Modulation of immune-inflammatory responses through surface modifications of biomaterials to promote bone healing and regeneration

Abstract

Control of inflammation is indispensable for optimal oral wound healing and tissue regeneration. Several biomaterials have been used to enhance the regenerative outcomes; however, the biomaterial implantation can ensure an immune-inflammatory response. The interface between the cells and the biomaterial surface plays a critical role in determining the success of soft and hard tissue regeneration. The initial inflammatory response upon biomaterial implantation helps in tissue repair and regeneration, however, persistant inflammation impairs the wound healing response. The cells interact with the biomaterials through extracellular matrix proteins leading to protein adsorption followed by recruitment, attachment, migration, and proliferation of several immune-inflammatory cells. Physical nanotopography of biomaterials, such as surface proteins, roughness, and porosity, is crucial for driving cellular attachment and migration. Similarly, modification of scaffold surface chemistry by adapting hydrophilicity, surface charge, surface coatings, can down-regulate the initiation of pro-inflammatory cascades. Besides, functionalization of scaffold surfaces with active biological molecules can down-regulate pro-inflammatory and pro-resorptive mediators' release as well as actively up-regulate anti-inflammatory markers. This review encompasses various strategies for the optimization of physical, chemical, and biological properties of biomaterial and the underlying mechanisms to modulate the immune-inflammatory response, thereby, promoting the tissue integration and subsequent soft and hard tissue regeneration potential of the administered biomaterial.

Keywords: Topography; implants; inflammation; oral disease; periodontitis; regeneration; scaffold.

Figure 1.

Local reactions to biomaterial surface by time. Phase I: surface wetting and adsorption of molecules (proteins) mainly derived from blood. Phase II: battle between local cells or bacteria for adhesion onto the surface. Phase III: formation of extracellular matrix (ECM) and focal adhesion contacts. Phase IV: the cells started to proliferate and differentiate hence tissue is re-modeled.

Figure 2.

The implantation of a biomedical implant triggers innate and adaptive host inflammatory responses. Periodontal pathogens in the biofilm activate a host immune response that leads to the production of several cytokines (represented by gray spheres) from oral epithelial cells and immune cells. Macrophages and neutrophils play an important role in the initial phase of inflammation, followed by the adaptive immune response orchestrated by lymphocytes.

Figure 3.

Schematic presentation of various surface coatings for dental implants and controlled-drug release systems for immune-inflammatory modulation.

Figure 4.

Physical, chemical, and biological modifications of biomaterials can dictate the cellular response to biomaterial scaffold implantation, thus, preventing foreign body giant cell formation. Such modifications can limit biofilm formation and can promote bacterial phagocytosis, opsonization, and apoptosis by macrophages. Optimization of surface properties of biomaterials can cause the macrophages to switch to the anti-inflammatory M2 phenotype.