Modulating Macrophage Phenotype by Sustained MicroRNA Delivery Improves Host‐Implant Integration

Abstract

Biomedical implant failure due to the host's response remains a challenging problem. In particular, the formation of the fibrous capsule is a common barrier for the normal function of implants. Currently, there is mounting evidence indicating that the polarization state of macrophages plays an important role in effecting the foreign body reaction (FBR). This opens up a potential avenue for improving host‐implant integration. Here, electrospun poly(caprolactone‐co‐ethyl ethylene phosphate) nanofiber scaffolds are utilized to deliver microRNAs (miRs) to induce macrophage polarization and modulate FBR. Specifically, C57BL/6 mice that are treated with M2‐inducing miRs, Let‐7c and miR‐124, display relatively thinner fibrous capsule formation around the scaffolds at both Week 2 and 4, as compared to treatment with M1‐inducing miR, Anti‐Let‐7c. Histological analysis shows that the density of blood vessels in the scaffolds are the highest in miR‐124 treatment group, followed by Anti‐Let‐7c and Let‐7c treatment groups. Based on immunohistochemical quantifications, these miR‐encapsulated nanofiber scaffolds are useful for localized and sustained delivery of functional miRs and are able to modulate macrophage polarization during the first 2 weeks of implantation to result in significant alteration in host‐implant integration at longer time points.

Cutting Edge Endogenous Promoting and Exogenous Driven Strategies for Bone Regeneration

“…Due to the fact that miRNAs possess an intrinsic ability to target multiple genes and pathways, miRNA therapeutics (enhancement of the expression of miRNA with RNA mimics or miRNA expression inhibition by antagomiRs) is being considered as a coming realistic therapeutic strategy to elicit a more pronounced bone regeneration in bone-related pathologies. Since macrophages orchestrate a critical role in mediating host body reaction toward implanted biomaterial, the possibility of adding miRNAs therapeutics to pro-osteogenic scaffolds is being explored to induce M2 macrophage polarization [ 136 ].…”

Implantable PEKK/tantalum microparticles composite with improved surface performances for regulating cell behaviors, promoting bone formation and osseointegration

“…PAEK is a non-degradable and bioinert polymer, therefore, the formation of fibrous tissue encapsulation around the PAEK implant and the weak osteointegration performance has been reported in previous studies [ 15 ]. The layer of fibrous tissues developed between bioinert implants and host bone tissue may be long-term unstable, which may eventually result in the loosening and failure of implants [ 16 ]. Many investigations have been carried to improve the bioactivity of PEEK for promoting bone formation and osteointegration, and these strategies include surface modification with either physical/chemical ways, and composites with bioactive fillers were applied [ 17 , 18 ].…”

The Role of Epigenetic Functionalization of Implants and Biomaterials in Osseointegration and Bone Regeneration—A Review

“…In order to investigate the use of miRNA as a means to regulate foreign body reaction towards implants, electrospun poly(caprolactone- co -ethyl ethylene phosphate) (PCLEEP) fiber scaffold containing miRNAs has been developed [ 107 ]. The PCLEEP polymer was suggested to have an enhanced biodegradability compared to PCL.…”

“…The PCLEEP polymer was suggested to have an enhanced biodegradability compared to PCL. MiRNA-124 and let-7, targeting macrophages and regulating macrophage polarization towards a M2 macrophage phenotype, were used [ 107 ]. A sustained release of miRNAs for at least 30 days was reported and the results showed that a scaffold containing Let-7 and miRNA-124 was able to induce a M2 macrophage polarization as well as a thinner fibrous capsule around the scaffold [ 107 ].…”

“…MiRNA-124 and let-7, targeting macrophages and regulating macrophage polarization towards a M2 macrophage phenotype, were used [ 107 ]. A sustained release of miRNAs for at least 30 days was reported and the results showed that a scaffold containing Let-7 and miRNA-124 was able to induce a M2 macrophage polarization as well as a thinner fibrous capsule around the scaffold [ 107 ]. As a consequence of insertion of an implant specimen, e.g., prosthetics, a foreign body response process starts leading to the formation of a collagenous capsule around the implant specimen.…”