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

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Abstract

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.

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Acknowledgements

Authors would like to thank Center of Excellence in Biomaterials and Tissue Engineering (BIOMATEN) for the support provided. Authors also acknowledge financial support provided by National Boron Institute (BOREN, Grant No: 2018-31-07-25-001).

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Authors and Affiliations

  1. Department of Engineering Sciences, Middle East Technical University, Ankara, Turkey

    Ahmet E. Pazarçeviren, Zafer Evis, Dilek Keskin & Ayşen Tezcaner

  2. Department of Histology and Embryology, Afyon Kocatepe University, Afyon, Turkey

    Tayfun Dikmen & Korhan Altunbaş

  3. Department of Surgery, Afyon Kocatepe University, Afyon, Turkey

    Mustafa V. Yaprakçı

  4. Center of Excellence in Biomaterials and Tissue Engineering, Ankara, Turkey

    Dilek Keskin & Ayşen Tezcaner

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  1. Ahmet E. Pazarçeviren
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  2. Zafer Evis
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  4. Korhan Altunbaş
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  5. Mustafa V. Yaprakçı
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  6. Dilek Keskin
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  7. Ayşen Tezcaner
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Contributions

Conceptualization: AEP, KA, ZE and AT; methodology: AEP, TD and MVY; data analysis: AEP and TD; writing—original draft preparation: AEP; writing—review and editing: DK, ZE and AT; ZE provided sources; KA, ZE and AT performed supervision. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Ayşen Tezcaner.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All animal procedures in our study were approved by the Institutional Animal Care and Use Committee of Afyon Kocatepe University (Date: 18.09.2018, Decision No.: 49533702/147).

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Pazarçeviren, A.E., Evis, Z., Dikmen, T. et al. Alginate/gelatin/boron-doped hydroxyapatite-coated Ti implants: in vitro and in vivo evaluation of osseointegration. Bio-des. Manuf. 6, 217–242 (2023). https://doi.org/10.1007/s42242-022-00218-y

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