Department of Dentistry, Graduate School of Medicine, Korea University, 73 Goryeodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
e-Well Dental Hospital, Suite #214, Daebang B/D, Shindaebang-dong, Dongjak-gu, Seoul, 07056, Republic of Korea.
Tissue Eng Regen Med. 2020 Oct;17(5):607-624. doi: 10.1007/s13770-020-00257-5. Epub 2020 Aug 16.
The delivery of growth factors using a carrier system presents a promising and innovative tool in tissue engineering and dentistry today. Two of the foremost bioactive factors, bone morphogenetic protein-2 and vascular endothelial growth factor (VEGF), are widely applied using a ceramic scaffold. The aim of this study was to determine the use of hydroxyapatite microcarrier (MC) for dual delivery of osteogenic and angiogenic factors to accelerate hard tissue regeneration during the regenerative process.
Two MCs of different sizes were fabricated by emulsification of gelatin and alpha-tricalcium phosphate (α-TCP). The experimental group was divided based on the combination of MC size and growth factors. For investigating the in vitro properties, rat mesenchymal stem cells (rMSCs) were harvested from bone marrow of the femur and tibia. For in vivo experiments, MC with/without growth factors was applied into the standardized, 5-mm diameter defects, which were made bilaterally on the parietal bone of the rat. The animals were allowed to heal for 8 weeks, and samples were harvested and analyzed by micro-computed tomography and histology.
Improved proliferation of rat mesenchymal stem cells was observed with VEGF loaded MC. For osteogenic differentiation, dual growth factors delivered by MC showed higher osteogenic gene expression, alkaline phosphatse production and calcium deposition. The in vivo results revealed statistically significant increase in new bone formation when dual growth factors were delivered by MC. Dual growth factors administered on a calcium phosphate matrix showed significantly enhanced osteogenic potential.
We propose this system has potential clinical utility in providing solutions for craniofacial bone defects, with the added benefit of early availability.
在组织工程学和牙科学中，使用载体系统输送生长因子是一种很有前途和创新的工具。两种最重要的生物活性因子，骨形态发生蛋白-2 和血管内皮生长因子（VEGF），广泛应用于陶瓷支架。本研究旨在确定使用羟基磷灰石微载体（MC）双重输送成骨和血管生成因子，以加速再生过程中的硬组织再生。
通过明胶和α-磷酸三钙（α-TCP）的乳化作用制备了两种不同大小的 MC。实验组根据 MC 大小和生长因子的组合进行分组。为了研究体外特性，从股骨和胫骨骨髓中分离大鼠间充质干细胞（rMSCs）。为了进行体内实验，将含有/不含有生长因子的 MC 应用于双侧、直径为 5mm 的标准骨缺损中，该骨缺损位于大鼠顶骨上。允许动物愈合 8 周，然后通过微计算机断层扫描和组织学分析采集和分析样本。
负载 VEGF 的 MC 观察到大鼠间充质干细胞的增殖得到改善。对于成骨分化，MC 输送的双重生长因子显示出更高的成骨基因表达、碱性磷酸酶产生和钙沉积。体内结果表明，当 MC 输送双重生长因子时，新骨形成有统计学意义的增加。在磷酸钙基质上给予双重生长因子显示出明显增强的成骨潜力。
我们提出该系统具有为颅面骨缺损提供解决方案的潜在临床应用价值，并且具有早期可用性的额外优势。
