Kim Hyunjae, Kim Sungtae, Han Hee-Seung, Kim Woo-Jin, Cho Young-Dan
Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
Department of Periodontology, Korea University Anam Hospital, Seoul, Republic of Korea.
Sci Rep. 2025 Jul 24;15(1):27002. doi: 10.1038/s41598-025-12497-3.
The sustained release and bone tissue-specific localization of bone morphogenetic protein 2 (BMP-2) are crucial factors in overcoming the shortcomings in its clinical use. In a previous study, we introduced a bone-targeted, lipoplex-loaded, three-dimensional (3D) bioprinted bilayer scaffold, termed polycaprolactone-bioink-nanoparticle (PBN). We confirmed the bone-specific and sustained release of BMP-2 with PBN in silico and in vitro and demonstrated improved bone formation in vivo. In this study, we evaluated the bone-regenerative effect of PBN combined with bone-inducing drugs in the beagle 3-wall defect model, aiming to facilitate their stable and active application in clinical settings. Surgical defects were created on both sides of the beagle mandible after 4 weeks of teeth extraction (P2, P3, and P4), assigning four groups: (1) control, no scaffold; (2) BMP-2, BMP-2-loaded collagen; (3) PBN/BMP/5-aza-dC, BMP-2, 5-aza-2'-deoxycytidine (5-aza-dC) loaded PBN scaffold; and (4) PBN/5-aza-dC, 5-aza-dC-loaded PBN scaffold. At 4 and 8 weeks postoperatively, the beagles were sacrificed, and radiographic and histological analyses were performed. The micro-computed tomography analysis revealed that the PBN/BMP/5-aza-dC and PBN/5-aza-dC groups showed significant increases in volume density and bone mineral density between 4 and 8 weeks postoperatively (p < 0.05). The BMP-2 and PBN/BMP/5-aza-dC groups showed significantly more mineralized tissue 4 weeks postoperatively, and the largest amount of mineralized tissue was detected after 8 weeks. Based on these results, we suggest that the PBN scaffold would be a good carrier for bone-inducing drugs with bone-tissue specificity and sustained release, especially BMP-2, to reduce clinical side effects.
骨形态发生蛋白2（BMP-2）的缓释及骨组织特异性定位是克服其临床应用缺陷的关键因素。在之前的一项研究中，我们引入了一种骨靶向、负载脂质体复合物的三维（3D）生物打印双层支架，称为聚己内酯-生物墨水-纳米颗粒（PBN）。我们在计算机模拟和体外实验中证实了PBN对BMP-2的骨特异性和缓释作用，并在体内证明了其促进骨形成的效果。在本研究中，我们在比格犬三壁骨缺损模型中评估了PBN与骨诱导药物联合使用的骨再生效果，旨在促进它们在临床环境中的稳定和有效应用。在拔牙4周后（P2、P3和P4），在比格犬下颌骨两侧制造手术缺损，分为四组：（1）对照组，无支架；（2）BMP-2组，负载BMP-2的胶原蛋白；（3）PBN/BMP/5-aza-dC组，负载BMP-2和5-氮杂-2'-脱氧胞苷（5-aza-dC）的PBN支架；（4）PBN/5-aza-dC组，负载5-aza-dC的PBN支架。术后4周和8周，处死比格犬并进行影像学和组织学分析。微计算机断层扫描分析显示，PBN/BMP/5-aza-dC组和PBN/5-aza-dC组在术后4至8周时体积密度和骨矿物质密度显著增加（p < 0.05）。BMP-2组和PBN/BMP/5-aza-dC组在术后4周时矿化组织明显更多，术后8周时检测到的矿化组织量最大。基于这些结果，我们认为PBN支架将是一种具有骨组织特异性和缓释功能的骨诱导药物的良好载体，尤其是BMP-2，可减少临床副作用。
