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Review
. 2011 Oct 30;155(2):193-9.
doi: 10.1016/j.jconrel.2011.04.007. Epub 2011 Apr 14.

Hyaluronic acid-based clinical biomaterials derived for cell and molecule delivery in regenerative medicine

Glenn D Prestwich  1
Affiliations
Review

Hyaluronic acid-based clinical biomaterials derived for cell and molecule delivery in regenerative medicine

Glenn D Prestwich. J Control Release. .

Abstract

The development of injectable and biocompatible vehicles for delivery, retention, growth, and differentiation of stem cells is of paramount importance for regenerative medicine. For cell therapy and the development of clinical combination products, we created a hyaluronan (HA)-based synthetic extracellular matrix (sECM) that provides highly reproducible, manufacturable, approvable, and affordable biomaterials. The composition of the sECM can be customized for use with progenitor and mature cell populations obtained from skin, fat, liver, heart, muscle, bone, cartilage, nerves, and other tissues. This overview describes the design criteria for "living" HA derivatives, and the many uses of this in situ crosslinkable HA-based sECM hydrogel for three-dimensional (3-D) culture of cells in vitro and translational use in vivo. Recent advances allow rapid expansion and recovery of cells in 3-D, and the bioprinting of engineered tissue constructs. The uses of HA-derived sECMs for cell and molecule delivery in vivo will be reviewed, including applications in cancer biology and tumor imaging.

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Figures

Figure 1
Figure 1
Sample chemical substructures of monolithic (top) and living (bottom) chemical modifications of hyaluronic acid.
Figure 2
Figure 2
Formation of the crosslinked synthetic ECM Extracel from thiol-modified HA, thiol-modified gelatin, and poly(ethylene glycol) diacrylate.
Figure 3
Figure 3
Culture of the canine kidney MDCK cell line in HyStem-C, supplemented with 100 μg/mL mouse laminin, leads to formation of acinar structures. Key: green, Alexa 488 phalloidin for actin; blue, Draq-5 for cell nuclei. Image courtesy of Glycosan Biosystems, Y. Qui, R. McCall, V. Mironov, X. Wen.
Figure 4
Figure 4
Scanning electron micrograph of human hepatocytes encapsulated in Extracel and cultured for 5 days. Image obtained by G. Yang and provided by Glycosan Biosystems.
Figure 5
Figure 5
Subcutaneous injection of Endgenitor human endothelial colony forming cells (ECFCs) with human adipose-derived stem cells and a cocktail of growth factors in Extracel-HP after 1 week. An anastomosed human vasculature (red-stained endothelium by anti-human CD31 and brown nuclei stained with anti-human nuclear matrix protein) is visible in the presence of rat cells (blue) and rat blood (uncolored in red-lined blood vessels). Image courtesy of Glycosan Biosystems and R. I. Grove (Endgenitor).
Figure 6
Figure 6
Injection of MiaPaCa-2 cells labeled with red fluorescent protein as an Extracel suspension into the pancreas of a nude mouse. After 4 weeks, the tumor mass is visible as a large orange mass (lower center); individual metastases are visible as red foci in the intestinal folds and elsewhere in the abdomen. Image courtesy of Jill Shea.
See this image and copyright information in PMC

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