Immunomodulation‐Based Strategy for Improving Soft Tissue and Metal Implant Integration and Its Implications in the Development of Metal Soft Tissue Materials

Abstract

The difficulties associated with metal implants and soft tissue integration have significantly affected the applications of metal implants in soft-tissue-related areas. Prompted by the close association between soft tissue integration and the immune response, an immunomodulation-based strategy is proposed to manipulate the immune microenvironment and improve metal implantsoft tissue integration. Considering their vital roles in soft tissue responses to metal implants, macrophages are used and the cytokines fingerprints of M1 and M2 macrophage immune microenvironments are evaluated for their potential modulatory effects on metal implant-soft tissue integration. The modulatory effects of different immune microenvironments on model soft tissue cells (human gingival epithelium cells) cultured on model metal implants (titanium alloy disks) are then described, with the underlying possible mechanism FAK-AKT-mTOR signaling unveiled. As further proof of concept, IL-4/PDA (polydopamine)-coated titanium alloy implants, aiming at modulating M2 macrophage polarization, are prepared and found to improve the in vivo metal implant-soft tissue integration. It is the authors' ambition that this immunomodulation-based strategy will change the negative perception and encourage the active development of metal materials with favorable soft tissue integration properties, thus improving the success rates of perforating metal implants and broadening their application in soft-tissue-related areas.

Tailoring Materials for Modulation of Macrophage Fate

“…During degradation, β-tricalcium phosphate substitutes could release Ca 2+ ions into local microenvironment to switch RAW 264.7 macrophages to M2 phenotype in vitro via activating the calcium-sensing receptor (CaSR) pathway, and significantly upregulate the expression of BMP-2 for enhancing osteogenesis. [222] Another in vitro work showed that the degradation particles from biphasic calcium phosphate www.advmat.de www.advancedsciencenews.com IL-4 -IL-4/polydopamine coating on Ti-based implants can boost M2 polarization and metal implant-soft tissue integration in vivo [189] ceramics could initiate the appropriate inflammatory response of RAW 264.7 macrophages at early phase to secrete signaling molecules that recruit MSCs and boost their osteogenic differentiation. [223] Nondegradable biomaterials, such as knitted polypropylene mesh, can frequently cause chronic foreign body reaction and fibrosis.…”

Biomimetic Lamellar Chitosan Scaffold for Soft Gingival Tissue Regeneration

“…As previously mentioned, macrophages and monocytes play the major role during a basic inflammatory response when a foreign material is implanted. [ 33 ] Cross‐linked collagen biomaterials have been shown to exhibit the highest resistance to enzymatic degradation, and natural collagen derived from human or animal resources may easily induce an increased production of pro‐inflammatory mediators in the macrophages and monocytes due to unwanted immune response. [ 34 ] This may explain the reason for the slow degradation and the higher inflammatory cell infiltration in the CM group.…”

Harnessing biomolecules for bioinspired dental biomaterials

“…), with or without cells, can exert strong control over the biological activity of biomolecules. 584,585 One rising approach to govern biological activity of dental biomaterials is the use of immunomodulatory systems, such as for dental implants 586 given the pivotal role the immune system plays in the response to materials. Strategies such as growth factor sequestration 587 are well-proven routes to take advantage of immunomodulation.…”