High-throughput synthesis, analysis, and optimization of injectable hydrogels for protein delivery.

High-throughput synthesis, analysis, and optimization of injectable hydrogels for protein delivery. Biomacromolecules. 2019 Nov 05;: Authors: Xu F, Corbett B, Bell S, Zhang C, Budi Hartono M, Farsangi ZJ, MacGregor JF, Hoare T Abstract The development of in situ-gelling hydrogels that can enable prolonged protein release is increasingly important due to the emergence of a growing number of protein-based therapeutics. Herein, we describe a high-throughput strategy to fabricate, characterize, and subsequently optimize hydrazone-crosslinked in situ-gelling hydrogels for protein delivery. Hydrogels are fabricated using an automated high-throughput robot to mix a variety of thermoresponsive, non-thermoresponsive, charged, neutral, naturally-sourced, and synthetic polymers functionalized with hydrazide or aldehyde groups, generating in situ-gelling hydrogels with well-defined compositions within a 96-well plate. High-throughput characterization strategies are subsequently developed to enable on-plate analysis of hydrogel swelling, mechanics, degradation, transparency, and protein (ovalbumin) release kinetics that yield results consistent with those collected using traditional bulk hydrogel analysis techniques. Dynamic regression and latent variable modeling are then applied to fit performance statistics to the collected data set; subsequently, numerical optimization is used to identify mixtures of precursor polymers that exhibit targeted c...
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research