C. ; Tao, H. ; Wei, G. ; Xi, Y. M . Recent advances in biomacromolecule-reinforced 2D material (2DM) hydrogels: from interactions, synthesis, and functionalization to biomedical applications . Adv. Funct. Mater. , 2024 , 34 ( 48 ), 2408367 .

Sun, Z. G. ; Hu, H. Q. ; Xu, Y. Y. ; Zhang, X. C. ; Zheng, L. J. ; Sun, Z. J. ; Xiao, Y. F. ; Dong, F. ; Wei, G. ; Zhang, X. F . Neurophilic peptide-reinforced dual-fiber-network bioactive hydrogels for spinal cord injury repair . Chem. Eng. J. , 2024 , 498 , 155301 .

Sun, Z. G. ; Sun, Z. J. ; Du, C. X. ; Chen, H. Y. ; Zhang, X. C. ; Liu, Y. Y. ; Dong, F. ; Ma, X. X. ; Wei, G. ; Yue, H. Y . Frog-derived neuroregenerative-peptide-reinforced bioactive hydrogels with injectability, thermosensitivity, and enhanced neurotrophic function for repairing central nervous injuries . Small Struct. , 2025 , 6 ( 7 ), 2400572 .

Zhao, Z. ; Dong, P. ; Wang, H. C. ; Su, J. B. ; Yu, M. H. ; Shi, H. Y. ; Gao, T. Q. ; Zhang, Q. ; Chen, W. Z. ; Yang, J. Y. ; Zhang, H. J. ; Wei, Y. L . Hydrogel-based microspheres for intra-articular osteoarthritis therapy: multifunctional carriers for drug delivery and cartilage repair: a comprehensive review . Int. J. Nanomed. , 2025 , 20 , 10795 – 10813 .

Luan, X. ; Hu, H. Q. ; Zhu, D. Z. ; He, P. ; Sun, Z. G. ; Xi, Y. M. ; Wei, G . Injectable chitosan hydrogels doped with 2D peptide nanosheet-drug conjugates for glutathione-responsive sustained drug delivery . Chem. , 2024 , 30 ( 28 ), e202400021 .

Mu, R. Q. ; Gu, G. H. ; Xu, Y. Y. ; Xi, Y. M. ; Wei, G . Photo-stimulating dual-network microminiature hydrogels reinforced with silver sulfide nanoparticles for regulated cancer photothermal therapy . Chem. Eng. J. , 2025 , 510 , 161836 .

Wang, Z. H. ; Li, X. X. ; Jiang, Y. P. ; Wu, T. Y. ; Guo, S. J. ; Li, T . Preparation of hydrogel microsphere and its application in articular cartilage injury . Mater. Today Bio , 2025 , 31 , 101641 .

Chen, J. Y. ; Deng, M. C. ; Wang, J. L. ; Liu, Y. W. ; Hu, Z. R. ; Luan, F. F. ; Zhu, H. F. ; Zheng, C. X . Recent advances in injectable hydrogels for osteoarthritis treatments . Front. Bioeng. Biotechnol. , 2025 , 13 , 1644222 .

Radjabian, M. ; Abetz, V . Advanced porous polymer membranes from self-assembling block copolymers . Prog. Polym. Sci. , 2020 , 102 , 101219 .

Zhang, Y. L. ; Wu, B. M . Current advances in stimuli-responsive hydrogels as smart drug delivery carriers . Gels , 2023 , 9 ( 10 ), 838 .

Yilmaz, A. S. ; Pepe, A. ; Latifi, N. ; Sawyer, G. W. ; Dunne, M. R . Stimuli-responsive hydrogels in targeted cancer therapy: a systematic review of materials, mechanisms, and delivery strategies . Mater. Des. , 2026 , 261 , 115318 .

Zhang, M. Z. ; Gu, G. H. ; Xu, Y. Y. ; Luan, X. ; Liu, J. Y. ; He, P. ; Wei, G . Injectable self-healing antibacterial hydrogels with tailored functions by loading peptide nanofiber-biomimetic silver nanoparticles . Macromol. Rapid Commun. , 2024 , 45 ( 16 ), 2400173 .

Yadav, J. ; Chahal, S. ; Kumar, P. ; Kumar, C . Thermo-responsive smart hydrogels: molecular engineering, dynamic cross-linking strategies, and therapeutics applications . Gels , 2026 , 12 ( 1 ), 12 .

Gao, K. ; Xu, K . Advancements and prospects of pH-responsive hydrogels in biomedicine . Gels , 2025 , 11 ( 4 ), 293 .

Xin, H. ; Abdullah Al Maruf, D. S. ; Akin-Ige, F. ; Amin, S . Stimuli-responsive hydrogels for skin wound healing and regeneration . Emergent Mater. , 2025 , 8 ( 3 ), 1339 – 1356 .

Maity, S. ; Mahata, K. ; Meshram, B. ; Banerjee, S . Smart polymer-derived injectable hydrogels: current status and future perspectives . ACS Polym. Au , 2025 , 5 ( 6 ), 680 – 711 .

Neumann, M. ; di Marco, G. ; Iudin, D. ; Viola, M. ; van Nostrum, C. F. ; van Ravensteijn, B. G. P. ; Vermonden, T . Stimuli-responsive hydrogels: the dynamic smart biomaterials of tomorrow . Macromolecules , 2023 , 56 ( 21 ), 8377 – 8392 .

Okihara, M. ; Matsuda, A. ; Kawamura, A. ; Miyata, T . Design of dual stimuli-responsive gels with physical and chemical properties that vary in response to light and temperature and cell behavior on their surfaces . Polym. J. , 2024 , 56 ( 3 ), 193 – 204 .

