Strontium Functionalized in Biomaterials for Bone Tissue Engineering: A Prominent Role in Osteoimmunomodulation

Abstract

With the development of bone tissue engineering bio-scaffold materials by adding metallic ions to improve bone healing have been extensively explored in the past decades. Strontium a non-radioactive element, as an essential osteophilic trace element for the human body, has received widespread attention in the medical field due to its superior biological properties of inhibiting bone resorption and promoting osteogenesis. As the concept of osteoimmunology developed, the design of orthopedic biomaterials has gradually shifted from “immune-friendly” to “immunomodulatory” with the aim of promoting bone healing by modulating the immune microenvironment through implanted biomaterials. The process of bone healing can be regarded as an immune-induced procedure in which immune cells can target the effector cells such as macrophages, neutrophils, osteocytes, and osteoprogenitor cells through paracrine mechanisms, affecting pathological alveolar bone resorption and physiological bone regeneration. As a kind of crucial immune cell, macrophages play a critical role in the early period of wound repair and host defense after biomaterial implantation. Despite Sr-doped biomaterials being increasingly investigated, how extracellular Sr2+ guides the organism toward favorable osteogenesis by modulating macrophages in the bone tissue microenvironment has rarely been studied. This review focuses on recent knowledge that the trace element Sr regulates bone regeneration mechanisms through the regulation of macrophage polarization, which is significant for the future development of Sr-doped bone repair materials. We will also summarize the primary mechanism of Sr2+ in bone, including calcium-sensing receptor (CaSR) and osteogenesis-related signaling pathways.

Effect of strontium substitution on functional activity of phosphate-based glass

“…7A) Compared to BG, a high OPN expression with PSr6 in pre-osteoblast agreed with the ALP activity results, further validating the Sr-stimulated maturation of osteoblastic cells. 40,41 The biomineralization analysis through ARS assay micrographs show the increased distribution of stained mineralized regions in PSr6 (Fig. 7B).…”

Ion-incorporated titanium implants for staged regulation of antibacterial activity and immunoregulation-mediated osteogenesis

“…31,32 Strontium (Sr) is also a crucial trace element in the human body, mainly existing in bone tissue. 33,34 Due to its specific "dual effect" of promoting osteogenesis and inhibiting the osteoclast activity, Sr has been extensively used in biomaterial modification. 35 Besides, recent research reported that Sr could also promote M2 macrophage activation.…”

Zn–Sr-sintered true bone ceramics enhance bone repair and regeneration

“…Sr 2+ promotes the survival, proliferation, and differentiation of osteoblasts, but it could lead to the apoptosis of osteoclasts, thus reducing the rate of bone resorption. 23 In addition, Sr 2+ stimulates collagen and non-collagen synthesis. Continuously releasing Sr 2+ through a tissue interface implant is superior to oral administration because it continues to stimulate bone formation while minimizing the potential side effects associated with large oral doses of Sr 2+ .…”