Strontium-Doped Hydroxyapatite Coating Improves Osteo/Angiogenesis for Ameliorative Graft-Bone Integration via the Macrophage-Derived Cytokines-Mediated Integrin Signal Pathway.

Abstract

Polyethylene terephthalate (PET) artificial ligaments, renowned for their superior mechanical properties, have been extensively adopted in anterior cruciate ligament (ACL) reconstruction surgeries. However, the inherent bio-inertness of PET introduces formidable barriers to graft-bone integration, a critical aspect of rehabilitation. Previous interventions, ranging from surface roughening to chemical modifications, have aimed to address this challenge; however, consistently effective techniques for inducing graft-bone integration remain scarce. Our study employed advanced surface-coating methodologies to introduce strontium-doped hydroxyapatite (SrHA) onto PET ligaments. Detailed scanning electron microscopy (SEM) examinations revealed a uniform and integrative coating of SrHA on PET fibers. Furthermore, spectroscopic analysis confirmed the steady release of strontium ions from the coated surface under physiological conditions. In-depth cellular studies proved that extracellular strontium emanating from SrHA-coated PET (PET@SrHA) ligaments actively steers the M2 macrophage polarization. Additionally, macrophages (Mφs) manifested a heightened secretion of prohealing cytokines when exposed to PET@SrHA. Subsequent investigations showed that these cytokines acted as mediators, activating integrin signaling pathways among macrophages, vascular endothelial cells, and osteoblasts. As a direct consequence, an increased rate of angiogenesis and osteogenic differentiation was observed, vital for graft-bone integration following ACL reconstruction with PET@SrHA ligaments. From a biochemical standpoint, our results pinpoint strontium ions as influential immunomodulators, sculpting the graft-bone interface's immune environment. This insight presents the SrHA-coating technique as a viable therapeutic strategy, holding sound promise for improving angiogenesis and osseointegration outcomes during ACL reconstruction using PET-based grafts.