Nunziata, G. ; Pollonio, D. ; Lacroce, E. ; Rossi, F . Smart pH-responsive polymers in biomedical applications: nanoparticles, hydrogels, and emerging hybrid platforms . Mater. Today Chem. , 2025 , 49 , 103063 .

Roy, A. ; Manna, K. ; Pal, S . Recent advances in various stimuli-responsive hydrogels: from synthetic designs to emerging healthcare applications . Mater. Chem. Front. , 2022 , 6 ( 17 ), 2338 – 2385 .

Yu, H. Y. ; Gao, R. Y. ; Liu, Y. X. ; Fu, L. M. ; Zhou, J. ; Li, L. Y . Stimulus-responsive hydrogels as drug delivery systems for inflammation targeted therapy . Adv. Sci. , 2024 , 11 ( 1 ), 2470004 .

Protsak, I. S. ; Morozov, Y. M . Fundamentals and advances in stimuli-responsive hydrogels and their applications: a review . Gels , 2025 , 11 ( 1 ), 30 .

Lv, T. Y. ; Chen, Y. Z. ; Li, N. ; Liao, X. Y. ; Heng, Y. M. ; Guo, Y. Y. ; Hu, K. J . A comprehensive review of thermosensitive hydrogels: mechanism, optimization strategies, and applications . Gels , 2025 , 11 ( 7 ), 544 .

Santoni, S. ; Mauri, E. ; Repossini, L. ; Briatico Vangosa, F. ; Colosimo, B. M. ; Sponchioni, M. ; Moscatelli, D . Thermoresponsive polymers with reversible sol–gel transition for 4D bioprinting . ACS Appl. Polym. Mater. , 2025 , 7 ( 4 ), 2652 – 2664 .

Belyaeva, A. A. ; Averchuk, A. S. ; Rozanova, N. A. ; Alexandrova, O. P. ; Solomakha, O. A. ; Nashchekina, Y. A. ; Korzhikov-Vlakh, V. A. ; Yurchenko, S. O. ; Salmina, A. B. ; Korzhikova-Vlakh, E. G. ; Morozova, S. M . Thermosensitive injectable fibrillar gels based on cellulose nanocrystals grafted with poly( N -isopropylacrylamide) as biocompatible brain implants . Carbohydr. Polym. , 2024 , 346 , 122596 .

Simpson, C. R. ; Kelly, H. M. ; Murphy, C. M . The design and development of an injectable thermoresponsive hydrogel for controlled simvastatin release in bone repair applications . Gels , 2025 , 11 ( 12 ), 995 .

Ghosh, S. ; Manna, K. ; Chakraborty, K. ; Dhara, S. ; Pal, S . Site-specific drug delivery using injectable pH-responsive biopolymeric hydrogel: instant crosslinking and shear thinning . ACS Appl. Polym. Mater. , 2025 , 7 ( 7 ), 4166 – 4176 .

Bazban-Shotorbani, S. ; Hasani-Sadrabadi, M. M. ; Karkhaneh, A. ; Serpooshan, V. ; Jacob, K. I. ; Moshaverinia, A. ; Mahmoudi, M . Revisiting structure-property relationship of pH-responsive polymers for drug delivery applications . J. Control. Release , 2017 , 253 , 46 – 63 .

Shi, H. L. ; Ma, D. X. ; Wu, D. ; Qiu, X. ; Yang, S. ; Wang, Y. Y. ; Xiao, L. ; Ji, X. Y. ; Zhang, W. ; Han, S. Y. ; Huo, P. F. ; Dong, J. D. ; Kong, X. Z. ; Guan, X. ; Zhang, D. W . A pH-responsive, injectable and self-healing chitosan-coumarin hydrogel based on Schiff base and hydrogen bonds . Int. J. Biol. Macromol. , 2024 , 255 , 128122 .

Li, L. ; Bai, G. ; Gu, W. J. ; Niu, C. H. ; Feng, Y. L. ; Wei, Z. ; Chen, K. ; Guo, X. H . Boronic ester bonds hydrogel with temperature and pH responsiveness for controlled release fertilizer . Ind. Crops Prod. , 2024 , 221 , 119336 .

Yang, J. ; Shen, T. ; Wei, J. H. ; Chen, C. ; Cao, W. K. ; Li, W. H . pH-responsive intrinsic self-healing coating via in-situ confined solid-liquid transition of hydrogel microdomains . npj Mater. Degrad. , 2025 , 9 , 98 .

Di Martino, M. ; Sessa, L. ; Diana, R. ; Piotto, S. ; Concilio, S . Recent progress in photoresponsive biomaterials . Molecules , 2023 , 28 ( 9 ), 3712 .

Dhand, A. P. ; Kirkpatrick, B. E. ; Garay-Sarmiento, M. ; Nelson, B. R. ; Miksch, C. E. ; Meurer-Zeman, B. ; Zlotnick, H. M. ; Mandal, A. ; Lee, J. S. ; Cione, J. ; Bowman, C. N. ; Anseth, K. S. ; Burdick, J. A . Digital light processing of photoresponsive and programmable hydrogels . Sci. Adv. , 2025 , 11 ( 32 ), eadw9262 .

Tavakkoli Fard, S. ; Thongrom, B. ; Achazi, K. ; Ma, G. X. ; Haag, R. ; Tzschucke, C. C . Photo-responsive hydrogels based on a ruthenium complex: synthesis and degradation . Soft Matter , 2024 , 20 ( 6 ), 1301 – 1308 .

Knaipp, K. ; Kargl, R. ; Makuc, D. ; Plavec, J. ; Žagar, E. ; Stana Kleinschek, K. ; Gescheidt, G . Azobri-dged dextran: a photoresponsive sustainable material with photo-tunable mechanical properties . Biomacromolecules , 2025 , 26 ( 3 ), 1737 – 1747 .

