Bio Focus: Taking heart in gelatin for tissue engineering

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he use of animals for drug testing remains a critical component of biomedical progress. However, materials advances might eventually render such tests obsolete. Apart from complex bioethical issues, animal testing suffers from a number of major scientific drawbacks, including slow experimental cycle times and species-dependent response variations; for example, observations in mice do not necessarily predict corresponding effects in humans. As an exciting alternative to animal models, Kit Parker and colleagues at Harvard University envision one day growing small-scale samples of relevant human tissues for high-throughput drug response assays, bypassing the need for live animals. Specifically, Parker’s team has focused on culturing cardiac muscle cells toward the development of “Heart on a Chip” technologies. A few years ago, the team demonstrated biocomposite materials dubbed “muscular thin films” (MTFs) that were comprised of cardiac muscle tissue grown in thin layers on the surfaces

of silicone polymer (polydimethylsiloxane, PDMS); the polymer could then be pushed and pulled by voltageinduced cellular muscle contractions. In a contribution in the July issue of Biomaterials (DOI: 10.1016/j.biomaterials.2014.03.052; p. 5462), Parker’s team demonstrated improved MTF platforms that support healthier heart tissues than previously possible and which permit mechanical probing of important tissue qualities. The key advance involves the exploration of gelatin hydrogels as new substrates for cardiac tissue growth. Gelatin’s advantages over previously used scaffold materials stem from its softness and its surface chemistry. Gelatin’s low elastic modulus more closely mimics that of a living heart (10–15 kPa) in comparison to PDMS (which is stiffer). Furthermore, gelatin is mainly composed of collagen, the major constituent of the heart’s extracellular matrix. Heart cells thus readily adhere to gelatin in vitro without the need for surface treatment, as required for both PDMS and alginate substrates. The researchers used micropatterning techniques to grow cardiac muscle tissue on the surfaces of gelatin cantilevers.

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(a) Fabrication of gelatin muscular thin films; (b) Optical micrographs of voltage-paced muscular thin film cantilevers in which the muscle tissue is either in a relaxed ("diastole") or contracted ("systole") state. Reproduced with permission from Biomaterials 35 (2014) DOI: 10.1016/j. biomaterials.2014.03.052; p. 5462. © 2014 Elsevier Ltd.

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During gelatin hydrogel casting, a PDMS stamp was used to produce arrays of linear trenches, 10 μm × 10 μm in cross section, patterned in relief into the gel’s top surface. Such trenches promote anisotropic myocardial growth into aligned structures that mimic native heart tissue. Cantilevers with these micropatterned surfaces are then carved by laser etching through the gel thickness, with cuts made into gelatin regions that are only weakly bound to a supporting glass substrate; the cantilevers are