Tissue Engineering Tools For Modulation of the Immune Response

Abstract

Tissue engineering scaffolds have emerged as a powerful tool within regenerative medicine. These materials are being designed to create environments that promote regeneration through a combination of: (i) scaffold architecture, (ii) the use of scaffolds as vehicles for transplanting progenitor cells, and/or (iii) localized delivery of inductive factors or genes encoding for these inductive factors. This review describes the techniques associated with each of these components. Additionally, the immune response is increasingly recognized as a factor influencing regeneration. The immune reaction to an implant begins with an acute response to the injury and innate recognition of foreign materials, with the subsequent chronic immune response involving specific recognition of antigens (e.g., transplanted cells) by the adaptive immune response, which can eventually lead to rejection of the implant. Thus, we also describe the impact of each component on the immune response, and strategies (e.g., material design, anti-inflammatory cytokine delivery, and immune cell recruitment/transplantation) to modulate, yet not eliminate, the local immune response in order to promote regeneration, which represents another important tool for regenerative medicine.

In vitro hemocompatibility and cytocompatibility of a three-layered vascular scaffold fabricated by sequential electrospinning of PCL, collagen, and PLLA nanofibers

“…32 Several strategies have been developed to modulate the inflammatory response toward regeneration rather than repair by changing the surface wettability, creating micro/nano structures, and fabricating aligned fibers. 31 Jenney et al and Young et al found that macrophage adhesion decreases with increasing hydrophobicity. 33,34 In contrast, Brodbeck et al demonstrated that macrophage adhesion is decreased on hydrophilic and anionic surfaces.…”

Materials that harness and modulate the immune system

“…Biomaterial surface chemistry, surface topography, and microscale architecture are all general approaches that have been applied to reduce immune reactions to implanted materials by limiting protein deposition, which controls immune cell interaction and activation. 6 Examples of these approaches are summarized in Table I. However, where physicochemical methods have reached their limit of benefit, research efforts to design biomaterials that modulate pro-inflammatory immune responses associated with implantation of biomaterials have intensified.…”

“…These properties can influence protein deposition, provisional matrix formation (temporary extracellular matrix that is remodeled over time), immune cell attachment, and ultimately host immune responses. 6 Studies such as those by Acharya et al suggest that surface immobilization of naturally derived bio-ligands is an approach with potential to modulate inflammatory responses to biomaterial implants. 14 Hume et al adopted an approach of this category, functionalizing polyethylene glycol (PEG) hydrogels with covalently immobilized immunosuppressive biological agents—transforming growth factor 1 (TGF-β1) and interleukin-10 (IL-10)—to reduce inflammatory responses to cell-laden material carriers.…”

A hypothesis-driven parametric study of effects of polymeric scaffold properties on tissue engineered neovessel formation

“…[11,15]). For the purposes herein, we first reduced this extensive list of parameters to a focused list consisting of those scaffold parameters that have been most frequently investigated experimentally (Table 1).…”