Mu, R. Q. ; Gu, G. H. ; Wang, X. Y. ; Wang, R. R. ; Wei, G . Biometallic peptide-drug conjugates in photo-crosslinkable hydrogels enable combined photothermal-chemotherapy against breast cancer . J. Nanobiotechnol. , 2026 , 24 ( 1 ), 241 .

Li, J. Y. ; Mooney, D. J . Designing hydrogels for controlled drug delivery . Nat. Rev. Mater. , 2016 , 1 , 16071 .

Rol, F. ; Belgacem, M. N. ; Gandini, A. ; Bras, J . Recent advances in surface-modified cellulose nanofibrils . Prog. Polym. Sci. , 2019 , 88 , 241 – 264 .

Suhail, M. ; Alamgir, Wahab. A. ; Eggers, T. ; Ahmad, Z. ; Shehzad, K. ; Iqbal, M. Z . Magnetically responsive hydrogel systems: fundamental features, emerging applications, and future horizons . Coord. Chem. Rev. , 2025 , 543 , 216916 .

Qi, Y. ; Wang, F. F. ; Liu, J. L. ; Wang, C. Y. ; Liu, Y . Enzyme-mediated hydrogelation for biomedical applications: a review . Int. J. Biol. Macromol. , 2025 , 311 , 143379 .

Terriac, L. ; Helesbeux, J. J. ; Maugars, Y. ; Guicheux, J. ; Tibbitt, M. W. ; Delplace, V . Boronate ester hydrogels for biomedical applications: challenges and opportunities . Chem. Mater. , 2024 , 36 ( 14 ), 6674 – 6695 .

Mahdian, M. ; Akbari Asrari, S. ; Ahmadi, M. ; Madrakian, T. ; Rezvani Jalal, N. ; Afkhami, A. ; Moradi, M. ; Gholami, L . Dual stimuli-responsive gelatin-based hydrogel for pH and temperature-sensitive delivery of curcumin anticancer drug . J. Drug Deliv. Sci. Technol. , 2023 , 84 , 104537 .

Zhao, L. L. ; Zhou, Y. F. ; Zhang, J. Y. ; Liang, H. Z. ; Chen, X. W. ; Tan, H . Natural polymer-based hydrogels: from polymer to biomedical applications . Pharmaceutics , 2023 , 15 ( 10 ), 2514 .

Berradi, A. ; Aziz, F. ; El Achaby, M. ; Ouazzani, N. ; Mandi, L . A comprehensive review of polysaccharide-based hydrogels as promising biomaterials . Polymers , 2023 , 15 ( 13 ), 2908 .

Friday, C. ; Edgar, K . Recent developments in all-polysaccharide hydrogels: synthesis, properties, and biomedical applications . Carbohydr. Polym. , 2026 , 376 , 124806 .

Oyervides-Guajardo, V. G. ; Claudio-Rizo, J. A. ; Cabrera-Munguia, D. A. ; Cano-Salazar, L. F. ; León-Campos, M. I. ; Tamayo-Ordoñez, M. C . Protein-polysaccharide hydrogels: a review on smart materials for the future of biotechnology . Polym. Adv. Technol. , 2025 , 36 ( 8 ), e70295 .

Ahmed, M. S. ; Yun, S. A. ; Kim, H. Y. ; Ko, S. ; Islam, M. ; Nam, K. W . Hydrogels and microgels: Driving revolutionary innovations in targeted drug delivery, strengthening infection management, and advancing tissue repair and regeneration . Gels , 2025 , 11 ( 3 ), 179 .

Yang, M. ; Shi, Y. Y. ; Wang, F. ; Zhang, X. ; Shao, J. Y. ; Yang, F. ; Sun, H. ; Zhang, C. ; Zhou, Z. ; Huang, J. Y. ; Lv, P. Y. ; Yung, P. S. ; Cheng, J. ; Huang, H. J. ; Wang, J. Q . Hydrogel microspheres as versatile platforms for biomedical research: design, properties, and applications . MedComm , 2025 , 6 ( 10 ), e70423 .

Yue, J. J. ; Liu, Z. B. ; Wang, L. ; Wang, M. ; Pan, G. Q . Recent advances in bioactive hydrogel microspheres: material engineering strategies and biomedical prospects . Mater. Today Bio , 2025 , 31 , 101614 .

Li, H. Y. ; Iyer, K. S. ; Bao, L. ; Zhai, J. L. ; Li, J. J . Advances in the development of granular microporous injectable hydrogels with non-spherical microgels and their applications in tissue regeneration . Adv. Healthc. Mater. , 2024 , 13 ( 25 ), 2301597 .

Dai, W. Q. ; Luo, Y. C. ; Zhou, K. C. ; Wu, Z. L. ; Jian, X. M. ; Xu, H. ; He, W. J. ; Zhang, D. H . Microfluidics-based hydrogel microspheres: complex structure design and multidisciplinary applications . Chem. Eng. Process. Process. Intensif. , 2026 , 219 , 110595 .

Li, Y. H. ; Huang, D. Y. ; Zhang, Y. T. ; Xiao, Y. ; Zhang, X. D . Microfluidic-assisted engineering of hydrogels with microscale complexity . Acta Biomater. , 2025 , 199 , 1 – 17 .

Lin, F. ; Li, Y. H. ; Cui, W. G . Injectable hydrogel microspheres in cartilage repair . Biomed. Technol. , 2023 , 1 , 18 – 29 .

Zeng, Y. W. ; Huang, C. ; Duan, D. M. ; Lou, A. J. ; Guo, Y. ; Xiao, T. H. ; Wei, J. G. ; Liu, S. ; Wang, Z. ; Yang, Q. H. ; Zhou, L. ; Wu, Z. H. ; Wang, L . Injectable temperature-sensitive hydrogel system incorporating deferoxamine-loaded microspheres promotes H-type blood vessel-related bone repair of a critical size femoral defect . Acta Biomater. , 2022 , 153 , 108 – 123 .

