A viscoelastic PEGylated poly(glycerol sebacate)-based bilayer scaffold for cartilage regeneration in full-thickness osteochondral defect

Dan Lin; Bolei Cai; Le Wang; Lisha Cai; Zihao Wang; Jirong Xie; Qian-Xin Lv; Yuan Yuan; Changsheng Liu; Steve Gf Shen

doi:10.1016/j.biomaterials.2020.120095

A viscoelastic PEGylated poly(glycerol sebacate)-based bilayer scaffold for cartilage regeneration in full-thickness osteochondral defect

Biomaterials. 2020 Sep:253:120095. doi: 10.1016/j.biomaterials.2020.120095. Epub 2020 May 6.

Authors

Dan Lin¹, Bolei Cai², Le Wang³, Lisha Cai⁴, Zihao Wang⁴, Jirong Xie⁵, Qian-Xin Lv³, Yuan Yuan⁶, Changsheng Liu⁷, Steve Gf Shen⁸

Affiliations

¹ Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, PR China; Engineering Research Center for Biomaterials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, PR China.
² Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, PR China; State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: caibolei1020@126.com.
³ State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, PR China.
⁴ Engineering Research Center for Biomaterials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, PR China.
⁵ Department of Prosthodontics, School of Stomatology, The Jiamusi University, Jiamusi, 154003, PR China.
⁶ Engineering Research Center for Biomaterials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, PR China. Electronic address: yyuan@ecust.edu.cn.
⁷ Engineering Research Center for Biomaterials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, PR China. Electronic address: liucs@ecust.edu.cn.
⁸ Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, PR China; Shanghai University of Medicine and Health Sciences, Shanghai, 201318, PR China. Electronic address: shengf@sumhs.edu.cn.

PMID: 32445809
DOI: 10.1016/j.biomaterials.2020.120095

Abstract

Defects of either articular cartilage or subchondral bone would destroy the structural integrity and functionality of the joint. Reconstruction of osteochondral defects requires difunctional scaffolds that simultaneously induce cartilage and subchondral bone morphogenesis, however, high-performance cartilage reconstructive scaffolds remain a considerable challenge. In this study, a solvent-free urethane crosslinking and spontaneous pore-forming procedure under room temperature was proposed and optimized to produce PEGylated poly(glycerol sebacate) (PEGS) scaffolds with controllable crosslinking degrees and hierarchical macro-/micro-porosities. Based on the economical and feasible preparative approach, the viscoelastic PEGS-12h with low crosslinking degree was demonstrated to significantly stimulate chondrogenic differentiation, maintain chondrocyte phenotype and enhance cartilage matrix secretion compared to elastic polymer with high crosslinking degree, emphasizing the importance of matrix viscoelasticity in cartilage regeneration. On this basis, the viscoelastic low-crosslinked PEGS-12h was combined with the well-acknowledged osteoinductive mesoporous bioactive glass (MBG) to construct a difunctional PEGS/MBG bilayer scaffold, and evaluated in a full-thickness osteochondral defect model in vivo. The PEGS/MBG bilayer scaffold successfully reconstructed well-integrated articular hyaline cartilage and its subchondral bone in 12 weeks, exhibiting extraordinary regenerative efficiency. The results indicated that the viscoelastic PEGS scaffold and PEGS/MBG bilayer scaffold proposed in this study made an excellent candidate for cartilage and osteochondral regeneration, and was expected for clinical translation in the future.

Keywords: Bilayer scaffold; Cartilage regeneration; Full-thickness articular defects; Osteochondral regeneration; Viscoelastic PEGylated poly(glycerol sebacate).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cartilage, Articular*
Decanoates
Glycerol / analogs & derivatives
Polyethylene Glycols
Polymers
Tissue Engineering
Tissue Scaffolds*

Substances

Decanoates
Polymers
poly(glycerol-sebacate)
Polyethylene Glycols
Glycerol