Park Soomin, Pascal Alexander B, Eisig Sidney B, Feng Meng, Jeong Hun Jin, Zhu Elen, Zhang Emily, Lee Chang Hun
Center for Dental and Craniofacial Research, College of Dental Medicine, Columbia University Medical Center, New York, NY 10032, USA.
Section of Hospital Dentistry/Division of Oral and Maxillofacial Surgery, College of Dental Medicine, Columbia University Medical Center, New York, NY 10032, USA.
Biomater Res. 2025 May 30;29:0199. doi: 10.34133/bmr.0199. eCollection 2025.
Each year, 1 in every 700 babies is born with an orofacial cleft in the USA. Despite a well-established protocol for early cleft repair, the alveolar cleft persists during craniofacial growth. Current surgical treatments with bone grafts for alveolar cleft often provide inadequate nasal base support and insufficient alveolar bone volume for permanent tooth eruption. Here, we developed 3-dimensionally printed polycaprolactone scaffolds with controlled delivery of icariin (ICA) to facilitate bone reconstruction. After establishing a reliable fabrication process, we determined the optimal loading dose and release kinetics of ICA for induced osteogenic differentiation of bone marrow mesenchymal stem/progenitor cells and mineralized tissue formation in vitro. Then, the ICA-releasing polycaprolactone scaffolds with the preoptimized dose were implanted into rats with full-thickness maxillary defects. Up to 8 weeks, micro-computed tomography analyses demonstrated significantly accelerated bone healing and defect closure with an ICA-releasing scaffold compared to scaffold alone and defect controls. Histology consistently confirmed the formation of dense woven bone with ICA-releasing scaffolds in contrast to unclosed gaps and soft tissue infiltration in controls. Our findings suggest the significant potential of ICA-releasing 3-dimensionally printed scaffolds to serve as a patient-focused and custom-built bone graft to improve the clinical outcome of alveolar cleft reconstruction.
在美国，每年每700名婴儿中就有1名出生时患有口面部裂隙。尽管有完善的早期腭裂修复方案，但牙槽裂在颅面生长过程中仍然存在。目前用于牙槽裂骨移植的手术治疗通常提供的鼻基底支撑不足，且牙槽骨体积不足以支持恒牙萌出。在此，我们开发了三维打印的聚己内酯支架，可控制淫羊藿苷（ICA）的释放，以促进骨重建。在建立了可靠的制造工艺后，我们确定了ICA诱导骨髓间充质干/祖细胞成骨分化和体外矿化组织形成的最佳负载剂量和释放动力学。然后，将预先优化剂量的释放ICA的聚己内酯支架植入全层上颌骨缺损的大鼠体内。长达8周的微型计算机断层扫描分析表明，与单独使用支架和缺损对照组相比，释放ICA的支架显著加速了骨愈合和缺损闭合。组织学结果一致证实，释放ICA的支架形成了致密的编织骨，而对照组则存在未闭合的间隙和软组织浸润。我们的研究结果表明，释放ICA的三维打印支架具有巨大潜力，可作为以患者为中心的定制骨移植材料，改善牙槽裂重建的临床效果。
