Composite boron doped hydroxyapatite-tricalcium phosphate/alginate/gelatin hydrogel coating on titanium implants: Osseointegration and immunomodulation study

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2022-7-25
Pazarçeviren, Ahmet Engin
A successful bridging and osseointegration of Ti-6Al-4V implant (Ti) at the defect site are strongly dependent on the effectiveness of the interphase. Achieving such a robust interface could diminish micromovements, shearing on the defected bone and loosening over time. Here, a boron doped hydroxyapatite (A/G/BHT) loaded alginate/gelatin-based (A/G) hydrogel coating on Ti was produced to support bone integration through prompting osteoinduction, vascularization and immunomodulation. Initially, highly reproducible, cheap and time-effective BHT was produced and it significantly promoted higher osteogenic and angiogenic maturation while a mild innate immune response was obtained. Proving the bone tissue engineering (BTE) potential of BHT, a gap-filling A/G/BHT layer was fabricated on Ti to mimic bone extracellular matrix to establish biofunctional bridge. Ti surface was aminosilanized the implant surface by 3-Aminopropyl ethoxysilane (APTES), then coated implant surface with 0.25% w/v alginate with 20 mM 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) to allow A/G/BHT pre-gel to disperse homogeneously and covalently attach on the surface. The pre-gel was added 0.2 M sodium chloride (NaCl) to blend BHT in the structure without inducing ionic crosslinking. Then, coated implants were freeze-dried. The interphase layer demonstrated high cohesive and adhesive strength (A/G/BHT as 2.66 N compared to A/G 1.72 N), 8 month-long shelf-life at room temperature and normal humidity. Osteoblasts and endothelial cells thrived on A/G/BHT, which allowed improved osteogenic and angiogenic activity. Moreover, A/G/BHT generated an acute increase in immune response that could be resolved rapidly. Finally, A/G/BHT was shown to induce robust integration of the implant in rabbit femur osteochondral model within 2 months.

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Citation Formats
A. E. Pazarçeviren, “Composite boron doped hydroxyapatite-tricalcium phosphate/alginate/gelatin hydrogel coating on titanium implants: Osseointegration and immunomodulation study,” Ph.D. - Doctoral Program, Middle East Technical University, 2022.