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Biomaterials. 2019 Jul;210:51-61. doi: 10.1016/j.biomaterials.2019.04.031. Epub 2019 Apr 28.

Injectable stem cell-laden supramolecular hydrogels enhance in situ osteochondral regeneration via the sustained co-delivery of hydrophilic and hydrophobic chondrogenic molecules.

Author information

1
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, PR China.
2
Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, College of Chemistry and Materials Science, Fujian Normal University, Fuzhou, 350007, PR China.
3
Orthopaedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, PR China.
4
Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, New Territories, 999077, Hong Kong, China.
5
Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, New Territories, 999077, Hong Kong, China; MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, PR China.
6
Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, New Territories, 999077, Hong Kong, China; Empa, Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Biomimetic Membranes and Textiles, Lerchenfeldstrasse 5, CH-9014 St. Gallen, Switzerland.
7
Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, 999077, Hong Kong, China.
8
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, PR China.
9
Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, 999077, Hong Kong, China. Electronic address: gangli@cuhk.edu.hk.
10
Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, New Territories, 999077, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, 518172, PR China; Center for Novel Biomaterials, The Chinese University of Hong Kong, Shatin, New Territories, 999077, Hong Kong, China. Electronic address: lbian@cuhk.edu.hk.

Abstract

Hydrogels have been widely used as the carrier material of therapeutic cell and drugs for articular cartilage repair. We previously demonstrated a unique host-guest macromer (HGM) approach to prepare mechanically resilient, self-healing and injectable supramolecular gelatin hydrogels free of chemical crosslinking. In this work, we show that compared with conventional hydrogels our supramolecular gelatin hydrogels mediate more sustained release of small molecular (kartogenin) and proteinaceous (TGF-β1) chondrogenic agents, leading to enhanced chondrogenesis of the encapsulated human bone marrow-derived mesenchymal stem cells (hBMSCs) in vitro and in vivo. More importantly, the supramolecular nature of our hydrogels allows injection of the pre-fabricated hydrogels containing the encapsulated hBMSCs and chondrogenic agents, and our data show that the injection process has little negative impact on the viability and chondrogenesis of the encapsulated cells and subsequent neocartilage development. Furthermore, the stem cell-laden supramolecular hydrogels administered via injection through a needle effectively promote the regeneration of both hyaline cartilage and subchondral bone in the rat osteochondral defect model. These results demonstrate that our supramolecular HGM hydrogels are promising delivery biomaterials of therapeutic agents and cells for cartilage repair via minimally invasive procedures. This unique capability of injecting cell-laden hydrogels to target sites will greatly facilitate stem cell therapies.

KEYWORDS:

Cartilage repair; Chondrogenic differentiation; Drug delivery; HGM hydrogel; Mesenchymal stem cells

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