The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity

Abstract

Bone, cartilage, and soft tissue regeneration is a complex spatiotemporal process recruiting a variety of cell types, whose activity and interplay must be precisely mediated for effective healing post-injury. Although extensive strides have been made in the understanding of the immune microenvironment processes governing bone, cartilage, and soft tissue regeneration, effective clinical translation of these mechanisms remains a challenge. Regulation of the immune microenvironment is increasingly becoming a favorable target for bone, cartilage, and soft tissue regeneration; therefore, an in-depth understanding of the communication between immune cells and functional tissue cells would be valuable. Herein, we review the regulatory role of the immune microenvironment in the promotion and maintenance of stem cell states in the context of bone, cartilage, and soft tissue repair and regeneration. We discuss the roles of various immune cell subsets in bone, cartilage, and soft tissue repair and regeneration processes and introduce novel strategies, for example, biomaterial-targeting of immune cell activity, aimed at regulating healing. Understanding the mechanisms of the crosstalk between the immune microenvironment and regeneration pathways may shed light on new therapeutic opportunities for enhancing bone, cartilage, and soft tissue regeneration through regulation of the immune microenvironment.

Elimination of methicillin-resistant Staphylococcus aureus biofilms on titanium implants via photothermally-triggered nitric oxide and immunotherapy for enhanced osseointegration

“…These pro-inflammatory cytokines augment the activity of osteoclasts and decrease the recruitment or migration of MSCs. This results in bone disconnection and poor osseointegration [ 68 – 72 ]. In this study, Ti-PDA@SNP-OGP significantly down-regulated the mRNA expression levels of M1 markers CD86, iNOS, and CD11C and up-regulated the mRNA expression levels of M2 markers CD206, Arg-1, and CD163.…”

“…The crosstalk between MSCs and RAW264.7 cells plays a vital role in the improvement of implant osseointegration [ 72 – 74 ]. Therefore, the osteogenic induction effect of RAW264.7 cells on MSCs upon the stimulation of Ti-PDA@SNP-OGP should be carefully considered.…”

Recent development in multizonal scaffolds for osteochondral regeneration

“…There are four continuous and overlapping stages involving with the regeneration of both the bone and the cartilage tissues, including hemostasis, inflammation, repair, and remodeling ( Fig. 7 A) [ 324 ]. Tissue engineering strategies with the use of MZSs for OC regeneration mainly play direct roles in the latter two stages.…”

“…Adapted with permission from Ref. [ 324 ]. B. Anatomical illustration of major types of cells residing in osteochondral tissue.…”

A bibliometric analysis of hotpots and trends for the relationship between skin inflammation and regeneration

“…Since then, researchers have discovered that immune cells not only eliminate microbial and cellular debris but also promote tissue growth and wound repair (12,13). Furthermore, increasing research has revealed the crucial role of immune cells in healing as well as the underlying regulatory mechanism (14,15). In other clinical studies, immunocompromised individuals have been reported to exhibit impaired wound repair, which also indicates the important role of immune cells in skin healing (16)(17)(18).…”