title: Injectable biodegradable hybrid hydrogels based on thiolated collagen and oligo(acryloyl carbonate)-poly(ethylene glycol)-oligo(acryloyl carbonate) copolymer for functional cardiac regeneration.
abstract: Injectable biodegradable hybrid hydrogels were designed and developed based on thiolated collagen (Col-SH) and multiple acrylate containing oligo(acryloyl carbonate)-b-poly(ethylene glycol)-b-oligo(acryloyl carbonate) (OAC-PEG-OAC) copolymers for functional cardiac regeneration. Hydrogels were readily formed under physiological conditions (37°C and pH 7.4) from Col-SH and OAC-PEG-OAC via a Michael-type addition reaction, with gelation times ranging from 0.4 to 8.1 min and storage moduli from 11.4 to 55.6 kPa, depending on the polymer concentrations, solution pH and degrees of substitution of Col-SH. The collagen component in the hybrid hydrogels retained its enzymatic degradability against collagenase, and the degradation time of the hydrogels increased with increasing polymer concentration. In vitro studies showed that bone marrow mesenchymal stem cells (BMSCs) exhibited rapid cell spreading and extensive cellular network formation on these hybrid hydrogels. In a rat infarction model, the infarcted left ventricle was injected with PBS, hybrid hydrogels, BMSCs or BMSC-encapsulating hybrid hydrogels. Echocardiography demonstrated that the hybrid hydrogels and BMSC-encapsulating hydrogels could increase the ejection fraction at 28 days compared to the PBS control group, resulting in improved cardiac function. Histology revealed that the injected hybrid hydrogels significantly reduced the infarct size and increased the wall thickness, and these were further improved with the BMSC-encapsulating hybrid hydrogel treatment, probably related to the enhanced engraftment and persistence of the BMSCs when delivered within the hybrid hydrogel. Thus, these injectable hybrid hydrogels combining intrinsic bioactivity of collagen, controlled mechanical properties and enhanced stability provide a versatile platform for functional cardiac regeneration.
authors.affiliation: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Xu
authors.affiliation: Cardiovascular Surgery Department, The First Affiliated Hospital of Soochow University, Suzhou 215012, People's Republic of China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China. Electronic address: cdeng@suda.edu.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.affiliation: Cardiovascular Surgery Department, The First Affiliated Hospital of Soochow University, Suzhou 215012, People's Republic of China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Teng
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Suuronen
authors.affiliation: Cardiovascular Surgery Department, The First Affiliated Hospital of Soochow University, Suzhou 215012, People's Republic of China. Electronic address: uuzyshen@aliyun.com.
authors.forename: Zhenya
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China. Electronic address: zyzhong@suda.edu.cn.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhong
mesh_terms: D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D055119:Elastic Modulus / Q000187:drug effects; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006334:Heart Function Tests; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007267:Injections; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects*; D012212:Rheology / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D034421:Sus scrofa; D014463:Ultrasonography
chemical_list: D000179:Acrylates; D001672:Biocompatible Materials; D020100:Hydrogels; D013438:Sulfhydryl Compounds; C000602669:oligo(acryloyl carbonate)-poly(ethylene glycol)-oligo(acryloyl carbonate) copolymer; D011092:Polyethylene Glycols; D003094:Collagen
keywords: Collagen; Hybrid hydrogels; Injectable hydrogels; Myocardial infarction; Stem cells