Decoupling Polymer Properties to Elucidate Mechanisms Governing Cell Behavior

Abstract

Determining how a biomaterial interacts with cells ("structure-function relationship") reflects its eventual clinical applicability. Therefore, a fundamental understanding of how individual material properties modulate cell-biomaterial interactions is pivotal to improving the efficacy and safety of clinically translatable biomaterial systems. However, due to the coupled nature of material properties, their individual effects on cellular responses are difficult to understand. Structure-function relationships can be more clearly understood by the effective decoupling of each individual parameter. In this article, we discuss three basic decoupling strategies: (1) surface modification, (2) cross-linking, and (3) combinatorial approaches (i.e., copolymerization and polymer blending). Relevant examples of coupled material properties are briefly reviewed in each section to highlight the need for improved decoupling methods. This follows with examples of more effective decoupling techniques, mainly from the perspective of three primary classes of synthetic materials: polyesters, polyethylene glycol, and polyacrylamide. Recent strides in decoupling methodologies, especially surface-patterning and combinatorial techniques, offer much promise in further understanding the structure-function relationships that largely govern the success of future advancements in biomaterials, tissue engineering, and drug delivery.

Pendant allyl crosslinking as a tunable shape memory actuator for vascular applications

“…Further tweaking of material properties and functions can be attained by altering other physicochemical properties such as molecular weight and gel content. Therefore, the new copolymerization format provides a unique, finely-tunable platform for studying structure-function relationships in order to better control biological responses and meet application requirements [47]. …”

Impact of secondary reactive species on the apparent decoupling of poly(ethylene glycol) diacrylate hydrogel average mesh size and modulus

“…32–34 Expanding the modulus range over which consistent average mesh size can be achieved would significantly advance the study of mechanobiology in 3D. 22 Similarly, expanding the mesh size range over which consistent mechanical properties can be achieved would advance the ability to design release vehicles for applications where specific hydrogel modulus or strength is required.…”

Poly(ε-Caprolactone)–Carbon Nanotube Composite Scaffolds for Enhanced Cardiac Differentiation of Human Mesenchymal Stem Cells

“…These characteristics include mechanical [1], chemical [2], electrical [3–5] and topographical [6] properties, and can be tailored to intricately control cell function and phenotype in order to enhance consequent therapeutic outcomes; in particular, from stem cell populations that possess the ability to differentiate into various cell types. By mimicking the microenvironmental cues that either stimulate cell type-specific differentiation of stem cells [7,8] or maintain physiological function of either progenitor or terminally differentiated cells [3,5], novel nanomaterial-based schemes can be developed to improve the efficacy of clinically translatable cell-based therapies.…”