Covalently tethered transforming growth factor beta in PEG hydrogels promotes chondrogenic differentiation of encapsulated human mesenchymal stem cells

Methods to precisely control growth factor presentation in a local and sustained fashion are of increasing interest for a number of complex tissue engineering applications. The cytokine transforming growth factor beta (TGF beta) plays a key role in promoting the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). Traditional chondrogenic approaches utilize soluble delivery, an approach with limited application for clinical translation. In this work, we introduce a reactive thiol onto TGF beta and covalently tether the growth factor into poly(ethylene glycol) (PEG) hydrogels using a photoinitiated thiol- acrylate polymerization mechanism. We demonstrate the bioactivity of thiolated TGF beta, before and after polymerization, using a SMAD2 reporter cell line. hMSCs were encapsulated in PEG hydrogelswith and without tethered TGF beta, and subsequently assayed for glycosaminoglycan and collagen II production as indicators of chondrogenesis. Over a 21-day time course, tethered TGF beta promoted chondrogenesis at levels similar to a positive control using solubly dosed growth factor. These results provide evidence that tethered TGF beta materials can be successfully used to promote chondrogenic differentiation of MSCs.