Promoting musculoskeletal system soft tissue regeneration by biomaterial-mediated modulation of macrophage polarization

Abstract

Musculoskeletal disorders are common in clinical practice. Repairing critical-sized defects in musculoskeletal systems remains a challenge for researchers and surgeons, requiring the application of tissue engineering biomaterials. Successful application depends on the response of the host tissue to the biomaterial and specific healing process of each anatomical structure. The commonly-held view is that biomaterials should be biocompatible to minimize local host immune response. However, a growing number of studies have shown that active modulation of the immune cells, particularly macrophages, via biomaterials is an effective way to control immune response and promote tissue regeneration as well as biomaterial integration. Therefore, we critically review the role of macrophages in the repair of injured musculoskeletal system soft tissues, which have relatively poor regenerative capacities, as well as discuss further enhancement of target tissue regeneration via modulation of macrophage polarization by biomaterial-mediated immunomodulation (biomaterial properties and delivery systems). This active regulation approach rather than passive-evade strategy maximizes the potential of biomaterials to promote musculoskeletal system soft tissue regeneration and provides alternative therapeutic options for repairing critical-sized defects.

What is the clinically significant ideal mesenchymal stromal cell count in the management of osteoarthritis of the knee? – Meta-analysis of randomized controlled trials

“…When a complement molecule binds to MSC, it induces phagocytosis by macrophages and in turn, M2 polarization occurs to establish a tolerogenic environment. 47 With the rapid clearance of MSCs from the systemic circulation, a therapeutic response being observed was due to the interplay between complement and monocytephagocyte system. 48 MSCs attenuates autophagy and promote cellular survival, proliferation, differentiation, and restore the functional tissues in the degenerative environment.…”

Preparation and Antimicrobial Activity of Chitosan and Its Derivatives: A Concise Review

“…has become a critical issue in medical practice. The tissue regeneration process is complex, with a number of growth factors, DNA, RNA, being involved in mediating cellular response and modulating cellular behavior [ 101 ]. Wound healing can be compromised or delayed by many local and systemic factors, leading to the need for specialized treatment [ 102 ].…”

Immunomodulatory Actions of Mesenchymal Stromal Cells (MSCs) in Osteoarthritis of the Knee

“…Complement systems exhibit an interplay between MSCs to influence the biological features of engrafted cells. When a complement molecule binds to MSC, it induces phagocytosis by macrophages and in turn, M2 polarization occurs to establish a tolerogenic environment [43]. With the rapid clearance of MSCs from the systemic circulation, a therapeutic response being observed was due to the interplay between complement and monocyte-phagocyte system [44].…”

“…The most responsible cellular component for the immunogenic environment in knee joint is synovial macrophage (Mϕ) [43]. Once MSCs are administered, proinflammatory macrophages (M1Mϕ) are activated by IFN-γ and TNF-α polarise to anti-inflammatory macrophages (M2Mϕ) which releases soluble factors and downregulate inflammatory and apoptotic events in cartilage which in turn upregulate the chondrogenic regeneration and remodeling [47][48][49].…”