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RESEARCH ARTICLE

Spatiotemporal delivery of BMP-2 and FGF-18 in 3D-bioprinted tri-phasic osteochondral scaffolds enhanced compartmentalized osteogenic and chondrogenic differentiation of mesenchymal stem cells isolated from rats with varied organizational morphologies

Weiwei Su1,2 ,  Shiyu Li1,3 ,  Panjing Yin1,3 ,  Weihan Zheng1,3 ,  Ling Wang4 ,  Zhuosheng Lin1 ,  Ziyue Li1,3 ,  Zi Yan1,3 ,  Yaobin Wu1* ,  Chong Wang5* ,  Wenhua Huang1,2,3*
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1 Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
2 Department of Orthopedics, Affiliated Hospital of Putian University, Putian University, Putian, Fujian, China
3 The Third Affiliated Hospital of Southern Medical University, Guangdong Medical Innovation Platform for Translation of 3D Printing Application, Southern Medical University, Guangzhou, Guangdong, China
4 Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, China
5 Department of Intelligent Manufacturing Engineering, School of Mechanical Engineering, Dongguan University of Technology, Songshan Lake, Dongguan, Guangdong, China
IJB 2024, 10(5), 3229 https://doi.org/10.36922/ijb.3229
Submitted: 21 March 2024 | Accepted: 13 May 2024 | Published: 2 July 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Replicating the heterogeneous structure and promoting compartmentalized osteogenesis/chondrogenesis are critical considerations in designing scaffolds for osteochondral tissue regeneration. However, desirable osteochondral regeneration cannot be achieved mainly due to the absence of effective delivery strategies for growth factors (GFs) and the insufficiency of desirable organizational morphologies for seed cells. Herein, we developed a tri-phasic osteochondral scaffold consisting of bone morphogenetic protein-2 (BMP-2)-loaded subchondral layer, fibroblast growth factor-18 (FGF-18)-loaded cartilage layer, and an interface layer that acted as a barrier to reduce the mutual interference of GFs, via cryogenic 3D bioprinting. BMP-2 could exert osteogenic effects for 14 days, and FGF-18 could exert chondrogenic effects for 21 days, demonstrating the time-controlled release function of BMP-2 and FGF-18. By further seeding discrete rat bone marrow mesenchymal stem cells (rBMSCs) and rBMSC microspheres, respectively, onto the subchondral layer and cartilage layer, the engineered cell-laden osteochondral tissue was constructed. The spatiotemporal release of BMP-2 and FGF-18 in the subchondral layer and cartilage layer promoted the osteogenic differentiation of discrete rBMSCs and chondrogenic differentiation of rBMSC microspheres in the subchondral layer and cartilage layer, respectively. In summary, by seeding rBMSCs with varied organizational morphologies in 3D-printed osteochondral scaffolds with a spatiotemporally controlled strategy, engineered osteochondral tissue with compartmentalized osteogenic/chondrogenic differentiation potent can be formed, displaying a facile and promising way to achieve desirable osteochondral tissue regeneration.

Keywords
3D printing
Growth factor
Controlled release
Cell microspheres
Osteochondral regeneration
Osteogenic/chondrogenic differentiation
Funding
This work was supported by the National Key R&D Program of China (2022YFB4600600), the National Natural Science Foundation of China (32271181 and 82300018), the Guangdong Basic and Applied Basic Research Foundation (2021A1515111074), the Department of Education of Guangdong Province, China (2021ZDZX2014), the Dongguan Science and Technology of Social Development Program, Guangdong, China (20211800904542).
Conflict of interest
The authors declare no conflicts of interest.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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