Biologically Inspired, Cell‐Selective Release of Aptamer‐Trapped Growth Factors by Traction Forces

Abstract

Biomaterial scaffolds that are designed to incorporate dynamic, spatiotemporal information have the potential to interface with cells and tissues to direct behavior. Here, a bioinspired, programmable nanotechnology-based platform is described that harnesses cellular traction forces to activate growth factors, eliminating the need for exogenous triggers (e.g., light), spatially diffuse triggers (e.g., enzymes, pH changes), or passive activation (e.g., hydrolysis). Flexible aptamer technology is used to create modular, synthetic mimics of the Large Latent Complex that restrains transforming growth factor-β1 (TGF-β1). This flexible nanotechnology-based approach is shown here to work with both platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF-165), integrate with glass coverslips, polyacrylamide gels, and collagen scaffolds, enable activation by various cells (e.g., primary human dermal fibroblasts, HMEC-1 endothelial cells), and unlock fundamentally new capabilities such as selective activation of growth factors by differing cell types (e.g., activation by smooth muscle cells but not fibroblasts) within clinically relevant collagen sponges.

Hyaluronic Acid–Based Activatable Nanomaterials for Stimuli‐Responsive Imaging and Therapeutics: Beyond CD44‐Mediated Drug Delivery

“…Recently, the ability of nanomaterials to respond actively to local microenvironments, to enable spatial and temporal functions, has emerged as a promising strategy for diagnostic and therapeutic delivery . These nanocarriers can change their molecular structure, solubility, surface characteristics, shape, and self‐association or dissociation behaviors in response to endogenous stimuli such as pH changes, different levels of enzymes, cellular traction forces, reactive oxygen species (ROS), or glutathione in diseased tissues or in intracellular compartments. Also, they can respond to exogenous stimuli, such as laser irradiation or temperature changes, to generate an off/on activation of imaging or therapeutic function.…”

Angiogenesis in Tissue Engineering: As Nature Intended?

“…The release of molecules from the scaffold can be controlled by modifying the properties and composition of the material, TABLE 1 | List of common bioactive molecules used in tissue engineering vascularization and mentioned in this review. Lee et al, 2001;Gerhardt et al, 2003;Chiu and Radisic, 2010;Chow et al, 2010;Yuen et al, 2010;Shah et al, 2011;Zheng et al, 2012;Brudno et al, 2013;Nguyen et al, 2013;Alsop et al, 2014;Lai et al, 2014;Rich et al, 2014;Stamati et al, 2014;Wu et al, 2016;LaValley et al, 2017;Turner et al, 2017;Kuttappan et al, 2018;Stejskalová et al, 2019;Wang et al, 2019FGF Chow et al, 2010Tengood et al, 2011;Lai et al, 2014;Stamati et al, 2014;Kuttappan et al, 2018;Dong et al, 2019IGF Holland et al, 2005EGF Lai et al, 2014PDGF Tengood et al, 2011Brudno et al, 2013;Lai et al, 2014;Stejskalová et al, 2019;Wang et al, 2019Glycosaminoglycans Chow et al, 2010Chow et al, 2014;Wu et al, 2016 Frontiers in Bioengineering and Biotechnology | www.frontiersin.org as well as changing the method of retaining the drug (King and Krebsbach, 2012). Boontheekul et a...…”

“…A simple application of this consists of incorporating a drug into an alginate gel and allowing the cells to apply pressure on the matrix, stimulating molecule release (Lee et al, 2001). Stejskalová et al (2019) developed a method that uses cell-specific traction forces to trigger GF release from a biomaterial construct. The technology relies on the use of Traction Force-Activated Payloads (TrAP) composed by aptamers (short, single-stranded oligonucleotides that fold into 3D structures) flanked by a celladhesive peptide.…”

“…This method has been tested with VEGF on human microvascular endothelial cells (HMEC-1) and PDGF-BB on primary human dermal fibroblasts (HDFs), resulting in a remarkable increase in the proliferation rate for both cell types. Interestingly, TrAP allows the release of the payload in a temporal manner which is dependent on the expression of the cell surface receptor targeted by the adhesive peptide (Stejskalová et al, 2019).…”

Engineered full-length Fibronectin-based hydrogels sequester and present growth factors to promote regenerative responses in vitro and in vivo

“…Despite this, the potential of GFs has yet to be fully realised in translational medicine, partly due to their short half-life and rapid clearance in vivo 4,5 . Consequently, material-based strategies have been developed to control their sequestration and release, in order to reduce their required dosage and to control their local action [6][7][8] .…”