Tuning the biomimetic behavior of scaffolds for regenerative medicine through surface modifications

Abstract

Tissue engineering and regenerative medicine rely extensively on biomaterial scaffolds to support cell adhesion, proliferation, and differentiation physically and chemically in vitro and in vivo. Changes to the surface characteristics of the scaffolds have the greatest impact on cell response. Here, we discuss five dominant surface modification approaches used to biomimetically improve the most common scaffolds for tissue engineering, those based on aliphatic polyesters. Scaffolds of aliphatic polyesters such as poly(l-lactic acid), poly(l-lactic-co-glycolic acid), and poly(ε-caprolactone) are often used in tissue engineering because they provide desirable, tunable properties such as ease of manufacturing, good mechanical properties, and nontoxic degradation products. However, cell-surface interactions necessary for tissue engineering are limited on these materials by their smooth postfabrication surfaces, hydrophobicity, and lack of recognizable biochemical binding sites. The surface modification techniques that have been developed for synthetic polymer scaffolds reduce initial barriers to cell adhesion, proliferation, and differentiation. Topographical modification, protein adsorption, mineral coating, functional group incorporation, and biomacromolecule immobilization each contribute through varying mechanisms to improving cell interactions with aliphatic polyester scaffolds. Furthermore, rational combination of methods from these categories can provide nuanced, specific environments for targeted tissue development.

Keywords: RGD; biomaterial; cell response; functionalization; nanofibers; protein adsorption; simulated body fluid; topography.

FIGURE 1

Repeating unit chemical structure of three aliphatic polyester polymers commonly used for tissue engineering scaffolds. These polymers are highly hydrophobic and provide limited functional group availability for chemical reactivity with cells

FIGURE 2

Tissue engineering scaffold surface modification techniques. Mineral deposition subsection represents hydroxyapatite

FIGURE 3

Varying approaches in topographical modifications for guiding cell response. Figures adapted from Dalby et al. (2007), S. J. Kim, Jang, Park, and Min (2010), W. J. Li, Laurencin, Caterson, Tuan, and Ko (2002), Miller, Thapa, Haberstroh, and Webster (2004), Thanki et al. (2006), and Unadkat et al. (2011), with permission from Elsevier, Springer Nature, and Wiley

FIGURE 4

Scanning electron micrographs relate simulated body fluid (SBF) ion concentration to surface topography. Scale bar = 10 μm. Inset scale bar = 1 μm. The deposited mineral composition remains similar, suggesting the solution concentration primarily affects structure, with ratio-dependent transitions from spherulitic to plate-like to net-like. Importantly, cell adhesion rates were highest on the spherulitic structure. Previous publications in SBF coating techniques increased ion concentrations to accelerate precipitation without addressing effects on surface morphology. Reproduced from (Choi & Murphy, 2012) with permission from The Royal Society of Chemistry

FIGURE 5

Potential hydrogel-derived responsive surface modifications