(38a) Soft Hydrogel Microparticles of Controlled Size and Stiffness with An Emulsion-Based Method

There is an increasing interest in developing methods to synthesize biomaterials with tunable micro/nanostructure, surface chemistries, and mechanical properties. Here we demonstrate a simple method to synthesize biocompatible hydrogel microparticles (MPs) with tunable size and mechanical properties that are also amenable to surface functionalization. Semi-interpenetrating networks of Polyethylene glycol (PEG)-diacrylate and PEG were prepared by photopolymerization in a water-in-oil emulsion to yield spherical PEG MPs. While the MPs were polydisperse in size, process parameters were systematically varied to prepare MPs with 90^th percentile size (D90) ranging from 48 µm to 900 µm.  The shear elastic modulus of the MPs was varied independent of MP-size by varying the relative amount of PEG-DA and PEG during synthesis. In addition, by replacing PEG with PEG bis(amine) during synthesis, amine groups were introduced in the MPs. The trinitrobenzene sulfonate assay confirmed that the amines introduced were accessible to functionalization with amine-reactive molecules. Dexamethasone (Dex) loaded-poly (DL-lactide-co-glycolide) microspheres (MS) were included in the emulsion during photopolymerization to prepare Dex-MS containing MPs that released Dex controllably over time. PEG MPs created with the emulsion photopolymerization method were biocompatible when evaluated in vitro using a cell proliferation assay and in vivo using implantation in guinea pigs. The method reported here can be used to prepare biocompatible, functionalizable hydrogel microparticles of tunable size and mechanical properties that may also be conjugated with controlled drug release particles to prepare smart materials with applications ranging from injectable biomaterials to tissue engineering to drug delivery.