Methods for Implant Acceptance and Wound Healing: Material Selection and Implant Location Modulate Macrophage and Fibroblast Phenotypes

Abstract

This review focuses on materials and methods used to induce phenotypic changes in macrophages and fibroblasts. Herein, we give a brief overview on how changes in macrophages and fibroblasts phenotypes are critical biomarkers for identification of implant acceptance, wound healing effectiveness, and are also essential for evaluating the regenerative capabilities of some hybrid strategies that involve the combination of natural and synthetic materials. The different types of cells present during the host response have been extensively studied for evaluating the reaction to different materials and there are varied material approaches towards fabrication of biocompatible substrates. We discuss how natural and synthetic materials have been used to engineer desirable outcomes in lung, heart, liver, skin, and musculoskeletal implants, and how certain properties such as rigidity, surface shape, and porosity play key roles in the progression of the host response. Several fabrication strategies are discussed to control the phenotype of infiltrating macrophages and fibroblasts: decellularization of scaffolds, surface coatings, implant shape, and pore size apart from biochemical signaling pathways that can inhibit or accelerate unfavorable host responses. It is essential to factor all the different design principles and material fabrication criteria for evaluating the choice of implant materials or regenerative therapeutic strategies.

Time course study of long‐term biocompatibility and foreign body reaction to intraneural polyimide‐based implants

“…This dynamic in the capsule formation is coincident in time with the infiltration of macrophages in the nerve due to the implant described here which also peaked after 2 weeks and started to decrease thereafter (49) . It has been shown that macrophages and phagocytes are related with the nature of the material implanted and its degradation dynamics (50), (51) . Thus, biodegradable materials would stimulate a more M1 and phagocytic environment to eliminate the implant.…”

Modulation of Foreign Body Reaction against PDMS Implant by Grafting Topographically Different Poly(acrylic acid) Micropatterns

“…Many studies have focused on investigating the interaction between implanted biomaterials and the host response that causes capsular contracture via FBRs to improve the function and durability of PDMS‐based silicone implants . Although the mechanism of FBRs against PDMS implants has not yet been fully understood, it has been accepted that several cells including macrophages, fibroblasts, and myofibroblasts play a key role in encapsulating the implant with a dense collagenous avascular capsule . In particular, nonspecific protein adsorption and macrophage adhesion in the initial inflammatory process promote the overall FBRs.…”

“…[6][7][8] Although the mechanism of FBRs against PDMS implants has not yet been fully understood, it has been accepted that several cells including macrophages, fibroblasts, and myofibroblasts play a key role in encapsulating the implant with a dense collagenous avascular capsule. [9][10][11][12] In particular, nonspecific protein adsorption and macrophage adhesion in the initial inflammatory process promote the overall FBRs. Therefore, it has been considered important to suppress the FBRs by reducing the cell adhesion at the surface of the implant and controlling the cell behavior by modifying the characteristics of the implant such as surface chemistry and topography.…”

Minimizing Skin Scarring through Biomaterial Design

“…The importance of macrophages was initially documented in 1975 through a series of anti-serum and steroid suppression experiments where, unlike neutrophils, impaired or depleted macrophages had a negative impact on the time to wound healing. After these initial experiments, subsequent data confirmed these findings and it is now widely recognized that macrophages function as a critical regulatory cell in wound healing [37,45,46]. …”