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ORIGINAL RESEARCH

Thermally guided solvent-induced porous bioabsorbable microspheres: Molecular structure and performance

Zhe Zhang1# ,  Dong Zhou1# ,  Xiaoyi Tian1 ,  Muhammad Rafique2 ,  Lan Xiao3 ,  István Bányai4 ,  Yulin Li1,5* ,  Changsheng Liu1,5* ,  Junqi Qiu6*
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1 The Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Engineering Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, China
2 Precision Biomaterials and Regeneration Medicine Lab, School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
3 School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland, Australia
4 Department of Physical Chemistry, Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary
5 Wenzhou Key Laboratory of Tissue Regeneration Medical Materials, Wenzhou Institute of Shanghai University, Wenzhou, Zhejiang, China
6 Department of Intervention, Pingyang Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
BMT, 113 https://doi.org/10.12336/bmt.25.00113
Submitted: 24 July 2025 | Revised: 13 November 2025 | Accepted: 19 November 2025 | Published: 31 December 2025
© 2025 by the Author(s). Licensee Biomaterials Translational, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 (CC BY-NC-SA 4.0) (https://creativecommons.org/licenses/by-nc-sa/4.0/deed.en)
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Abstract

The microstructure of biodegradable microspheres plays a crucial role in determining their properties, particularly in drug delivery behavior and biological effects. In this study, we developed a thermally guided, solvent–emulsion protocol to produce porous microspheres without the use of porogens. We elucidated how polymer crystallinity and chain mobility dictate pore genesis. This method employs basic stirring equipment and enables the fabrication of microspheres with superior shape uniformity, making it suitable for continuous scale-up from the laboratory to industrial production. By precisely controlling the processing temperature, we produced microspheres with different morphologies, including well-defined porous structures. The structural effects of poly(caprolactone), poly(D, L-lactic acid), and poly(L-lactic acid) on microsphere morphology were systematically investigated. The results revealed distinct molecular configurations and flexibilities among these polymers. Compared to crystalline poly(L-lactic acid), amorphous poly(D, L-lactic acid) displayed a wrinkled surface, whereas the more flexible poly(caprolactone) yielded smaller pore sizes. The interconnected porous structure of the microspheres supported slower degradation by inhibiting self-catalysis, which typically accelerates the degradation process. This porous structure enabled effective loading of simvastatin and achieved sustained release, with approximately 70% of the drug released within 1 month. This study establishes a scalable, additive-free platform for programming microsphere porosity through polymer selection and processing temperature. This approach offers precise control over degradation and hydrophobic drug release, making it highly promising for injectable tissue engineering and minimally invasive therapies. Future studies should focus on exploring the in vivo performance of these microspheres in relevant therapeutic models.

Keywords
Thermally guided solvent-induced technique
Porous structure
Poly(L-lactic acid)
Poly(caprolactone)
Biodegradable microspheres
Funding
This work was supported by the Basic Science Center Program of the National Natural Science Foundation of China (No. T2288102), the Key Research Program of Henan Province (221111520200), Clinical Medical Research Special Fund Project of Zhejiang Medical Association (2022ZYC-D13), Wenzhou Major Science and Technology Project (ZY2023010, ZY2024014), Wenzhou Basic Public Welfare Scientific Research Project (Y2023146), and the Zhejiang Provincial Natural Science Foundation of China (TGY24E030007).
Conflict of interest
The authors declare no conflict of interest.
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