title: PEGylated poly(glycerol sebacate)-modified calcium phosphate scaffolds with desirable mechanical behavior and enhanced osteogenic capacity.
abstract: Calcium phosphate (CaP) scaffolds have been widely used as bone graft substitutes, but undesirable mechanical robustness and bioactivity greatly hamper its availability in clinic application. To address these issues, PEGylated poly (glycerol sebacate) (PEGS), a hydrophilic elastomer, was used to modify a model calcium phosphate cement (CPC) scaffold for bone regeneration in this study. The PEGS pre-polymer with PEG content from 0% to 40% was synthesized and was subsequently coated onto the pre-fabricated CPC scaffolds by facile infiltration and thermal-crosslink process. Compression strength and toughness of the CPC/PEGS composite scaffold (defined as CPX/Y, X referred to the PEG content in PEGS and Y referred to PEGS amount in final scaffold) were effectively tailored with increasing coating amount and PEG content, and CPX/Y exhibited an optimal compressive strength of 3.82MPa and elongation at break of 13.20%, around 5-fold and 3-fold enhancement compared to the CPC. In vitro cell experiment with BMSCs as model indicated that coating and PEG-modified synchronously facilitated cell attachment and proliferation in a dose-dependent manner. Particularly, osteogenic differentiation of BMSCs on PEGS/CPC scaffold was strongly enhanced, especially for CP20/18. Further in vivo experiments confirmed that PEGS/CPC induced promoted osteogenesis in striking contrast to CPC and PGS/CPC. Collectively, hybrids scaffolds (around 18% coating amount and PEG content from 20% to 40%) with the combination of enhanced mechanical behavior and up-regulated cellular response were optimized and PEGS/CaP scaffolds can be deemed as a desirable option for bone tissue engineering.
  
  
  
  Insufficient mechanical robustness and bioactivity still limit the availability of calcium phosphate (CaP) scaffolds in clinic application. Herein, calcium phosphate cement (CPC) scaffold, as a model CaP-matrix material, was modified with PEGylated PGS (PEGS) polymers by facile infiltration and thermal-crosslink process. Such biomimetic combination of PEGS and CaP-matrix porous scaffold was first explored, without affecting its porous structure. In this study, CPC scaffold was endowed with robust mechanical behavior and promoted bioactivity by simultaneously optimizing the amount of polymer-coating and the PEG content in PGS. In rat critical-sized calvarial defects repairing, osteogenic efficacy of PEGS/CPC further demonstrated the potential for application in bone tissue regeneration. The design concept proposed in this study might provide new insights into the development of future tissue engineering materials.
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Zihao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Haoyi
authors.initials: H
authors.lastname: Niu
authors.affiliation: Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, PR China.
authors.forename: Han
authors.initials: H
authors.lastname: Guo
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address: yyuan@ecust.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China; Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address: liucs@ecust.edu.cn.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Liu
mesh_terms: D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects; D002130:Calcium Phosphates / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D002850:Chromatography, Gel; D003432:Cross-Linking Reagents / Q000737:chemistry; D003651:Decanoates; D005990:Glycerol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D008297:Male; D008422:Materials Testing; D055595:Mechanical Phenomena; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011108:Polymers; D017207:Rats, Sprague-Dawley; D013816:Thermodynamics; D013818:Thermogravimetry; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D002130:Calcium Phosphates; D003432:Cross-Linking Reagents; D003651:Decanoates; D011108:Polymers; C469892:poly(glycerol-sebacate); D011092:Polyethylene Glycols; C020243:calcium phosphate; D000469:Alkaline Phosphatase; D005990:Glycerol
keywords: Bone tissue engineering; CaP scaffolds; Enhanced mechanical behavior; Osteogenic capacity; PEGylated PGS