ZnO quantum dots-embedded collagen/polyanion composite hydrogels with integrated functions of degradation tracking/inhibition and gene delivery

Abstract

A collagen/poly(2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt) (collagen/PNaAMPS) interpenetrating polymer network (IPN) hydrogel was prepared by simultaneous reaction of EDC/NHS-mediated crosslinking of concentrated collagen solution and poly(ethylene glycol) diacrylate crosslinking NaAMPS in a sealed syringe. The collagen/PNaAMPS hydrogels were freeze-dried and immersed in an aqueous solution of PDMAEMA-capped ZnO quantum dots (QDs) to construct a ZnO QDs-laden collagen/PNaAMPS IPN hydrogel. The composite hydrogel containing nearly 90% water exhibited light transmission from 85% to 96%. Introducing the PNaAMPS network considerably improved the mechanical strength of the pristine collagen gel, whereas loading ZnO QDs only slightly affected the optical properties, mechanical properties and water absorption. Strikingly, the loaded ZnO QDs were found to serve dual roles – tracking the degradation of collagen by observing directly the reduction of fluorescence intensity in hydrogels; and as a collagenase inhibitor by the proposed interaction with metalloenzyme, an important characteristic which could be used to prolong the degradation time of pure collagen without physical screening of the IPN network. We also demonstrated that anionic PNaAMPS was able to dampen the cytotoxicity of composite hydrogels by neutralizing positive charges of ZnO QDs. The composite hydrogels carrying rabbit corneal anterior stromal fibroblasts and PolyJet™/DNA complexes could achieve the efficient expression of luciferase and EGFP genes. The model composite hydrogels offer an approach to design a novel corneal substitute with integrated functions of real-time degradation tracking, degradation inhibition and gene delivery for the specific treatment of ophthalmic diseases.