Chi, H. G. ; Qiu, Y. Q. ; Ye, X. Q. ; Shi, J. L. ; Li, Z. Y . Preparation strategy of hydrogel microsphere and its application in skin repair . Front. Bioeng. Biotechnol. , 2023 , 11 , 1239183 .

Li, L. M. ; Yu, M. L. ; Li, Y. ; Li, Q. ; Yang, H. C. ; Zheng, M. ; Han, Y. ; Lu, D. ; Lu, S. ; Gui, L . Synergistic anti-inflammatory and osteogenic n-HA/resveratrol/chitosan composite microspheres for osteoporotic bone regeneration . Bioact. Mater. , 2021 , 6 ( 5 ), 1255 – 1266 .

Alnaief, M. ; Mohammad, B. ; Altarawneh, I. ; Alkhatib, D. ; Al-Hamamre, Z. ; Mashaqbeh, H. ; Bani-Melhem, K. ; Obeidat, R . Hybrid alginate-based polysaccharide aerogels microparticles for drug delivery: preparation, characterization, and performance evaluation . Gels , 2025 , 11 ( 10 ), 775 .

Di Natale, C. ; Lagreca, E. ; Panzetta, V. ; Gallo, M. ; Passannanti, F. ; Vitale, M. ; Fusco, S. ; Vecchione, R. ; Nigro, R. ; Netti, P . Morphological and rheological guided design for the microencapsulation process of lactobacillus paracasei CBA L74 in calcium alginate microspheres . Front. Bioeng. Biotechnol. , 2021 , 9 , 660691 .

Chang, K. C. ; Chang, P. J. ; Chen, J. C. ; Huang, S. M. ; Liu, S. M. ; Shih, C. J. ; Chen, W. C . In vitro characterizations of post-crosslinked gelatin-based microspheres modified by phosphatidylcholine or diammonium phosphate as antibiotic delivery vehicles . Polymers , 2023 , 15 ( 6 ), 1504 .

Demir, B. ; Hacker, M. C . Critical process parameters of gelatin microparticle fabrication with a water-in-oil emulsion method . Int. J. Pharm. , 2025 , 686 , 126302 .

Pareja Tello, R. ; Wang, S. Q. ; Fontana, F. ; Correia, A. ; Molinaro, G. ; López Cerdà, S. ; Hietala, S. ; Hirvonen, J. ; Barreto, G. ; Santos, H. A . Fabrication of hydrogel microspheres via microfluidics using inverse electron demand Diels-Alder click chemistry-based tetrazine-norbornene for drug delivery and cell encapsulation applications . Biomater. Sci. , 2023 , 11 ( 14 ), 4972 – 4984 .

Vehring, R . Pharmaceutical particle engineering via spray drying . Pharm. Res. , 2008 , 25 ( 5 ), 999 – 1022 .

Sosnik, A. ; Seremeta, K. P . Advantages and challenges of the spray-drying technology for the production of pure drug particles and drug-loaded polymeric carriers . Adv. Colloid Interface Sci. , 2015 , 223 , 40 – 54 .

Zhang, C. ; Grossier, R. ; Candoni, N. ; Veesler, S . Preparation of alginate hydrogel microparticles by gelation introducing cross-linkers using droplet-based microfluidics: a review of methods . Biomater. Res. , 2021 , 25 , 41 .

Zhang, T. ; Zhang, H. ; Zhou, W. P. ; Jiang, K. M. ; Liu, C. ; Wang, R. ; Zhou, Y. S. ; Zhang, Z. Q. ; Mei, Q. ; Dong, W. F. ; Sun, M. X. ; Li, H. W . One-step generation and purification of cell-encapsulated hydrogel microsphere with an easily assembled microfluidic device . Front. Bioeng. Biotechnol. , 2022 , 9 , 816089 .

Orabi, M. ; Lo, J. F . Emerging advances in microfluidic hydrogel droplets for tissue engineering and STEM cell mechanobiology . Gels , 2023 , 9 ( 10 ), 790 .

Fergola, A. ; Gaglio, C. G. ; Marasso, S. L. ; Cocuzza, M. ; Fabrizio Pirri, C. ; Napione, L. ; Frascella, F . Biomaterials in droplet-based microfluidics: from structural design to biomedical applications . Mater. Today Adv. , 2025 , 28 , 100667 .

Chen, Y. ; Hu, S. K. ; Wang, Z. X. ; Zhao, Y. ; Chen, Y. F. ; Qiu, X. F. ; Yang, H. ; Sun, H. Z . Microfluidic one-step fabrication of structurally tunable alginate hydrogel microspheres via multiphase shear-induced emulsification/internal gelation . Colloids Surf. A Physicochem. Eng. Aspects , 2025 , 726 , 137727 .

Wang, J. L. ; Wang, C. ; Wang, Q. ; Zhang, Z. H. ; Wang, H. ; Wang, S. Y. ; Chi, Z. C. ; Shang, L. R. ; Wang, W. Q. ; Shu, Y. L . Microfluidic preparation of gelatin methacryloyl microgels as local drug delivery vehicles for hearing loss therapy . ACS Appl. Mater. Interfaces , 2022 , 14 ( 41 ), 46212 – 46223 .

Mirshafiei, M. ; Rashedi, H. ; Yazdian, F. ; Mahmoudi, Z . Microfluidic-assisted fabrication of cell-laden GelMA/SilMA microspheres incorporated dexamethasone-loaded MSNs for promoting osteogenic differentiation . Chem. Eng. J. , 2025 , 520 , 166221 .

