Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300044, Taiwan.
Interdisciplinary Program of Life Science and Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan.
Biomater Adv. 2023 Oct;153:213562. doi: 10.1016/j.bioadv.2023.213562. Epub 2023 Jul 23.
The development of treatments for critical-sized bone defects has been considered an important topic in the biomedical field because of the high demand for transplantable bone grafts. Following the concept of tissue engineering, implantation of biocompatible porous scaffolds carrying cells and regulating factors is the most efficient strategy to stimulate clinical bone regeneration. With the advancement in the development of 3D-printing techniques, scaffolds with highly controllable architectures can be fabricated to further improve healing efficacies. However, challenges such as the limited biocompatibility of resin materials and poor cell-carrying capacities still exist in the application of current scaffolds. In this study, a novel biodegradable polymer, poly (ethylene glycol)-co-poly (glycerol sebacate) acrylate (PEGSA), was synthesized and blended with hydroxyapatite (HAP) nanoparticles to produce osteoinductive and photocurable resins for 3D printing. The composites were optimized and applied in the fabrication of gyroid scaffolds with biomimetic characteristics and high permeability, followed by the combination of bioactive hydrogels containing Wharton's jelly-derived mesenchymal stem cells (WJMSC) to increase the efficiency of cell delivery. The promotion of osteogenesis from 3D-printed scaffolds was confirmed in-vivo while the hybrid scaffolds were proven to be great platforms for WJMSC culture and differentiation in-vitro. These results indicate that the proposed hybrid systems, combining osteoinductive 3D-printed scaffolds and cell-laden hydrogels, have great potential for bone tissue engineering and are expected to be applied in the treatment of bone defects based on active tissue regeneration.
治疗临界尺寸骨缺损的方法一直是生物医学领域的一个重要课题，因为对可移植骨移植物的需求很高。在组织工程的概念之后，植入具有生物相容性的多孔支架，携带细胞和调节因子，是刺激临床骨再生的最有效策略。随着 3D 打印技术的发展，具有高度可控结构的支架可以被制造出来，以进一步提高愈合效果。然而，在当前支架的应用中，仍然存在树脂材料的生物相容性有限和细胞承载能力差等挑战。在本研究中，合成了一种新型可生物降解聚合物聚（乙二醇）-共-聚（甘油癸二酸酯）丙烯酸酯（PEGSA），并与羟基磷灰石（HAP）纳米颗粒混合，用于 3D 打印具有成骨诱导和光固化性能的树脂。对复合材料进行了优化，并应用于仿生特征和高渗透性的格子支架的制造，然后结合含有 Wharton 果冻衍生间充质干细胞（WJMSC）的生物活性水凝胶，以提高细胞输送效率。体内实验证实了 3D 打印支架的成骨促进作用，体外实验证明了杂交支架是 WJMSC 培养和分化的良好平台。这些结果表明，所提出的将成骨诱导 3D 打印支架与细胞负载水凝胶相结合的混合系统在骨组织工程中有很大的应用潜力，有望应用于基于主动组织再生的骨缺损治疗。
