Parry Joshua Alan, Olthof Maurits G L, Shogren Kristen L, Dadsetan Mahrokh, Van Wijnen Andre, Yaszemski Michael, Kakar Sanjeev
Department of Orthopaedic Surgery, Tissue Engineering and Biomaterials Laboratory, Mayo Clinic, Rochester, Minnesota.
Tissue Eng Part A. 2017 Apr;23(7-8):359-365. doi: 10.1089/ten.TEA.2016.0343. Epub 2017 Feb 9.
Anterior cruciate ligament (ACL) ruptures reconstructed with tendon grafts are commonly fixed with bioabsorbable implants, which are frequently complicated by incomplete bone filling upon degradation. Bone regeneration after ACL reconstruction could be enhanced by utilizing tissue engineering techniques and three-dimensional (3D) printing to create a porous bioabsorbable scaffold with delayed delivery of recombinant-human bone morphogenetic protein 2 (rhBMP-2). The first aim of this study was to design a 3D poly(propylene fumarate) (PPF) porous scaffold that maintained suitable pullout strength for future testing in a rabbit ACL reconstruction model. Our second aim was to determine the release kinetics of rhBMP-2 from PPF scaffolds that utilized both calcium-phosphate coatings and growth factor delivery on microspheres, both of which have been shown to decrease the initial burst release of rhBMP-2 and increase bone regeneration. To determine the degree of scaffold porosity that maintained suitable pullout strength, tapered scaffolds were fabricated with increasing porosity (0%, 20%, 35%, and 44%) and pullout testing was performed in a cadaveric rabbit ACL reconstruction model. Scaffolds were coated with carbonate hydroxyapatite (synthetic bone mineral [SBM]), and radiolabeled rhBMP-2 was delivered in four different experimental groups as follows: Poly(lactic-co-glycolic acid) microspheres only, microspheres and collagen (50:50), collagen only, and saline solution only. rhBMP-2 release was measured at day 1, 2, 4, 8, 16, and 32. The microsphere delivery groups had a smaller burst release and released a smaller percentage of rhBMP-2 over the 32 days than the collagen and saline only groups. In conclusion, a porous bioabsorbable scaffold with suitable strength for a rabbit ACL reconstruction was developed. Combining a synthetic bone mineral coating with microspheres had an additive effect, decreasing the initial burst release and cumulative release of rhBMP-2. Future studies need to evaluate this scaffold's fixation strength and bone filling capabilities in vivo compared to traditional bioabsorbable implants.
采用肌腱移植物重建前交叉韧带（ACL）时，通常使用生物可吸收植入物进行固定，而这些植入物在降解时常常伴有骨填充不完全的情况。利用组织工程技术和三维（3D）打印技术制造具有重组人骨形态发生蛋白2（rhBMP-2）延迟释放功能的多孔生物可吸收支架，可促进ACL重建后的骨再生。本研究的首要目标是设计一种3D聚富马酸丙二醇酯（PPF）多孔支架，使其在兔ACL重建模型中进行后续测试时能保持合适的拔出强度。我们的第二个目标是确定rhBMP-2从PPF支架中的释放动力学，该支架同时采用了磷酸钙涂层和微球上的生长因子递送，这两种方法均已证明可减少rhBMP-2的初始突释并促进骨再生。为了确定能保持合适拔出强度的支架孔隙率，制作了孔隙率递增（0%、20%、35%和44%）的锥形支架，并在尸体兔ACL重建模型中进行拔出测试。支架涂覆有碳酸羟基磷灰石（合成骨矿物质[SBM]），放射性标记的rhBMP-2在四个不同实验组中递送，如下所示：仅聚乳酸-羟基乙酸共聚物微球、微球和胶原蛋白（50:50）、仅胶原蛋白以及仅生理盐水溶液。在第1、2、4、8天、16天和32天测量rhBMP-2的释放量。与仅使用胶原蛋白和生理盐水的组相比，微球递送组的突释较小，并且在32天内释放的rhBMP-2百分比也较小。总之，开发出了一种具有适合兔ACL重建强度的多孔生物可吸收支架。将合成骨矿物质涂层与微球相结合具有累加效应，可减少rhBMP-2的初始突释和累积释放。未来的研究需要在体内评估该支架与传统生物可吸收植入物相比的固定强度和骨填充能力。
