Long-term local PDGF delivery using porous microspheres modified with heparin for tendon healing of rotator cuff tendinitis in a rabbit model

In this study, we prepared the platelet-derived growth factor-containing porous microspheres modified with heparin (PDGF/Hep-PMSs) and investigated their anti-inflammatory and tendon healing effects on rotator cuff (RC) tendinitis rabbit model. PDGF/Hep-PMSs suppressed the mRNA levels of six pro-inflammatory cytokines (i.e., MMP-3, MMP-13, COX-2, ADAMTS-5, IL-6, and TNF-alpha) in inflamed tenocytes. Long-term local delivery of PDGF/Hep-PMSs into tendon tissues of RC tendinitis decreased the mRNA levels of six pro-inflammatory cytokines and increased the mRNA levels of anti-inflammatory cytokines including IL-4, IL-10, and IL-13. Antiinflammatory effects of PDGF/Hep-PMSs might have contributed to enhance the collagen content, tenogenic markers, stiffness, and tensile strength of tendons, eventually leading to tendon restoration. Our findings suggest that the long-term local PDGF delivery of PDGF/Hep-PMSs have a great potential to enhance tendon healing of RC tendinitis by suppressing inflammation responses.