Bioprinted biomimetic hydrogel matrices guiding stem cell aggregates for enhanced chondrogenesis and cartilage regeneration

Yuetian Liu; Lijuan Du; Hua Zhang; Guanrong Li; Yang Luo; Zeming Hu; Rong Xu; Jie Yao; Zheyuan Shi; Yige Chen; Chi Zhang; Zhanping Jin; Caihua Zhang; Chanchan Xie; Jun Fu; Yabin Zhu; Yingchun Zhu

doi:10.1039/D4TB00323C

Bioprinted biomimetic hydrogel matrices guiding stem cell aggregates for enhanced chondrogenesis and cartilage regeneration†

Yuetian Liu,‡^ab Lijuan Du,‡^b Hua Zhang,*^bd Guanrong Li,^ab Yang Luo,

^ab Zeming Hu,^b Rong Xu,^ab Jie Yao,^a Zheyuan Shi,^ab Yige Chen,^b Chi Zhang,^a Zhanping Jin,^a Caihua Zhang,^a Chanchan Xie,^a Jun Fu,

*^c Yabin Zhu

*^b and Yingchun Zhu*^a

Author affiliations

* Corresponding authors

^a The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China
E-mail: fyyzhuyingchun@nbu.edu.cn

^b Research Institute of Smart Medicine and Biological Engineering, Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, China
E-mail: zhanghua@nbu.edu.cn, zhuyabin@nbu.edu.cn

^c Key Laboratory of Polymeric Composite and Functional Materials of Ministry of Education, Guangdong Engineering Technology Research Centre for Functional Biomaterials, School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou, China
E-mail: fujun8@mail.sysu.edu.cn

^d State Key Laboratory of Molecular Engineering of Polymers (Fudan University), Shanghai 200438, China

Abstract

Articular cartilage tissue has limited self-repair capabilities, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously. Herein, this work reports a bioprintable hydrogel matrix with high cellular adhesion and aggregation properties for cartilage repair. The hydrogel comprises an enhanced cell-adhesive gelatin methacrylate and a cell-cohesive chitosan methacrylate (CHMA), both of which are subjected to photo-initiated crosslinking. By precisely adjusting the CHMA content, the mechanical stability and biochemical cues of the hydrogels are finely tuned to promote cellular aggregation, chondrogenic differentiation and cartilage repair implantation. Multi-layer constructs encapsulated with BMSCs, with high cell viability reaching 91.1%, are bioprinted and photo-crosslinked to support chondrogenic differentiation for 21 days. BMSCs rapidly form aggregates and display efficient chondrogenic differentiation both on the hydrogels and within bioprinted constructs, as evidenced by the upregulated expression of Sox9, Aggrecan and Collagen 2a1 genes, along with high protein levels. Transplantation of these BMSC-laden bioprinted hydrogels into cartilaginous defects demonstrates effective hyaline cartilage repair. Overall, this cell-responsive hydrogel scaffold holds immense promise for applications in cartilage tissue engineering.

This article is part of the themed collection: Journal of Materials Chemistry A, B & C 10th Anniversary Perspectives

Journal of Materials Chemistry B

Bioprinted biomimetic hydrogel matrices guiding stem cell aggregates for enhanced chondrogenesis and cartilage regeneration†

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Bioprinted biomimetic hydrogel matrices guiding stem cell aggregates for enhanced chondrogenesis and cartilage regeneration

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