AVS 62nd International Symposium & Exhibition | |
Biomaterial Interfaces | Tuesday Sessions |
Session BI-TuA |
Session: | Cells and Microorganisms at Surfaces |
Presenter: | Adam Celiz, Harvard University |
Authors: | A. Celiz, Harvard University J. Smith, University of Nottingham, UK A. Patel, Massachusetts Institute of Technology R. Langer, Massachusetts Institute of Technology D. Anderson, Massachusetts Institute of Technology D. Mooney, Harvard University L. Young, University of Nottingham, UK M. Davies, University of Nottingham, UK C. Denning, University of Nottingham, UK M.R. Alexander, University of Nottingham, UK |
Correspondent: | Click to Email |
A key hurdle in translating stem cell therapies from research to industrial scale and clinical application is to produce the necessary numbers of cells in xeno-free, defined culture systems. For example, a heart attack can cause a loss of 1 billion cardiomyocytes and similar cell numbers are lost during progression of other conditions such as multiple sclerosis and diabetes. To meet the demand for such high cell numbers, materials scientists have been challenged to discover new synthetic biomaterials as xeno-free growth substrates.1 We apply a high throughput materials discovery approach to identify a novel polymer for hPSC culture using microarray screening of an unprecedented chemical space (141 monomers, polymerized alone and mixed to form 909 unique polymers, tested in 4356 individual assays). This identified the first synthetic polymeric substrate that achieves both pluripotent hPSC expansion (in the commercially available defined culture media, StemPro and mTeSR1) and subsequent multi-lineage differentiation into representatives of the three germ layers, namely cardiomyocytes, hepatocyte-like cells and neural progenitors.2 Surface analysis techniques such as ToF-SIMS and XPS were used to identify chemical moieties at the biomaterial interface that contributed to maintaining hPSC pluripotency. The identification of these controlling surface moieties was essential in the development of a facile scale up procedure from arrayed spots to coated cultureware that can be used off-the-shelf.
An alternative strategy for cell and tissue regeneration is to harness the natural regenerative capacity of the human body through activation of quiescent cell populations. Biomaterials such as hydrogels that mimic native extracellular matrix can be synthesized and implanted in vivo to present biophysical and biochemical cues to their surroundings and activate/traffic these cell populations towards a desired therapeutic effect.3 Novel bioactive hydrogels, synthesized through bioorthogonal click chemistry methods, will be presented that can activate and regulate quiescent cell populations to aid regeneration of lost tissue after trauma or injury. The utility of these new materials will be demonstrated through muscle regeneration in a hind limb ischemia mouse model.
1. A. D. Celiz et al. Nat. Mater. (2014) 13, 570.
2. A. D. Celiz et al. Adv. Mater. in press adma.201501351R1.
3. C. A. Cezar et al. Adv. Drug Deliv. Rev. (2014) http://dx.doi.org/10.1016/j.addr.2014.09.008.