Surface modification of electrospun fibers with mechano-growth factor for mitigating the foreign-body reaction

Abstract

The implantation of synthetic polymeric scaffolds induced foreign-body reaction (FBR) seriously influence the wound healing and impair functionality recovery. A novel short peptide, mechano-growth factor (MGF), was introduced in this study to modify an electrospun polycaprolactone (PCL) fibrous scaffold to direct the macrophage phenotype transition and mitigate the FBR. In vitro studies discovered the cell signal transduction mechanism of MGF regulates the macrophage polarization via the expression of related genes and proteins. We found that macrophages response the MGF stimuli via endocytosis, then MGF promotes the histone acetylation and upregulates the STAT6 expression to direct an anti-inflammatory phenotype transition. Subsequently, an immunoregulatory electrospun PCL fibrous scaffold was modified by silk fibroin (SF) single-component layer-by-layer assembly, and the SF was decorated with MGF via click chemistry. Macrophages seeded on scaffold to identify the function of MGF modified scaffold in directing macrophage polarization in vitro . Parallelly, rat subcutaneous implantation model and rat tendon adhesion model were performed to detect the immunomodulatory ability of the MGF-modified scaffold in vivo . The results demonstrate that MGF-modified scaffold is beneficial to the transformation of macrophages to M2 phenotype in vitro . More importantly, MGF-functionalized scaffold can inhibit the FBR at the subcutaneous tissue and prevent tissue adhesion.

Advanced strategies to thwart foreign body response to implantable devices

“…The implant promoted graft patency with a minimal fibrous tissue formation in Lewis rats and bare PCL scaffold post-28-day implantation in rats. 234 Poly-L-lactic acid (PLLA), with a low biodegradation rate and mild immune response, has been clinically used as an implantable material.…”

“…In another study, Song et al functionalized the LBL silk fibroin (SF) modified PCL nanofibrous scaffolds with mechano growth factor‐1 (MGF‐1), an alternative splicing product of insulin growth factor‐1. Through the upregulation of the anti‐inflammatory signaling cascade such as signal transducer and activator of transcription 6 activation, MGF‐1/SF/PCL scaffolds induce thinner fibrotic tissue formation and higher M2/M1 ratio than the SF/PCL and bare PCL scaffold post‐28‐day implantation in rats 234 …”

“…Through the upregulation of the anti‐inflammatory signaling cascade such as signal transducer and activator of transcription 6 activation, MGF‐1/SF/PCL scaffolds induce thinner fibrotic tissue formation and higher M2/M1 ratio than the SF/PCL and bare PCL scaffold post‐28‐day implantation in rats. 234 …”

Improving hard metal implant and soft tissue integration by modulating the “inflammatory-fibrous complex” response

“…After soft tissue interventions, metal materials inevitably trigger inflammatory and subsequent fibrotic reactions [ 11 , 12 ]. Uncontrolled inflammation can cause function defects, loosening, and failure of the implants [ [13] , [14] , [15] ].…”

Osteoimmune reaction caused by a novel silicocarnotite bioceramic promoting osteogenesis through the MAPK pathway

“…2; the macrophage shape of the CPS group presented a visibly elongated shape when compared with that in HA, indicating an anti-inflammatory phenotype in CPS. Studies have found that a micropatterned substrate can promote cell elongation and prime these cells into the M2 phenotype compared with a flat substrate, 24 while in atherosclerosis, M2 cells exhibited an elongated morphology. 25 Moreover, it has been found that cell elongation always appears with the promotion of M2-inducing cytokines and inhibition of M1-inducing cytokines, 26 consistent with our results as shown in Fig.…”