Department of Nanobiomedical Science, Dankook University, Cheonan 31116, Republic of Korea.
Department of Advanced Materials, Hannam University, Daejeon 34054, Republic of Korea.
Biomacromolecules. 2020 Dec 14;21(12):4795-4805. doi: 10.1021/acs.biomac.0c00992. Epub 2020 Oct 2.
Although biological therapies based on growth factors and transplanted cells have demonstrated some positive outcomes for intervertebral disc (IVD) regeneration, repeated injection of growth factors and cell leakage from the injection site remain considerable challenges for human therapeutic use. Herein, we prepare human bone marrow-derived mesenchymal stem cells (BMSCs) and transforming growth factor-β3 (TGF-β3)-loaded porous particles with a unique leaf-stack structural morphology (LSS particles) as a combination bioactive delivery matrix for degenerated IVD. The LSS particles are fabricated with clinically acceptable biomaterials (polycaprolactone and tetraglycol) and procedures (simple heating and cooling). The LSS particles allow sustained release of TGF-β3 for 18 days and stable cell adhesiveness without additional modifications of the particles. On the basis of and studies, it was observed that the BMSCs/TGF-β3-loaded LSS particles can provide a suitable milieu for chondrogenic differentiation of BMSCs and effectively induce IVD regeneration in a beagle dog model. Thus, therapeutically loaded LSS particles offer the promise of an effective bioactive delivery system for regeneration of various tissues including IVD.
尽管基于生长因子和移植细胞的生物疗法已经证明在椎间盘（IVD）再生方面取得了一些积极的结果，但生长因子的重复注射和细胞从注射部位泄漏仍然是人类治疗应用的重大挑战。在此，我们制备了负载转化生长因子-β3（TGF-β3）的人骨髓间充质干细胞（BMSCs）和具有独特叶堆叠结构形态（LSS 颗粒）的多孔颗粒，作为用于退化的 IVD 的组合生物活性递药基质。LSS 颗粒由临床可接受的生物材料（聚己内酯和四甘醇）和程序（简单的加热和冷却）制成。LSS 颗粒允许 TGF-β3 持续释放 18 天，并保持稳定的细胞粘附性，而无需对颗粒进行额外的修饰。基于 和 研究，观察到负载 BMSCs/TGF-β3 的 LSS 颗粒可为 BMSCs 的软骨分化提供合适的微环境，并有效诱导犬模型的 IVD 再生。因此，负载治疗剂的 LSS 颗粒有望成为一种有效的生物活性递药系统，可用于包括 IVD 在内的各种组织的再生。
