Abstract
Regenerative medicine is aimed at restoring normal tissue function and can benefit from the application of tissue engineering and nano-therapeutics. In order for regenerative therapies to be effective, the spatiotemporal integration of tissue-engineered scaffolds by the native tissue, and the binding/release of therapeutic payloads by nano-materials, must be tightly controlled at the nanoscale in order to direct cell fate. However, due to a lack of insight regarding cell–material interactions at the nanoscale and subsequent downstream signaling, the clinical translation of regenerative therapies is limited due to poor material integration, rapid clearance, and complications such as graft-versus-host disease. This review paper is intended to outline our current understanding of cell–material interactions with the aim of highlighting potential areas for knowledge advancement or application in the field of regenerative medicine. This is achieved by reviewing the nanoscale organization of key cell surface receptors, the current techniques used to control the presentation of cell-interactive molecules on material surfaces, and the most advanced techniques for characterizing the interactions that occur between cell surface receptors and materials intended for use in regenerative medicine.Lay SummaryThe combination of biology, chemistry, materials science, and imaging technology affords exciting opportunities to better diagnose and treat a wide range of diseases. Recent advances in imaging technologies have enabled better understanding of the specific interactions that occur between human cells and their immediate surroundings in both health and disease. This biological understanding can be used to design smart therapies and tissue replacements that better mimic native tissue. Here, we discuss the advances in molecular biology and technologies that can be employed to functionalize materials and characterize their interaction with biological entities to facilitate the design of more sophisticated medical therapies.
Highlights
The goal of regenerative medicine is to restore normal tissue function by combining molecular biology and material science [1]
Such biomaterials range in scale from tissueengineered scaffolds intended for whole organ replacement to nano-materials intended for targeted therapeutic drug delivery
We focus on integrins and cadherins (Fig. 1), and how they provide important targets in regenerative medicine to ensure that the interactions between implanted biomaterials and the surrounding cells lead to effective regenerative outcomes
Summary
The goal of regenerative medicine is to restore normal tissue function by combining molecular biology and material science [1]. In order to understand the relationship between receptor density and the adhesive forces of cadherins, one study used self-assembled monolayers of thiols, to which they bound extracellular fragments of E-cadherin, and measured cell binding using single-molecule force spectroscopy (SMFS) [56] They found that a lateral distance of 5–11 nm was optimal for E-cadherin function. Tension sensors enable the study of the downstream signaling that is associated with force generation following receptor binding All of these techniques enable the study of the nanoscale receptor spatial organization and the downstream effects on cell fate when interfaced with a biomaterial demonstrate that osteoblasts and fibroblasts are unable to stably adhere to hydrogel surfaces when the distance between neighboring adhesion ligands is > 70 nm in one direction even if the ligand spacing between neighboring ligands in the opposite direction is ≤ 70 nm [86]. By varying both the surface density and spatial distribution of RGD on the surface of poly(ethylene oxide)-based hydrogel, it has been shown that fibroblast migration speed is a function of surface ligand density and that clustering ligands reduces the ligand density required to support cell migration [88]
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