Lin, C. H. ; Srioudom, J. R. ; Sun, W. ; Xing, M. ; Yan, S. ; Yu, L. ; Yang, J . The use of hydrogel microspheres as cell and drug delivery carriers for bone, cartilage, and soft tissue regeneration . Biomater. Transl. , 2024 , 5 , 236 – 256 .

Hu, X. ; Zhang, M. X. ; Xu, F. W. ; Fang, Q. Q. ; Cai, J. Q. ; Chen, Y. Q. ; Ma, J. J. ; Tan, W. Q. ; Wang, Y . Preparation methods of hydrogel microspheres and recent advances in their application for treating diabetic wounds . Int. J. Nanomed. , 2025 , 20 , 10645 – 10666 .

Lei, Y. ; Santos, H. A. ; Cui, W . Advances and challenges in hydrogel microspheres for biomedical applications . Biomater. Transl. , 2024 , 5 ( 3 ), 203 – 204 .

Xiong, J. F. ; Song, X. X. ; Cai, Y. H. ; Liu, J. H. ; Li, Y. Y. ; Ji, Y. Q. ; Guo, L. ; Cheang, U. K . Stop-flow lithography for the continuous production of degradable hydrogel achiral crescent microswimmers . Micromachines , 2022 , 13 ( 5 ), 798 .

Khader, B. A. ; Waldman, S. D. ; Hwang, D. K . Immiscible phase separation-driven microfabrication of gelatin methacryloyl scaffolds for BMP-2 delivery and osteogenic enhancement . Macromol. Biosci. , 2025 , 25 ( 12 ), e00296 .

Wu, Z. H. ; Song, X. J. ; Zhang, Y. R. ; Lin, R . Injectable hydrogel loaded with electrostatic self-assembled structure nanoparticles for the treatment of inflammatory bowel disease . Adv. Compos. Hybrid Mater. , 2025 , 8 ( 5 ), 367 .

Akgonullu, D. Z. ; Murray, B. S. ; Connell, S. D. ; Fang, Y. ; Linter, B. ; Sarkar, A . Synthetic and biopolymeric microgels: review of similarities and difference in behaviour in bulk phases and at interfaces . Adv. Colloid Interface Sci. , 2023 , 320 , 102983 .

Li, J. P. ; Wei, G. T. ; Yuan, Y. H. ; Wang, L. ; Qiu, M. H. ; Li, B. ; Ma, R. F. ; Wu, J. W. ; Shen, Z. Y . New direction in antimicrobial delivery system: preparation and applications of hydrogel microspheres . Pharmaceutics , 2025 , 17 ( 4 ), 529 .

Zhang, S. H. ; Lin, A. Q. ; Tao, Z. W. ; Fu, Y. Y. ; Xiao, L. ; Ruan, G. M. ; Li, Y. L . Microsphere-containing hydrogel scaffolds for tissue engineering . Chem. , 2022 , 17 ( 20 ), e202200630 .

Li, H. H. ; Yu, L. L. ; Li, Z. ; Li, S. C. ; Liu, Y. ; Qu, G. W. ; Chen, K. ; Huang, L. Q. ; Li, Z. A. ; Ren, J. N. ; Wu, X. W. ; Huang, J. J . A narrative review of bioactive hydrogel microspheres: ingredients, modifications, fabrications, biological functions, and applications . Small , 2025 , 21 ( 25 ), 2570192 .

Chen, J. N. ; Zhou, X. F. ; Li, Y. T. ; Liu, T. ; Ding, W. G. ; He, F. ; Xu, Y . Transforming osteoarthritis treatment: embracing hydrogel microspheres . ACS Materials Lett. , 2024 , 6 ( 8 ), 3862 – 3882 .

Wu, Z. J. ; Shi, G. ; Li, L. H. ; Piao, Z. Z. ; Wang, J. W. ; Chen, R. X. ; Hao, Z. W. ; Zhang, Z. Y. ; Li, Z. W. ; Huang, Y. L. ; Li, J. F . Recent advances in smart responsive hydrogel microspheres for tissue regeneration: preparation, characteristics and applications . Mater. Horiz. , 2025 , 12 ( 21 ), 8943 – 8988 .

Yang, J. L. ; Xia, P. F. ; Meng, F. S. ; Li, X. C. ; Xu, X. Y . Bio-functional hydrogel microspheres for musculoskeletal regeneration . Adv. Funct. Mater. , 2024 , 34 ( 33 ), 2400257 .

Li, H. ; Zhao, T. Y. ; Yuan, Z. G. ; Gao, T. Z. ; Yang, Y. K. ; Li, R. M. ; Tian, Q. Y. ; Tang, P. F. ; Guo, Q. Y. ; Zhang, L. C . Cartilage lacuna-biomimetic hydrogel microspheres endowed with integrated biological signal boost endogenous articular cartilage regeneration . Bioact. Mater. , 2024 , 41 , 61 – 82 .

Chen, M. J. ; Bolognesi, G. ; Vladisavljević, G. T . Crosslinking strategies for the microfluidic production of microgels . Molecules , 2021 , 26 ( 12 ), 3752 .

Tiemeijer, B. M. ; Tel, J . Hydrogels for single-cell microgel production: recent advances and applications . Front. Bioeng. Biotechnol. , 2022 , 10 , 891461 .

Chen, S. ; Shahar, T. ; Cohen, S . Thermo-controlled microfluidic generation of monodisperse alginate microspheres based on external gelation . RSC Adv. , 2024 , 14 ( 44 ), 32021 – 32028 .

Yang, X. D. ; Xu, Y. ; Zhu, D. C. ; Mi, X. Q . GelMA core-shell microgel preparation based on a droplet microfluidic device for three-dimensional tumor ball culture and its drug testing . Molecules , 2025 , 30 ( 15 ), 3305 .

