Transient cellular adhesion on poly(ethylene-glycol)-dimethacrylate hydrogels facilitates a novel stem cell bandage approach

• Published in: PloS one 2018-08, Vol.13 (8), p.e0202825-e0202825
• Main Authors: Asawa, Rosita R, Belkowski, Jessica C, Schmitt, Daniel A, Hernandez, Elizabeth M, Babcock, Ann E, Lochner, Christina K, Baca, Holly N, Rylatt, Colleen M, Steffes, Isaac S, VanSteenburg, Jace J, Diaz, Karina E, Doroski, Derek M
• Format: Article
• Language: English
• Subjects: Adhesion; Adhesives; Arginine; Arginine - chemistry; Aspartic acid; Aspartic Acid - chemistry; Biocompatibility; Biology; Biology and Life Sciences; Biomedical materials; Cell Adhesion; Cell Culture Techniques - methods; Cell Differentiation; Cell growth; Cells, Cultured; Engineering and Technology; Glycine; Glycine - chemistry; Growth factors; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate; Hydrogels; Laboratories; Medical research; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchyme; Organic chemistry; Peptides; Physical Sciences; Polyethylene glycol; Polymers; Research and Analysis Methods; Stem cells; Stromal cells; Tissue engineering; Tissue Engineering - methods
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0202825

We discovered a transient adhesion property in poly(ethylene glycol) dimethacrylate (PEG-DMA) hydrogels and employed it to develop a novel "stem cell bandage" model of cellular delivery. First, we cultured human mesenchymal stromal cells (MSCs) on the surface of PEG-DMA hydrogels with high amounts of arginine-glycine-aspartic acid (RGD) adhesive peptides (RGD++) or without RGD (RGD-). On day 1, MSCs underwent an initial adhesion to RGD- hydrogels that was not significantly different over 13 days (n = 6). In addition, cells appeared to be well spread by day 3. Significantly fewer cells were present on RGD- hydrogels on day 15 compared to day 9, suggesting that RGD- hydrogels allow for an initial cellular adhesion that is stable for multiple days, but transient over longer periods with a decrease by day 15. This initial adhesion is especially surprising considering that PEG-DMA does not contain any biological adhesion motifs and is almost chemically identical to poly(ethylene glycol) diacrylate (PEG-DA), which has been shown to be non-adhesive without RGD. We hypothesized that MSCs could be cultured on RGD- PEG-DMA hydrogels and then applied to a wound site to deliver cells in a novel approach that we refer to as a "stem cell bandage". RGD- donor hydrogels were successfully able to deliver MSCs to PEG-DMA acceptor hydrogels with high RGD content (RGD++) or low amounts of RGD (RGD+). Our novel "bandage" approach promoted cell delivery to these model surfaces while preventing cells from diffusing away. This stem cell delivery strategy may provide advantages over more common stem cell delivery approaches such as direct injections or encapsulation and thus may be valuable as an alternative tissue engineering approach.