MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Complex Tissue Regeneration Department, Maastricht, the Netherlands.
Department of Applied Science and Technology, Politecnico di Torino, Torino, Italy.
Biomater Adv. 2023 Jun;149:213406. doi: 10.1016/j.bioadv.2023.213406. Epub 2023 Mar 29.
The combination of biomaterials and bioactive particles has shown to be a successful strategy to fabricate electrospun scaffolds for bone tissue engineering. Among the range of bioactive particles, hydroxyapatite and mesoporous bioactive glasses (MBGs) have been widely used for their osteoconductive and osteoinductive properties. Yet, the comparison between the chemical and mechanical characteristics as well as the biological performances of these particle-containing scaffolds have been characterized to a limited extent. In this work, we fabricated PEOT/PBT-based composite scaffolds incorporating either nanohydroxyapatite (nHA), strontium-containing nanohydroxyapatite (nHA_Sr) or MBGs doped with strontium ions up to 15 wt./vol% and 12,5 wt./vol% for nHA and MBG, respectively. The composite scaffolds presented a homogeneous particle distribution. Morphological, chemical and mechanical analysis revealed that the introduction of particles into the electrospun meshes caused a decrease in the fiber diameter and mechanical properties, yet maintaining the hydrophilic nature of the scaffolds. The Sr release profile differed according to the considered system, observing a 35-day slowly decreasing release from strontium-containing nHA scaffolds, whereas MBG-based scaffolds showed a strong burst release in the first week. In vitro, culture of human bone marrow-derived mesenchymal stromal cells (hMSCs) on composite scaffolds demonstrated excellent cell adhesion and proliferation. In maintenance and osteogenic media, all composite scaffolds showed high mineralization as well as expression of Col I and OCN compared to PEOT/PBT scaffolds, suggesting their ability to boost bone formation even without osteogenic factors. The presence of strontium led to an increase in collagen secretion and matrix mineralization in osteogenic medium, while gene expression analysis showed that hMSCs cultured on nHA-based scaffolds had a higher expression of OCN, ALP and RUNX2 compared to cells cultured on nHA_Sr scaffolds in osteogenic medium. Yet, cells cultured on MBGs-based scaffolds showed a higher gene expression of COL1, ALP, RUNX2 and BMP2 in osteogenic medium compared to nHA-based scaffolds, which is hypothesized to lead to high osteoinductivity in long term cultures.
生物材料和生物活性颗粒的组合已被证明是制造用于骨组织工程的电纺支架的成功策略。在各种生物活性颗粒中,羟基磷灰石和中孔生物活性玻璃(MBG)由于其骨传导性和骨诱导性而被广泛使用。然而,这些含颗粒支架的化学和机械特性以及生物学性能的比较在很大程度上还没有得到描述。在这项工作中,我们制备了基于聚(醚醚酮)/聚对苯二甲酸丁二醇酯(PEOT/PBT)的复合支架,其中掺入了纳米羟基磷灰石(nHA)、含锶的纳米羟基磷灰石(nHA_Sr)或 MBG,分别高达 15wt.%/体积%和 12.5wt.%/体积%。复合支架呈现均匀的颗粒分布。形态、化学和机械分析表明,将颗粒引入电纺网中会导致纤维直径和机械性能降低,但保持支架的亲水性。Sr 的释放曲线因所考虑的系统而异,观察到含锶 nHA 支架的 Sr 释放呈 35 天缓慢下降,而 MBG 基支架在第一周内表现出强烈的突释。在体外,人骨髓间充质基质细胞(hMSC)在复合支架上的培养表现出良好的细胞粘附和增殖。在维持和成骨培养基中,与 PEOT/PBT 支架相比,所有复合支架均具有高矿化以及 Col I 和 OCN 的表达,表明它们即使没有成骨因子也能促进骨形成。锶的存在导致成骨培养基中胶原分泌和基质矿化增加,而基因表达分析表明,在成骨培养基中,与 nHA_Sr 支架上培养的细胞相比,在 nHA 支架上培养的 hMSC 具有更高的 OCN、ALP 和 RUNX2 表达。然而,在成骨培养基中,与 nHA 基支架相比,在 MBG 基支架上培养的细胞表现出更高的 COL1、ALP、RUNX2 和 BMP2 基因表达,这被假设为在长期培养中具有高骨诱导性。