Enzymatic co-crosslinking of star-shaped poly(ethylene glycol)tyramine and hyaluronic acid tyramine conjugates provides elastic biocompatible and biodegradable hydrogels  

作　　者：Rong Wang Xiaobin Huang Bram Zoetebier Pieter JDijkstra Marcel Karperien 

机构地区：[1]Department of Developmental BioEngineering,Faculty of Science and Technology,Tech Med Centre,University of Twente,P.O.Box 217,7500 AE,Enschede,the Netherlands [2]Radboudumc,Dept.of Dentistry-Regenerative Biomaterials,Radboud University Medical Center,Philips van Leydenlaan 25,6525 EX Nijmegen,The Netherlands [3]Department of Oral and Maxillofacial Surgery,School of Dental Medicine,University of Pennsylvania,240 South 40th Street,Philadelphia,PA 19104-6030,US

出　　处：《Bioactive Materials》2023年第2期53-63,共11页生物活性材料（英文）

基　　金：support by a grant from the Dutch government to the Netherlands Institute for Regenerative Medicine(NIRM,Grant No.FES0908);support of the Netherlands Organisation for Scientific Research(NWO)P15-23(Project 1)“Activating resident stem cells”and EFRO OPOost 00867 Orthros TR.

摘　　要：A combination of the viscoelastic properties of hyaluronic acid(HA)and the elastic properties of star shaped 8-arm poly(ethylene glycol)(8-arm PEG)was used to design in-situ forming hydrogels.Hydrogels were prepared by the enzymatic crosslinking of a partially tyramine modified 8-arm PEG and a tyramine conjugated HA using horseradish peroxidase in the presence of hydrogen peroxide.Hydrogels of the homopolymer conjugates and mixtures thereof were rapidly formed within seconds under physiological conditions at low polymer and enzyme concentrations.Elastic hydrogels with high gel content(≥95%)and high storage moduli(up to 22.4 kPa)were obtained.An in vitro study in the presence of hyaluronidase(100 U/mL)revealed that with increasing PEG content the degradation time of the hybrid hydrogels increased up to several weeks,whereas hydrogels composed of only hyaluronic acid degraded within 2 weeks.Human mesenchymal stem cells(hMSCs)incorporated in the hybrid hydrogels remained viable as shown by a PrestoBlue and a live-dead assay,confirming the biocompatibility of the constructs.The production of an extracellular matrix by re-differentiation of encapsulated human chondrocytes was followed over a period of 28 days.Gene expression indicated that these highly elastic hydrogels induced an enhanced production of collagen type II.At low PEG-TA/HA-TA ratios a higher expression of SOX 9 and ACAN was observed.These results indicate that by modulating the ratio of PEG/HA,injectable hydrogels can be prepared applicable as scaffolds for tissue regeneration applications.

关 键 词：PEG-OH8 HA Enzymatic crosslinking hydrogel Degradation Proliferation&differentiation 

分 类 号：TQ427.26[化学工程]