Banche-Niclot Federica, Licini Caterina, Montalbano Giorgia, Fiorilli Sonia, Mattioli-Belmonte Monica, Vitale-Brovarone Chiara
Department of Applied Science and Technology, Politecnico di Torino, 10129 Torino, Italy.
Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, 60126 Ancona, Italy.
Polymers (Basel). 2022 Feb 22;14(5):857. doi: 10.3390/polym14050857.
In bone regenerative strategies, the controlled release of growth factors is one of the main aspects for successful tissue regeneration. Recent trends in the drug delivery field increased the interest in the development of biodegradable systems able to protect and transport active agents. In the present study, we designed degradable poly(lactic-co-glycolic)acid (PLGA) nanocarriers suitable for the release of Transforming Growth Factor-beta 1 (TGF-β1), a key molecule in the management of bone cells behaviour. Spherical TGF-β1-containing PLGA (PLGA_TGF-β1) nanoparticles (ca.250 nm) exhibiting high encapsulation efficiency (ca.64%) were successfully synthesized. The TGF-β1 nanocarriers were subsequently combined with type I collagen for the fabrication of nanostructured 3D printed scaffolds able to mimic the TGF-β1 presence in the human bone extracellular matrix (ECM). The homogeneous hybrid formulation underwent a comprehensive rheological characterisation in view of 3D printing. The 3D printed collagen-based scaffolds (10 mm × 10 mm × 1 mm) successfully mimicked the TGF-β1 presence in human bone ECM as assessed by immunohistochemical TGF-β1 staining, covering ca.3.4% of the whole scaffold area. Moreover, the collagenous matrix was able to reduce the initial burst release observed in the first 24 h from about 38% for the PLGA_TGF-β1 alone to 14.5%, proving that the nanocarriers incorporation into collagen allows achieving sustained release kinetics.
在骨再生策略中，生长因子的控释是组织成功再生的主要方面之一。药物递送领域的最新趋势激发了人们对开发能够保护和运输活性剂的可生物降解系统的兴趣。在本研究中，我们设计了适用于释放转化生长因子-β1（TGF-β1）的可降解聚乳酸-乙醇酸共聚物（PLGA）纳米载体，TGF-β1是调控骨细胞行为的关键分子。成功合成了具有高包封率（约64%）的含TGF-β1的球形PLGA（PLGA_TGF-β1）纳米颗粒（约250 nm）。随后将TGF-β1纳米载体与I型胶原结合，制备出能够模拟人骨细胞外基质（ECM）中TGF-β1存在情况的纳米结构3D打印支架。鉴于3D打印，对均匀的混合制剂进行了全面的流变学表征。通过免疫组化TGF-β1染色评估，3D打印的胶原基支架（10 mm×10 mm×1 mm）成功模拟了人骨ECM中TGF-β1的存在情况，覆盖了整个支架面积的约3.4%。此外，胶原基质能够将最初24小时内观察到的突释从单独的PLGA_TGF-β1的约38%降低到14.5%，证明将纳米载体掺入胶原中可实现缓释动力学。
