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Functionalizable hydrogel microparticles of tunable size and stiffness for soft-tissue filler applications.

ABSTRACT: Particle size, stiffness and surface functionality are important in determining the injection site, safety and efficacy of injectable soft-tissue fillers. Methods to produce soft injectable biomaterials with controlled particle characteristics are therefore desirable. Here we report a method based on suspension photopolymerization and semi-interpenetrating network (semi-IPN) to synthesize soft, functionalizable, spherical hydrogel microparticles (MP) of independently tunable size and stiffness. MP were prepared using acrylated forms of polyethylene glycol (PEG), gelatin and hyaluronic acid. Semi-IPN MP of PEG-diacrylate and PEG were used to study the effect of process parameters on particle characteristics. The process parameters were systematically varied to produce MP with size ranging from 115 to 515?m and stiffness ranging from 190 to 1600Pa. In vitro studies showed that the MP thus prepared were cytocompatible. The ratio and identity of the polymers used to make the semi-IPN MP were varied to control their stiffness and to introduce amine groups for potential functionalization. Slow-release polymeric particles loaded with Rhodamine or dexamethasone were incorporated in the MP as a proof-of-principle of drug incorporation and release from the MP. This work has implications in preparing injectable biomaterials of natural or synthetic polymers for applications as soft-tissue fillers.

SUBMITTER: Chan KM

PROVIDER: S-EPMC4106431 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Functionalizable hydrogel microparticles of tunable size and stiffness for soft-tissue filler applications.

Chan Ka Man Carmen KM Li Randolph H RH Chapman Joseph W JW Trac Eric M EM Kobler James B JB Zeitels Steven M SM Langer Robert R Karajanagi Sandeep S SS

Acta biomaterialia 20140221 6

Particle size, stiffness and surface functionality are important in determining the injection site, safety and efficacy of injectable soft-tissue fillers. Methods to produce soft injectable biomaterials with controlled particle characteristics are therefore desirable. Here we report a method based on suspension photopolymerization and semi-interpenetrating network (semi-IPN) to synthesize soft, functionalizable, spherical hydrogel microparticles (MP) of independently tunable size and stiffness. ...[more]

PMID: 24561708

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Project description:Cultured meat has potential to diversify methods for protein production, but innovations in production efficiency will be required to make cultured meat a feasible protein alternative. Microcarriers provide a strategy to culture sufficient volumes of adherent cells in a bioreactor that are required for meat products. However, cell culture on inedible microcarriers involves extra downstream processing to dissociate cells prior to consumption. Here, we present edible microcarriers that can support the expansion and differentiation of myogenic cells in a single bioreactor system. To fabricate edible microcarriers with a scalable process, we used water-in-oil emulsions as templates for gelatin microparticles. We also developed a novel embossing technique to imprint edible microcarriers with grooved topology in order to test if microcarriers with striated surface texture can promote myoblast proliferation and differentiation in suspension culture. In this proof-of-concept demonstration, we showed that edible microcarriers with both smooth and grooved surface topologies supported the proliferation and differentiation of mouse myogenic C2C12 cells in a suspension culture. The grooved edible microcarriers showed a modest increase in the proliferation and alignment of myogenic cells compared to cells cultured on smooth, spherical microcarriers. During the expansion phase, we also observed the formation of cell-microcarrier aggregates or 'microtissues' for cells cultured on both smooth and grooved microcarriers. Myogenic microtissues cultured with smooth and grooved microcarriers showed similar characteristics in terms of myotube length, myotube volume fraction, and expression of myogenic markers. To establish feasibility of edible microcarriers for cultured meat, we showed that edible microcarriers supported the production of myogenic microtissue from C2C12 or bovine satellite muscle cells, which we harvested by centrifugation into a cookable meat patty that maintained its shape and exhibited browning during cooking. These findings demonstrate the potential of edible microcarriers for the scalable production of cultured meat in a single bioreactor.

Dataset Information

Functionalizable hydrogel microparticles of tunable size and stiffness for soft-tissue filler applications.

Publications

Functionalizable hydrogel microparticles of tunable size and stiffness for soft-tissue filler applications.

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