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Bio-Design and Manufacturing  2023 Vol.6 No.3 P.217-242

http://doi.org/10.1007/s42242-022-00218-y


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


Author(s):  Ahmet E. Pazarçeviren, Zafer Evis, Tayfun Dikmen, Korhan Altunbaş, Mustafa V. Yaprakçı, Dilek Keskin & Ayşen Tezcaner

Affiliation(s):  Department of Engineering Sciences, Middle East Technical University, Ankara, Turkey; more

Corresponding email(s):   tezcaner@metu.edu.tr

Key Words:  Boron, Alginate/gelatin, Implant coating, Titanium, Osteochondral model


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Ahmet E. Pazarçeviren, Zafer Evis, Tayfun Dikmen, Korhan Altunbaş, Mustafa V. Yaprakçı, Dilek Keskin & Ayşen Tezcaner. Alginate/gelatin/boron-doped hydroxyapatite-coated Ti implants: in vitro and in vivo evaluation of osseointegration[J]. Journal of Zhejiang University Science D, 2023, 6(3): 217-242.

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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.

中东技术大学Ayşen Tezcaner等 | 海藻酸盐明胶硼掺杂羟基磷灰石涂层钛植入物骨融合的体外和体内评估

本研究论文在钛上制造了硼掺杂羟基磷灰石(BHT)负载的海藻酸/明胶基(A/G)水凝胶涂层,通过触发骨诱导、血管化和免疫调节支持骨融合。首先,研究人员制造了可重复性高的、易获取的和有时效性的BHT,它明显地促进了更高的成骨和血管生成成熟,同时仅观察到轻微的先天免疫反应。BHT的巨大潜力可通过在钛植入物上产生填充间隙的A/G/BHT间相来证明,通过模拟骨质细胞外基质来实现功能桥接并对先天免疫反应的过程进行控制。本文使用3-氨基丙基三乙氧基硅烷对植入物表面进行氨基硅烷化,然后用0.25% w/v海藻酸盐与20 mM 1-乙基-3-(3-二甲基氨基丙基)碳二亚胺和N-羟基琥珀酰亚胺进行涂层,使A/G/BHT预凝胶均匀地分散并共价地附着在表面上。预凝胶中加入0.2M的氯化钠,使BHT均匀地混合在结构中,而不引起离子交联。然后,将涂层植入物冷冻干燥并储存。涂层显示出较高的内聚力和粘合力,在室温和正常湿度下有8个月的保质期。A/G/BHT能够包覆不规则形状的钛种植体。成骨细胞和内皮细胞可以在A/G/BHT上茁壮成长,并显示出极大的成骨和血管生成能力。此外,A/G/BHT保持了巨噬细胞的增殖能力,并在可迅速解决的免疫反应期间快速增殖。最后,A/G/BHT被证明能在2个月内诱导兔子股骨软骨模型中植入物的牢固整合。因此得出结论,A/G/BHT涂层可以作为一个多功能库,促进金属植入物快速且强固的骨整合。

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