Successful osseointegration requires the production of a mechanically competent collagenous matrix, by osteoblasts, at the implant site. Lysophosphatidic acid (LPA) is a bioactive lipid which we discovered interacts with vitamin D3 (D3) to secure human osteoblast (hOB) maturation on both titanium (Ti) and hydroxyapatite.

We therefore covalently attached LPA and a related compound, (3S) 1-fluoro-3-hydroxy-4-butyl-1-phosphate (FHBP), to both solid and porous Ti discs and seeded them with hOBs to assess their ability to support D3-induced cell maturation. Solid functionalised discs were washed and reused a further two times, whilst other discs were stored for 6 months.

Increased alkaline phosphatase (ALP) activity indicated that both LPA and FHBP-modified Ti serve as superior substrates for securing D3-induced hOB maturation compared to unmodified metal (p < 0.001). Although total ALP activity was less for cells on recycled discs and after storage, enzyme levels were still significantly greater compared to hOBs grown on control Ti. LPA and D3 co-treatment also resulted in an increase in osteocalcin (∼17ng/ml versus 6ng/ml for D3 alone, P < 0.001) and collagen synthesis (∼310pg/ml versus <10pg/ml for D3 alone, P < 0.001).

Research is ongoing to evaluate the efficacy of our modified Ti surfaces to secure hOB formation from their stem cell progenitors.