Biomimetic Tissue Engineering: Tuning the Immune and Inflammatory Response to Implantable Biomaterials

Abstract

Regenerative medicine technologies rely heavily on the use of well-designed biomaterials for therapeutic applications. The success of implantable biomaterials hinges upon the ability of the chosen biomaterial to negotiate with the biological barriers in vivo. The most significant of these barriers is the immune system, which is composed of a highly coordinated organization of cells that induce an inflammatory response to the implanted biomaterial. Biomimetic platforms have emerged as novel strategies that aim to use the principle of biomimicry as a means of immunomodulation. This principle has manifested itself in the form of biomimetic scaffolds that imitate the composition and structure of biological cells and tissues. Recent work in this area has demonstrated the promising potential these technologies hold in overcoming the barrier of the immune system and, thereby, improve their overall therapeutic efficacy. In this review, a broad overview of the use of these strategies across several diseases and future avenues of research utilizing these platforms is provided.

Extracellular Matrix‐Based Strategies for Immunomodulatory Biomaterials Engineering

“…Given the role of the ECM in structural support of tissues, there has been significant effort in developing ECM‐based scaffolds for tissue engineering and regenerative medicine . For these applications, a biomaterial scaffold is often used to encourage the adhesion and infiltration of cells, and their differentiation and organization into functional tissues.…”

“…These engineered tissues are designed with the ultimate goal of replacing damaged or diseased tissue. However, as with all materials implanted into the body, the immune response significantly influences the ability of engineered tissues to integrate and functionally interact with the host . The initial inflammatory response to implantation is dominated by activation of innate immune cells, including neutrophils and macrophages, followed by the later arrival of dendritic cells (DCs).…”

“…Thus, an emerging strategy in tissue engineering is to design materials that can directly control the host immune response . Furthermore, it has recently become appreciated that many ECM components in fact have natural immunomodulatory domains that bind to receptors found on immune cells, enabling their adhesion and regulating their function . Full length ECM proteins and/or ECM‐modeled peptides can be used in biomaterial scaffolds to mimic the natural regulatory role of the matrix on the immune system and generate desired immune cell functions to aid in the longevity and functionality of implants.…”

Current Advances in Immunomodulatory Biomaterials for Bone Regeneration

“…Recruited monocytes are then differentiated into macrophages in the presence of various proinflammatory cytokines produced by the other immune cells. These macrophages then adhere on the implanted materials, and the physicochemical properties of the materials play significant roles in macrophage plasticity, which influence the tissue healing process . It has been reported that the immune response to biomaterials may be attributed to the interactions between various proteins and the implanted biomaterials.…”

Freeze‐dry processing of three‐dimensional cell constructs for bone graft materials

“…Tissue engineering aims to fabricate biomimetic living tissues in vitro and in vivo and various biomaterials have been developed by tissue engineering technologies (Taraballi et al, ; Vedadghavami et al, ). Likewise, a number of cell‐based bone grafting materials have been developed using animal‐derived components (e.g., type I collagen) (Irawan, Sung, Higuchi, & Ikoma, ), biodegradable synthetic polymers (e.g., polylactic acid) (Gutierrez‐Sanchez, Escobar‐Barrios, Pozos‐Guillen, & Escobar‐Garcia, ), and ceramic materials (e.g., hydroxyapatite) (Przekora, ; Sun et al, ).…”