Sattari, A. ; Janfaza, S. ; Mashhadi Keshtiban, M. ; Tasnim, N. ; Hanafizadeh, P. ; Hoorfar, M . Microfluidic on-chip production of alginate hydrogels using double coflow geometry . ACS Omega , 2021 , 6 ( 40 ), 25964 – 25971 .

Cheng, L. ; Lu, Y. Z. ; Li, P. Y. ; Sun, B. G. ; Wu, L. D . Metal-organic framework (MOF)-embedded magnetic polysaccharide hydrogel beads as efficient adsorbents for malachite green removal . Molecules , 2025 , 30 ( 7 ), 1560 .

Zhang, Y. Q. ; Shi, Z. P. ; Shu, Y. M. ; Shafiq, M. ; Lan, Z. Y. ; Liang, X. ; Ma, M. ; Chen, H. R . Cerium nanozyme-powered hydrogel microspheres alleviate thromboangiitis obliterans via enhanced stem cell therapy . Small , 2025 , 21 ( 20 ), 2408748 .

Chen, X. Y. ; Ren, L. ; Zhang, H. ; Hu, Y. N. ; Liao, M. H. ; Shen, Y. B. ; Wang, K. C. ; Cai, J. Y. ; Cheng, H. ; Guo, J. M. ; Qi, Y. R. ; Wei, H. ; Li, X. K. ; Shang, L. R. ; Xiao, J. ; Sun, J. W. ; Chai, R. J . Basic fibroblast growth factor-loaded methacrylate gelatin hydrogel microspheres for spinal nerve regeneration . Smart Med. , 2023 , 2 ( 2 ), e20220038 .

Zheng, J. H. ; Li, C. R. ; Zhang, Q. X. ; Ou, T. ; Li, L. L. ; Yu, P. F. ; Wei, S. J. ; Hou, G. G. ; Yan, H. H . Bioinspired porous core-shell microspheres with spatiotemporal delivery coordinate immunomodulatory-osteogenic coupling via NF-κB/P-STAT6 and Rho/MAPK signaling for enhanced calvarial regeneration . Bioact. Mater. , 2025 , 54 , 103 – 125 .

Ai, Y. X. ; Hu, C. P. ; Wang, Y. F. ; Liu, Y. J. ; Liu, R. F. ; Xu, H. L. ; Li, H. ; Zhao, Y. Q. ; Wang, Y. H. ; Ning, R. J. ; Ju, C. ; Wu, W. D. ; Chen, X. B. ; He, S. Y. ; Wang, Z. Y. ; Luo, R. J. ; Huang, D. G. ; Hao, D. J. ; Zhu, L . Core-shell hydrogel microspheres with sequential delivery of cerium oxide nanoparticles and spinal white matter extracellular matrix for improved functional recovery in spinal cord injury . Chem. Eng. J. , 2025 , 508 , 160861 .

Hu, X. L. ; Hu, Q. X. ; Liu, S. H. ; Zhang, H. G . Synergy of engineered gelatin methacrylate-based porous microspheres and multicellular assembly to promote osteogenesis and angiogenesis in bone tissue reconstruction . Int. J. Biol. Macromol. , 2024 , 283 , 137228 .

Daly, A. C . Granular hydrogels in biofabrication: recent advances and future perspectives . Adv. Healthc. Mater. , 2024 , 13 ( 25 ), 2301388 .

Ou, Y. T. ; Cao, S. X. ; Zhang, Y. ; Zhu, H. J. ; Guo, C. Z. ; Yan, W. ; Xin, F. X. ; Dong, W. L. ; Zhang, Y. L. ; Narita, M. ; Yu, Z. Y. ; Knowles, T. P. J . Bioprinting microporous functional living materials from protein-based core-shell microgels . Nat. Commun. , 2023 , 14 , 322 .

Molley, T. G. ; Hung, T. T. ; Kilian, K. A . Cell-laden gradient microgel suspensions for spatial control of differentiation during biofabrication . Adv. Healthc. Mater. , 2022 , 11 ( 24 ), 2201122 .

Bektas, C. ; Mao, Y . Hydrogel microparticles for bone regeneration . Gels , 2024 , 10 ( 1 ), 28 .

Chen, L. H. ; Li, J. L. ; Tu, S. W. ; Yang, S. S. ; Lei, Y. X. ; Wang, L. L. ; Shi, X. N. ; Yang, J. M. ; Li, X. H . Injectable hydrogel microspheres for osteoarthritis therapy via endogenous mesenchymal stem cells homing and chondrogenic differentiation enhancement . Adv. Healthc. Mater. , 2025 , 15 : e04727 .

Zhu, Z. L. ; Luo, Y. J. ; Xiao, P. C. ; Xie, Y. ; Zhang, J. ; Huang, K. ; Wu, X. D. ; Lu, K. ; Zhang, Y. T. ; Tan, J. Y. ; Chen, H. ; Huang, W. ; Lei, Y. T. ; Liao, J. Y . Carrier rocket-inspired hydrogel microspheres targeting subchondral bone osteoclast activity alleviate osteoarthritic pain and cartilage degeneration . J. Nanobiotechnol. , 2025 , 23 ( 1 ), 551 .

Seliktar, D . Designing cell-compatible hydrogels for biomedical applications . Science , 2012 , 336 ( 6085 ), 1124 – 1128 .

Li, Y. L. ; Rodrigues, J. ; Tomás, H . Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications . Chem. Soc. Rev. , 2012 , 41 ( 6 ), 2193 – 2221 .

