Preparation And Properties Of Enzyme-sensitive PEG Hydrogels

Over the past few years,tissue engineering has been developed rapidly for its huge potential in various biomedical applications,such as repairing or replacing the biological functions of the damaged or diseased tissue and so on.One of the key factors for successful tissue engineering is the selection of the scaffold material.Poly?ethylene glycol??PEG?is one of the most widely investigated building blocks used in hydrogels.PEG hydrogels are attractive potential tissue engineering scaffold materials because of their critical properties,such as good biocompatibility,non-immunogenity,and resistance to protein adsorption.In addition,the biodegradability of hydrogels can be conferred by the incorporation of degradable components,such as matrix metalloproteinase?MMP?degradable peptide?MMP?W?_X?.Polymeric oligomeric silsesquioxane?POSS?is a molecular hybrid nanocomposite material with molecular size between 1 and 3 nm.A number of POSS-based hybrid biomaterials exhibit enhanced thermal and mechanical stability arising from the inorganic properties and structural features of the POSS core.Moreover,these POSS-based hybrid materials have been widely used in the development of advanced biomaterials because of the critical properties of POSS nanoparticles,such as non-toxic,good biocompatibility.In this study,a series of enzyme-sensitive PEG hydrogels were prepared from 4-arm PEG-maleimide?4-arm-PEG-MAL?macromer crosslinked with MMP degradable peptide under physiological conditions by Michael-type addition polymerization in low concentration triethanolamine solution buffer?TEA,4mM?.Moreover,the infrared spectrogram,morpholopies,mechanical properties,swelling properties,degradation properties and in vitro cell compatibility of the hydrogels were characterized.The main content is divide d into the following two parts:1.A series of enzyme-sensitive poly?ethylene glycol??PEG?hydrogels with different polymer weight percentage and molecular weight of PEG were successfully prepared via Michael-type addition between 4-arm-PEG-MAL and MMP degradable peptide.The morpholopies,mechanical properties,swelling properties,degradation properties were studied.SEM images confirmed a porous structure and the pore size increased with the increase of the PEG chain length.Rheological measurements indicated that all the hydrogels exhibited the characteristics of elastomer and the cross-linking density had a correlation to the content of MMP degradable peptide and 4-arm-PEG-MAL.PEG hydrogels exhibited a good water absorption capacity.Biological activities of the PEG₂₀-7.5%hydrogels were evaluated by in vitro enzymatic degradation and in vitro cell compatibility on mesenchymal stem cells?MSCs?and the results showed that the hydrogel was biocompatible and the hydrogels could be degraded by exogenously delivered MMPs or cell-secreted MMPs.2.Based on the previous study of PEG hydrogels,a specific polymer weight percentage?7.5%?of PEG hydrogels was chosen to be used in later study.Although PEG₂₀-7.5%was in accordance with the requirements of tissue engineering scaffold,its mechanical strength was still insufficient.In order to improve the mechanical properties of the hydrogel material,the POSS nanoparticles were suspended in the long chain of the PEG polymer to modify and harden the hard segment to.The POSS-PEG prepolymer was prepared via Michael-type addition between 4-arm-PEG-MAL and POSS-SH in tetrahydrofuran to improve the solubility and dispersity of POSS nanoparticles in aqueous solution.Thus,a series of inorganic-organic POSS-PEG hybrid hydrogels with different molecular weight of PEG and POSS loading level were prepared by covalently grafting POSS into PEG and further cross-linking by MMP degradable peptide via Michael-type addition polymerization.The microstructure,mechanical properties,swelling properties and enzymatic degradation were compared between POSS-PEG hybrid hydrogel and pure PEG hydrogel.To the best of our knowledge,this is the first time for POSS-containing hybrid hydrogels to be prepared in water,indicating that it is an excellent material suitable for 3D cell culture.In vitro cell viability study on human umbilical vein endothelial cells?HUVEC?for 3D cell culture indicates POSS-PEG hydrogels is non-toxic and have good compatibility.In conclusion,a series of enzyme-sensitive hydrogels with different polymer weight percentage,molecular weight of PEG and POSS loading level were successfully prepared via Michael-type addition,providing theoretical and practical guidance for the the preparation of hydrogels materials with different porosity,mechanical properties,swelling properties,degradation properties and biological activity.