Bio-inspired poly-DL-serine materials resist the foreign-body response

Donghui Zhang,Qi Chen,Jin Li,Minzhang Chen,Haodong Zhang,Chao Shi,Junyu Zhang,Jianglin Wan,Shengfu Chen,Zhongqian Qiao,Yufang Bi,Runhui Liu,Wenjing Zhang

doi:10.1038/s41467-021-25581-9

Abstract

Implantation-caused foreign-body response (FBR) is a commonly encountered issue and can result in failure of implants. The high L-serine content in low immunogenic silk sericin, and the high D-serine content as a neurotransmitter together inspire us to prepare poly-DL-serine (PSer) materials in mitigating the FBR. Here we report highly water soluble, biocompatible and easily accessible PSer hydrogels that cause negligible inflammatory response after subcutaneous implantation in mice for 1 week and 2 weeks. No obvious collagen capsulation is found surrounding the PSer hydrogels after 4 weeks, 3 months and 7 months post implantation. Histological analysis on inflammatory cytokines and RNA-seq assay both indicate that PSer hydrogels show low FBR, comparable to the Mock group. The anti-FBR performance of PSer hydrogels at all time points surpass the poly(ethyleneglycol) hydrogels that is widely utilized as bio-inert materials, implying the potent and wide application of PSer materials in implantable biomaterials and biomedical devices.

Highlights

Implantation-caused foreign-body response (FBR) is a commonly encountered issue and can result in failure of implants
Implantable biomaterials and devices will be recognized by the host immune system as foreign objects to initiate a series of interactions at the implant-host interface, which leads to the foreign-body response (FBR) including strong inflammatory responses, foreign-body giant cell formation, fibrosis, and eventually collagen encapsulation around the implants and isolation of implants from the host tissue[1,2,3,4,5,6,7,8,9,10,11,12]
Hydrogels of PSer and PEG were prepared by UVinitiated gelation of 20 wt% poly-DL-serine diacrylamide (PSerDA) and poly(ethyleneglycol) diacrylate (PEGDA) solutions, respectively, using Irgacure 2959 as the photoinitiator (Supplementary Table 2)

Summary

Introduction

Implantation-caused foreign-body response (FBR) is a commonly encountered issue and can result in failure of implants. Subcutaneous implantation in mice demonstrated that PSer hydrogels display superior anti-FBR properties than that of PEG hydrogels by showing low inflammatory response and low expression of related inflammatory cytokines and genes after implantation within the first 2 weeks, and no obvious collagen wrapping after implantation for at least 7 months (Fig. 1f).

Results

Conclusion