Appel, E. A. ; Tibbitt, M. W. ; Webber, M. J. ; Mattix, B. A. ; Veiseh, O. ; Langer, R . Self-assembled hydrogels utilizing polymer-nanoparticle interactions . Nat. Commun. , 2015 , 6 , 6295 .

Tang, R. ; Gui, X. Y. ; Han, R. Y. ; Gao, C. Y. ; Zhang, H. ; Lu, S. K. ; Zhao, J. Y. ; Zhou, W. K. ; Chen, A. X. ; Sun, H. ; Sun, J. X. ; Zhai, Y. ; Zhao, Z. H. ; Zhou, C. C . A shape-adaptive hydrogel with dual antibacterial and osteogenic properties for alveolar bone defect repair . J. Mater. Chem. B , 2025 , 13 ( 5 ), 1712 – 1730 .

Culla, A. C. ; Vater, C. ; Tian, X. G. ; Bolte, J. ; Ahlfeld, T. ; Bretschneider, H. ; Pape, A. ; Goodman, S. B. ; Gelinsky, M. ; Zwingenberger, S . Treatment of critical size femoral bone defects with biomimetic hybrid scaffolds of 3D plotted calcium phosphate cement and mineralized collagen matrix . Int. J. Mol. Sci. , 2022 , 23 ( 6 ), 3400 .

Ma, K. X. ; Yang, L. ; Li, W. Z. ; Chen, K. ; Shang, L. R. ; Bai, Y. S. ; Zhao, Y. J . Mussel-inspired multi-bioactive microsphere scaffolds for bone defect photothermal therapy . Mater. Today Bio , 2024 , 29 , 101363 .

Xiao, P. C. ; Liu, J. Y. ; Du, C. C. ; Cheng, S. W. ; Liu, S. R. ; Liu, J. C. ; Zhan, J. D. ; Chen, Z. L. ; Yang, Y. J. ; Lei, Y. T. ; Huang, W. ; Zhao, C . Injectable mineralized hydrogel microspheres for accelerated osteocyte network reconstruction and intelligent bone regeneration . J. Control. Release , 2025 , 380 , 240 – 255 .

Patrick, M. D. ; Keys, J. F. ; Suresh Kumar, H. ; Annamalai, R. T . Injectable nanoporous microgels generate vascularized constructs and support bone regeneration in critical-sized defects . Sci. Rep. , 2022 , 12 , 15811 .

Thakur, A. ; Jaiswal, M. K. ; Peak, C. W. ; Carrow, J. K. ; Gentry, J. ; Dolatshahi-Pirouz, A. ; Gaharwar, A. K . Injectable shear-thinning nanoengineered hydrogels for stem cell delivery . Nanoscale , 2016 , 8 ( 24 ), 12362 – 12372 .

Huang, X. P. ; Chen, D. ; Liang, C. Z. ; Shi, K. S. ; Zhou, X. P. ; Zhang, Y. A. ; Li, Y. ; Chen, J. J. ; Xia, K. S. ; Shu, J. W. ; Yang, B. ; Wang, J. K. ; Xu, H. B. ; Yu, C. ; Cheng, F. ; Wang, S. K. ; Zhang, Y. X. ; Wang, C. G. ; Ying, L. W. ; Li, H. ; Han, M. L. ; Li, F. C. ; Tao, Y. Q. ; Zhao, Q. ; Chen, Q. X . Swelling-mediated mechanical stimulation regulates differentiation of adipose-derived mesenchymal stem cells for intervertebral disc repair using injectable UCST microgels . Adv. Healthc. Mater. , 2023 , 12 ( 3 ), 2201925 .

Chen, J. J. ; Yan, X. R. ; Nie, L. ; Zhou, S. Q. ; Ji, P. ; Zhang, H. M . Injectable hydrogel microsphere orchestrates immune regulation and bone regeneration via sustained release of calcitriol . Mater. Today Bio , 2025 , 32 , 101687 .

Zhang, X. T. ; Yang, B. G. ; Feng, L. ; Xu, X. Y. ; Wang, C. M. ; Lee, Y. W. ; Wang, M. ; Lu, X. ; Qin, L. ; Lin, S. E. ; Bian, L. M. ; Li, G . Augmenting osteoporotic bone regeneration through a hydrogel-based rejuvenating microenvironment . Bioact. Mater. , 2024 , 41 , 440 – 454 .

Wu, Q. J. ; Hu, L. W. ; Yan, R. ; Shi, J. F. ; Gu, H. ; Deng, Y. W. ; Jiang, R. X. ; Wen, J. ; Jiang, X. Q . Strontium-incorporated bioceramic scaffolds for enhanced osteoporosis bone regeneration . Bone Res. , 2022 , 10 , 55 .

Zhou, X. D. ; Lu, R. L. ; Jia, M. Q. ; Lai, H. J. ; Xiao, X. ; Yao, Y. C. ; Yuan, T. ; Li, P. F. ; Zhang, S. Y . Degradation-dependent self-release hydrogel with over three months of antioxidation and anti-inflammation for osteoporotic bone repair . Chem. Mater. , 2024 , 36 ( 7 ), 3381 – 3394 .

Ma, Y. Y. ; Su, H. W. ; Li, W. H. ; Mao, S. H. ; Feng, Z. H. ; Qiu, Y. ; Chen, K. ; Chen, Q. C. ; Wang, H. ; Zhu, Z. Z . The hyaluronic acid-gelatin hierarchical hydrogel for osteoporotic bone defect repairment . Int. J. Biol. Macromol. , 2024 , 276 , 133821 .

