No abstract

Biomaterials are one of efficient treatment options for tissue defects in regenerative medicine. Compared to synthetic materials which tend to induce chronic inflammatory response and fibrous capsule, extracellular matrix (ECM) scaffold materials composed of biopolymers are thought to be capable of inducing a pro-regenerative immune microenvironment and facilitate wound healing. Immune cells are the first line of response to implanted biomaterials. In particular, macrophages greatly affect cell behavior and the ultimate treatment outcome based on multiple cell phenotypes with various functions. The macrophage polarization status is considered as a general reflection of the characteristics of the immune microenvironment. Since numerous reports has emphasized the limitation of classical M1/M2 nomenclature, high-resolution techniques such as single-cell sequencing has been applied to recognize distinct macrophage phenotypes involved in host responses to biomaterials. After reviewing latest literatures that explored the immune microenvironment mediated by ECM scaffolds, this paper describe the behaviors of highly heterogeneous and plastic macrophages subpopulations which affect the tissue regeneration. The mechanisms by which ECM scaffolds interact with macrophages are also discussed from the perspectives of the ECM ultrastructure along with the nucleic acid, protein, and proteoglycan compositions, in order to provide targets for potential therapeutic modulation in regenerative medicine.

Fibrotic scar is one of the primary impediments to severe skin wound healing, characterized by excessive deposition of extracellular matrix (ECM) devoid of skin appendages including hair follicle (HF). Intriguingly, functional hair follicles can regenerate specifically in the large wound center of adult mice, termed wound-induced hair neogenesis (WIHN). Single-cell RNA sequencing (scRNA-Seq) comparisons of small and large wound showed increased activation of adaptive immune systems which might associated with predominance of papillary fibroblast (PF) in large wound. Integration the gene expression profiles of spatial transcriptomic (ST) and scRNA-Seq highlighted a pro-regenerative immune niche, composing of T cells, pro-inflammatory macrophage (PIM) and monocyte surrounding the migrating hair follicle stem cell (HFSC) and PF in large wound center. Local pro-regenerative immune response predicted by Cellchat provided potential therapeutic target for the further HF regeneration. Aligned electrospinning scaffolds were previously shown to accelerate small wound healing with the immunomodulatory effect of T cells and macrophages. Here we showed that wound recapitulated normal skin architecture with the implantation of scaffold despite wound size. Enlarged distribution of the pro-regenerative immune niche co-localization with PF may account for the well-proportioned de novo HF in scaffold-implanted group. Collectively, our study illustrated that manipulating the adaptive immune system may stimulate de novo HF regeneration via local cell-cell interactions.

This study calculates China’s provincial total factor productivity (TFP) and decomposition indexes. Then, a system of indicators is constructed to measure digitization, and an empirical analysis is conducted. The results show that (1) digitization can significantly improve TFP, especially technical efficiency, largely due to the increase in factor allocation efficiency and the quality of technological innovation resulting from digitization, a finding that remains valid even after a series of robustness tests. (2) The effect of digitization on the improvement of TFP is more pronounced in the central and western regions of China than in the east and more pronounced when economic development is in the service stage. The existence of a digital divide can diminish the positive effects of digitization. The regression results by industry show that digitization has a more significant positive impact on TFP in the secondary and tertiary industries than in the primary industries. (3) Further analysis shows that the process of digitization in raising TFP is nonlinear and that the positive effect of digitization on TFP is stronger when the level of industrial structure crosses the threshold. The findings of this paper bear some beneficial policy implications.

The usage of bone substitute granule materials has improved the clinical results of alveolar bone deficiencies treatment and thus broadened applications in implant dentistry. However, because of the complicated mechanisms controlling the foreign body response, no perfect solution can avoid the fibrotic encapsulation of materials till now, which may impair the results of bone regeneration, even cause the implant materials rejection. Recently, the concept of ‘osteoimmunology’ has been stressed. The outcomes of bone regeneration are proved to be related to the bio-physicochemical properties of biomaterials, which allow them to regulate the biological behaviours of both innate and adaptive immune cells. With the development of single cell transcriptome, the truly heterogeneity of osteo-immune cells has been clarifying, which is helpful to overcome the limitations of traditional M1/M2 macrophage nomenclature and drive the advancements of particulate biomaterials applications. This review aims at introducing the mechanisms of optimal osseointegration regulated by immune systems and provides feasible strategies for the design of next generation ‘osteoimmune-smart’ particulate bone substitute materials in dental clinic.