Bouyer M, Garot C, Machillot P, Vollaire J, Fitzpatrick V, Morand S, Boutonnat J, Josserand V, Bettega G, Picart C
CEA, CNRS, Université de Grenoble Alpes, ERL5000 BRM, IRIG Institute, 17 Rue des Martyrs, F-38054, Grenoble, France.
CNRS and Grenoble Institute of Engineering, UMR5628, LMGP, 3 Parvis Louis Néel, F-38016, Grenoble, France.
Mater Today Bio. 2021 May 4;11:100113. doi: 10.1016/j.mtbio.2021.100113. eCollection 2021 Jun.
The reconstruction of large bone defects (12 cm) remains a challenge for clinicians. We developed a new critical-size mandibular bone defect model on a minipig, close to human clinical issues. We analyzed the bone reconstruction obtained by a 3D-printed scaffold made of clinical-grade polylactic acid (PLA), coated with a polyelectrolyte film delivering an osteogenic bioactive molecule (BMP-2). We compared the results (computed tomography scans, microcomputed tomography scans, histology) to the gold standard solution, bone autograft. We demonstrated that the dose of BMP-2 delivered from the scaffold significantly influenced the amount of regenerated bone and the repair kinetics, with a clear BMP-2 dose-dependence. Bone was homogeneously formed inside the scaffold without ectopic bone formation. The bone repair was as good as for the bone autograft. The BMP-2 doses applied in our study were reduced 20- to 75-fold compared to the commercial collagen sponges used in the current clinical applications, without any adverse effects. Three-dimensional printed PLA scaffolds loaded with reduced doses of BMP-2 may be a safe and simple solution for large bone defects faced in the clinic.
对于临床医生而言,大骨缺损(12厘米)的修复仍然是一项挑战。我们在小型猪身上建立了一种新的临界尺寸下颌骨缺损模型,该模型更贴近人类临床问题。我们分析了由临床级聚乳酸(PLA)制成的3D打印支架所实现的骨修复情况,该支架涂覆有递送成骨生物活性分子(骨形态发生蛋白-2,BMP-2)的聚电解质膜。我们将结果(计算机断层扫描、显微计算机断层扫描、组织学)与金标准解决方案——骨自体移植进行了比较。我们证明,从支架递送的BMP-2剂量显著影响再生骨量和修复动力学,具有明显的BMP-2剂量依赖性。骨在支架内均匀形成,无异位骨形成。骨修复情况与骨自体移植一样好。与当前临床应用中使用的商业胶原海绵相比,我们研究中应用的BMP-2剂量降低了20至75倍,且无任何不良影响。负载降低剂量BMP-2的3D打印PLA支架可能是临床上应对大骨缺损的一种安全且简单的解决方案。