Single-cell RNA-seq reveals functionally distinct biomaterial degradation-related macrophage populations.

Macrophages play crucial roles in host tissue reaction to biomaterials upon implantation in vivo. However, the complexity of biomaterial degradation-related macrophage subpopulations that accumulate around the implanted biomaterials in situ is not fully understood. Here, using single cell RNA-seq, we analyze the transcriptome profiles of the various cell types around the scaffold to map the scaffold-induced reaction, in an unbiased approach. This enables mapping of all biomaterial degradation-associated cells at high resolution, revealing distinct subpopulations of tissue-resident macrophages as the major cellular sources of biomaterial degradation in situ. We also find that scaffold architecture can affect the mechanotransduction and catabolic activity of specific material degradation-related macrophage subpopulations in an Itgav-Mapk1-Stat3 dependent manner, eventually leading to differences in scaffold degradation rate in vivo. Our work dissects unanticipated aspects of the cellular and molecular basis of biomaterial degradation at the single-cell level, and provides a conceptual framework for developing functional tissue engineering scaffolds in future.

A collagen-coated sponge silk scaffold for functional meniscus regeneration.

Tissue engineering is a promising solution for meniscal regeneration after meniscectomy. However, in situ reconstruction still poses a formidable challenge due to multifunctional roles of the meniscus in the knee. In this study, we fabricate a silk sponge from 9% (w/v) silk fibroin solution through freeze drying and then coat its internal space and external surface with collagen sponge. Subsequently, various characteristics of the silk-collagen scaffold are evaluated, and cytocompatibility of the construct is assessed in vitro and subcutaneously. The efficacy of this composite scaffold for meniscal regeneration is evaluated through meniscus reconstruction in a rabbit meniscectomy model. It is found that the internally coated collagen sponge enhances the cytocompatibility of the silk sponge, and the external layer of collagen sponge significantly improves the initial frictional property. Additionally, the silk-collagen composite group shows more tissue ingrowth and less cartilage wear than the pure silk sponge group at 3 months postimplantation in situ. These findings thus demonstrate that the composite scaffold had less damage to the joint surface than the silk alone through promoting functional meniscal regeneration after meniscectomy, which indicates its clinical potential in meniscus reconstruction.