Alginate/gelatin/boron-doped hydroxyapatite-coated Ti implants: in vitro and in vivo evaluation of osseointegration

PAZARÇEVİREN A. E., EVİS Z., Dikmen T., Altunbaş K., Yaprakçı M. V., KESKİN D., ...More

Bio-Design and Manufacturing, 2023 (Scopus) identifier

  • Publication Type: Article / Article
  • Publication Date: 2023
  • Doi Number: 10.1007/s42242-022-00218-y
  • Journal Name: Bio-Design and Manufacturing
  • Journal Indexes: Scopus
  • Keywords: Alginate/gelatin, Boron, Implant coating, Osteochondral model, Titanium
  • Middle East Technical University Affiliated: Yes


© 2023, Zhejiang University Press.In this study, boron-doped hydroxyapatite (BHT)-loaded alginate/gelatin-based (A/G) hydrogel coating on Ti was fabricated to support bone integration through triggering osteoinduction, vascularization and immunomodulation. Initially, highly reproducible, cheap and time-effective BHT was produced, which significantly promoted higher osteogenic and angiogenic maturation, while a mild innate immune response was observed. The immense potential of BHT was evidenced by the production of a gap-filling A/G/BHT interphase on Ti implants to mimic the osseous extracellular matrix to achieve functional bridging and exert control over the course of innate immune response. We initially aminosilanized the implant surface using 3-aminopropyl triethoxysilane, and then coated it with 0.25% w/v alginate with 20 mM 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide to allow the A/G/BHT pre-gel to disperse evenly and covalently attach on the surface. The pre-gel was added with 0.2 M NaCl to homogeneously blend BHT in the structure without inducing ionic crosslinking. Then, the coated implants were freeze-dried and stored. The coated layer demonstrated high cohesive and adhesive strength, and 8-month-long shelf-life at room temperature and normal humidity. The A/G/BHT was able to coat an irregularly shaped Ti implant. Osteoblasts and endothelial cells thrived on the A/G/BHT, and it demonstrated greatly improved osteogenic and angiogenic capacity. Moreover, A/G/BHT maintained macrophage viability and generated an acute increase in immune response that could be resolved rapidly. Finally, A/G/BHT was shown to induce the robust integration of implant in a rabbit femur osteochondral model within 2 months. Therefore, we concluded that A/G/BHT coatings could serve as a multifunctional reservoir, promoting the strong and rapid osseointegration of metallic implants. Graphic abstract: [Figure not available: see fulltext.]