Journal
RESEARCH
Volume 2022, Issue -, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.34133/2022/9823784
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Funding
- National Natural Science Foundation of China [32222041, 82072425, 82072498, 21875092]
- Natural Science Foundation of Jiangsu Province [BK20220059, BE2020666]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) [LCZX202003]
- Special Project of Diag-nosis and Treatment Technology for Key Clinical Diseases in Suzhou [LCZX202003]
- Jiangsu Specially Appointed Professor Program
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX22_3217]
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This study reports a one-step biomimetic surface strategy to improve the integration of osteoimplants and bone in osteoporotic patients by introducing BMSC recruiting and osteoinductive abilities onto metallic osteoimplants. The use of a bioadhesive molecular peptide mimic inspired by mussel foot proteins enables the functionalization of implant surfaces with BMSC-targeting and osteogenic growth peptides. The rational dual functionalization significantly improves implant biocompatibility and facilitates the recruitment, proliferation, and differentiation of endogenous BMSCs, leading to enhanced interfacial osteogenesis and osteointegration.
For patients with osteoporosis, the therapeutic outcomes of osteoimplants are substantially affected by the impaired proliferation, migration, and osteogenic differentiation abilities of bone marrow mesenchymal stem cells (BMSCs). To improve bone-implant integration in osteoporotic condition, here we reported a one-step biomimetic surface strategy to introduce BMSC recruiting and osteoinductive abilities onto metallic osteoimplants. In our design, the bioadhesive molecular peptide mimic inspired by mussel foot proteins (Mfps) was used as molecular bridging for surface functionalization. Specifically, a BMSC-targeting peptide sequence (E7) and an osteogenic growth peptide (Y5) were grafted onto the titanium implant surfaces through a mussel adhesion mechanism. We found that a rational E7/Y5 feeding ratio could lead to an optimal dual functionalization capable of not only significantly improving the biocompatibility of the implant but also enabling it to recruit endogenous BMSCs for colonization, proliferation, and osteogenic differentiation. Mechanistically, the E7-assisted in situ recruitment of endogenous BMSCs as well as the enhanced interfacial osteogenesis and osteointegration was associated with activation of the C-X-C chemokine receptor type 4 (CXCR4) receptor on the cell surface and promotion of stromal cell-derived factor (SDF-1 alpha) autocrine secretion. We anticipated that rational dual-functional surfaces through bioadhesive molecular mimics will provide a simple, effective, nonimmunogenic, and safe means to improve the clinical outcomes of intraosseous implants, especially under osteoporotic conditions.
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