Biomaterials Research Group, Bioengineering Program, Engineering Faculty, University of Antioquia, Medellin, Colombia; Department of Chemical Engineering, Northeastern University, Boston, MA, USA.
Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba, Sao Jose dos Campos, SP, Brazil; Department of Chemical Engineering, Northeastern University, Boston, MA, USA.
Acta Biomater. 2019 Jan 1;83:425-434. doi: 10.1016/j.actbio.2018.10.023. Epub 2018 Oct 17.
The combination of kappa-carrageenan (κ-CG) and hydroxyapatite (HA) to generate a bone substitute material has been underexplored to date. Carrageenans (CGs) have remarkable characteristics such as biocompatibility, hydrophilicity, and structural similarities with natural glycosaminoglycans (GAGs), and they have demonstrated the ability to stimulate cellular adhesion and proliferation. Hydroxyapatite nanoparticles have been one of the most investigated materials for bone regeneration due to their excellent biocompatibility, bioactivity and osteoconductivity. In particular, this study presents an approach for the preparation of new bioactive composites of κ-CG/nHA for numerous bone regeneration applications. We performed a set of in vitro experiments to evaluate the influence of the bone substitutes on human osteoblasts. Cell culture studies indicated that all samples tested were cytocompatible. Relative to control substrates, cellular attachment and proliferation were better on all the scaffold surfaces that were tested. The S2 and S3 samples, those permeated by 1.5 and 2.5 wt% of CG, respectively, exhibited an enhancement in cell spreading capacity compared to the S1 test materials which were comprised of 1 wt% of CG. Excellent osteoblast viability and adhesion were observed for each of the tested materials. Additionally, the bone substitutes developed for this study presented a distinct osteoconductive environment. Data supporting this claim were derived from alkaline phosphatase (ALP) and calcium deposition analyses, which indicated that, compared to the control species, ALP expression and calcium deposition were both improved on test κ-CG/nHA surfaces. In summary, the injectable bone substitute developed here demonstrated great potential for numerous bone regeneration applications, and thus, should be studied further. STATEMENT OF SIGNIFICANCE: The novelty of this work lies in the determination of the in vitro cytocompatibility behavior of carrageenan and hydroxyapatite composite materials used as injectable bone substitutes. This injectable biomaterial can fill in geometric complex defects, and it displays bioactivity as well as high bone regeneration capacity. In this study, we evaluated the behaviors of osteoblast cells in contact with the scaffolds, including cellular adhesion and proliferation, cellular metabolism, and mineralization on the fabricated injectable bone substitutes. The results show than the carrageenan and hydroxyapatite substitutes provided a biomaterial with a great capacity for promoting cellular growth, adhesion, and proliferation, as well as contributing an osteoinductive environment for osteoblast differentiation and osteogenesis.
κ-卡拉胶（κ-CG）和羟基磷灰石（HA）的组合生成了一种骨替代材料，目前对此研究还较少。卡拉胶（CGs）具有良好的生物相容性、亲水性和与天然糖胺聚糖（GAGs）的结构相似性，并且已显示出刺激细胞黏附和增殖的能力。羟基磷灰石纳米粒子因其良好的生物相容性、生物活性和骨传导性而成为最受研究的骨再生材料之一。特别是，本研究提出了一种制备新的κ-CG/nHA 生物活性复合材料的方法，用于多种骨再生应用。我们进行了一系列体外实验来评估骨替代物对人成骨细胞的影响。细胞培养研究表明，所有测试的样本均具有细胞相容性。与对照基底相比，在所有测试的支架表面上，细胞附着和增殖情况更好。分别渗透 1.5 和 2.5wt%CG 的 S2 和 S3 样品与包含 1wt%CG 的 S1 测试材料相比，显示出细胞扩展能力增强。每个测试材料都观察到良好的成骨细胞活力和黏附性。此外，本研究中开发的骨替代物呈现出独特的骨诱导环境。支持这一说法的数据来自碱性磷酸酶（ALP）和钙沉积分析，表明与对照物种相比，ALP 表达和钙沉积在测试的 κ-CG/nHA 表面均得到改善。总之，这里开发的可注射骨替代物在许多骨再生应用中具有巨大的潜力，因此应进一步研究。意义声明：这项工作的新颖之处在于确定用作可注射骨替代物的卡拉胶和羟基磷灰石复合材料的体外细胞相容性行为。这种可注射生物材料可以填充几何复杂的缺陷，并且具有生物活性和高骨再生能力。在这项研究中，我们评估了与支架接触的成骨细胞的行为，包括在制备的可注射骨替代物上的细胞黏附、增殖、细胞代谢和矿化。结果表明，卡拉胶和羟基磷灰石替代物提供了一种具有促进细胞生长、黏附和增殖能力的生物材料，并为成骨细胞分化和骨生成提供了一个诱导性的环境。