Lei, M. Y. ; Liu, H. B. ; Zhong, Q. ; Zhao, L. B. ; Liu, J. W. ; Mai, H. M. ; Zhang, Y. H. ; Wang, H. Y. ; Chen, Y. R. ; Chen, R. ; Xu, Y. X. ; Li, H. ; Wang, D. ; Gao, J. ; Zheng, S. W. ; Shi, Z. J. ; Wang, J. ; Cheng, H . Hydroxybutyl chitosan-based thermosensitive hydrogel enhanced osteoporotic bone regeneration through sustained release of alendronate and BMP-2 . Carbohydr. Polym. , 2026 , 373 , 124609 .

Masters, E. A. ; Ricciardi, B. F. ; de Mesy Bentley, K. L. ; Moriarty, T. F. ; Schwarz, E. M. ; Muthukrishnan, G . Skeletal infections: microbial pathogenesis, immunity and clinical management . Nat. Rev. Microbiol. , 2022 , 20 ( 7 ), 385 – 400 .

Kuo, C. Y. ; Lin, T. Y. ; Yeh, Y. C . Hydrogel-based strategies for the management of osteomyelitis . ACS Biomater. Sci. Eng. , 2023 , 9 ( 4 ), 1843 – 1861 .

Wu, S. D. ; Shuai, Y. ; Qian, G. W. ; Peng, S. P. ; Liu, Z. ; Shuai, C. J. ; Yang, S . A spatiotemporal drug release scaffold with antibiosis and bone regeneration for osteomyelitis . J. Adv. Res. , 2023 , 54 , 239 – 249 .

Andresen, A. K. ; Felding, M. S. ; Sacramento, M. M. A. ; Nielsen, L. H . Hydrogel-based drug delivery systems for localized eradication of bacterial biofilms: advances, challenges and future directions . J. Control. Release , 2026 , 390 , 114509 .

Wu, H. T. ; Lin, Y. H. ; Lin, Y. P. ; Deng, M. Y. ; Hou, J. H. ; Liu, D. H. ; Cui, Z. ; Guan, D. G. ; Wang, J. ; Yu, B . Ozone-delivering nanocomposite hydrogel for acute Staphylococcus aureus osteomyelitis treatment via neutrophil regulation . Chem. Eng. J. , 2024 , 489 , 151209 .

Zhang, R. ; Chen, L. ; Stehle, Y. ; Lin, M. Y. ; Wang, C. X. ; Li, Y. F. ; Huang, M. ; Li, Y. B. ; Zou, Q . Injectable gelatin microspheres for osteomyelitis treatment: osteogenic and anti-inflammatory effect . Mater. Adv. , 2023 , 4 ( 19 ), 4349 – 4368 .

Guo, J. Y. ; Shu, X. ; Yu, S. ; Guo, C. P. ; Shen, G. X. ; Chen, L. S. ; Zhou, J. Y. ; Xiao, J. W. ; Guo, H. L. ; Chen, Y. ; Zeng, Z. W. ; Wang, P . Injectable hydrogel microsphere-bomb for MRSA-infected chronic osteomyelitis . J. Control. Release , 2024 , 376 , 337 – 353 .

Li, B. ; Wang, F. ; Hu, F. Q. ; Ding, T. ; Huang, P. ; Xu, X. ; Liang, J. ; Li, C. W. ; Zhou, Q. ; Lu, M. ; Deng, L. F. ; Guo, L. ; Cui, W. G . Injectable “nano-micron” combined gene-hydrogel microspheres for local treatment of osteoarthritis . NPG Asia Mater. , 2022 , 14 , 1 .

Feng, K. ; Yu, Y. F. ; Chen, Z. S. ; Wang, F. ; Zhang, K. Q. ; Chen, H. F. ; Xu, J. ; Kang, Q. L . Injectable hypoxia-preconditioned cartilage progenitor cells-laden GelMA microspheres system for enhanced osteoarthritis treatment . Mater. Today Bio , 2023 , 20 , 100637 .

Xiang, H. L. ; Zhang, C. ; Xiong, Y. F. ; Wang, Y. ; Pu, C. Y. ; He, J. T. ; Chen, L. ; Jiang, K. ; Zhao, W. K. ; Yang, H. F. ; Wang, F. ; Li, Y. L . MMP13-responsive hydrogel microspheres for osteoarthritis treatment by precise delivery of celecoxib . Mater. Des. , 2024 , 241 , 112966 .

Wang, H. ; Li, Z. H. ; Liu, J. Q. ; Chang, H. R. ; Wang, J. C. ; Song, S. L. ; Zhao, Y. ; Zhao, X . Nanozyme-enhanced injectable hyaluronic acid-based hydrogel for the treatment of osteoarthritis . Int. J. Biol. Macromol. , 2024 , 282 , 136819 .

Miao, K. S. ; Zhou, Y. ; He, X. ; Xu, Y. ; Zhang, X. ; Zhao, H. ; Zhou, X. C. ; Gu, Q. L. ; Yang, H. L. ; Liu, X. Z. ; Huang, L. X. ; Shi, Q . Microenvironment-responsive bilayer hydrogel microspheres with gelatin-shell for osteoarthritis treatment . Int. J. Biol. Macromol. , 2024 , 261 , 129862 .

Qiu, S. N. ; Shi, Y. B. ; Zang, H. C. ; Sun, X. C. ; Wang, Q. J. ; Fu, X. L. ; Shen, H. ; Mo, F. Y. ; Zhang, Y. K. ; Chen, X. Q. ; Zhou, J. M. ; Li, L. ; Lin, G. M . Multifunctional injectable microspheres for osteoarthritis therapy via spatiotemporally modulating macrophage polarization and inflammation . npj Regen. Med. , 2024 , 9 , 22 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

3D打印技术在骨科个性化治疗中的应用

基于点击化学策略的聚合物分子刷设计、合成与应用研究进展

无醚聚芳基阴离子交换膜研究进展

深耕中原高分子领域四十载——河南大学高分子学科发展历程与现状

自修复防腐涂层