(A) Schematic of the scaffold fabrication; (B) image of an excised flap (10 mm scale bar) showing increased cell infiltration in the responsive scaffolds; and (C) quantification of cell infiltration based on scoring H+E stained sections after 7 or 14 days. Courtesy of Marjan Rafat and Debra T. Auguste.
(A) Schematic of the scaffold fabrication; (B) image of an excised flap (10 mm scale bar) showing increased cell infiltration in the responsive scaffolds; and (C) quantification of cell infiltration based on scoring H+E stained sections after 7 or 14 days. Courtesy of Marjan Rafat and Debra T. Auguste.

Stretchy scaffolds, which expand when local conditions change, could help promote cell regrowth, suggest researchers from Harvard University, City College of New York, Beth Israel Deaconess Medical Center, and Boston Children’s Hospital. The team, led by Debra T. Auguste, have designed a polymeric scaffold for treating skin and soft tissue wounds that swells in acidic conditions to allow more oxygen and nutrients reach growing cells [J.-O. You, et al., Biomaterials 57 (2015) 22-32, http://dx.doi.org/10.1016/j.biomaterials.2015.04.011].

Skin and soft tissue wounds arising from diabetic, pressure, and venous ulcers affect millions of patients every year. Treatment can include the use of skin scaffolds to provide a structural support on which recolonizing skin cells can stick, proliferate, and regrow. But fast growing cells like fibroblasts, which make up connective tissue, endothelial cells, that form the lining of blood vessels, and immune cells (or leukocytes), consume oxygen and nutrients very rapidly and, in the absence of a blood supply, can rapidly become paralyzed and die. This can make it difficult for such cells to survive in scaffolds long enough to promote healing.

So Auguste and her team have created porous scaffolds from dimethylaminoethyl methacrylate (DMAEMA), which swells in response to a decrease in pH, and a biocompatible polymer, 2-hydroxethyl methacrylate (HEMA), in different ratios. The team found that the pores of a 30/70 ratio DMAEMA/ HEMA scaffold nearly double in size when exposed to a pH of 6.5. This swelling, the researchers believe, enables more cells, oxygen, and nutrients to penetrate into the structure.

When implanted into rat models, the team found an increase in growth factors and cytokines, which are indicative of tissue regeneration, in the vicinity of the scaffold after 1-2 weeks and large amounts of granulation tissue, the new connective tissue and tiny blood vessels that form on wound surfaces during healing. There was also little or no sign of inflammation associated with the scaffold implants.

“pH-responsive scaffolds may prove useful in cell infiltration and cell survival because they stretch, which leads to improved oxygen transport and changes in cell gene expression that leads to vascularization, extracellular matrix production, and cytokine activation,” explains Auguste.

The stretchy DMAEMA/ HEMA scaffolds appear very promising for treating chronic wounds. The dynamically responsive scaffolds could have unique advantages, suggest the researchers.

“[These] scaffolds exhibit a self-actuating system that improves cell viability on time scales during which vascularization may be achieved,” Auguste told Materials Today.

The team is now working on degradable scaffolds that are suitable for clinical use.