Rapid prototyping amphiphilic polymer/hydroxyapatite composite scaffolds with hydration-induced self-fixation behavior.
Rapid prototyping amphiphilic polymer/hydroxyapatite composite scaffolds with hydration-induced self-fixation behavior.
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DOI：
10.1089/ten.tec.2014.0213
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发表时间：
2015-03
期刊：
影响因子：
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通讯作者：
A. Kutikov;A. Gurijala;Jie Song
中科院分区：
文献类型：
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作者：
A. Kutikov;A. Gurijala;Jie Song
阻碍快速原型生物材料广泛应用于组织工程应用的两个主要因素是对定制设计或昂贵的研究级三维(3D)打印机的要求，以及合适的热塑性生物材料的有限选择，这些材料表现出便于手术操作所需的物理特性和鼓励组织整合的生物学特性。设计合理的热塑性可生物降解两亲性聚合物可以表现出水化依赖的亲水性变化和硬化行为，这可能被利用来促进在生理组织环境中的手术输送/自固定支架。与传统的疏水聚酯相比，它们在与亲水的骨传导矿物共混方面也显示出显著的优势，并改善了骨组织工程应用的界面粘附性。在这里，我们展示了可生物降解的两亲性聚(D，L-乳酸)-聚乙二醇-聚(D，L-乳酸)(聚乳酸-聚乙二醇-聚乳酸)(PELA)三嵌段共聚物与羟基磷灰石(HA)的良好共混，并使用未经改进的消费级3D打印机制备了高质量的快速原型3D大孔复合支架。快速成型的HA-PELA复合支架和PELA对照组(没有HA)在水中膨胀(体积分别增加66%和44%)和硬化(压缩弹性系数分别增加1.38倍和4倍)。为了验证水化诱导的物理变化可以转化为支架在受限缺陷中的自固定性能的假设，设计了一种简单的体外拔出测试，以量化在干燥和潮湿状态下将这些支架从模拟的圆柱形缺陷中取出所需的峰值力。与我们的假设一致，PELA和HA-PELA支架的峰值固定力在水化时分别增加了6倍和15倍。此外，我们发现低污染的3D PELA抑制了NIH3T3成纤维细胞或骨髓基质细胞的附着，而HA-PELA容易支持细胞附着和成骨分化。最后，我们证明了快速成型双相PELA/HA-PELA支架用于潜在的引导骨再生的可行性，其中需要骨传导支架内部鼓励骨整合，而非粘连表面不鼓励纤维组织包裹。这项工作表明，通过将简便易行的快速成型方法与独特的生物材料设计相结合，可以开发出大孔率可控、生物微环境可空间定义和有用的处理特性的可生物降解复合支架。
Two major factors hampering the broad use of rapid prototyped biomaterials for tissue engineering applications are the requirement for custom-designed or expensive research-grade three-dimensional (3D) printers and the limited selection of suitable thermoplastic biomaterials exhibiting physical characteristics desired for facile surgical handling and biological properties encouraging tissue integration. Properly designed thermoplastic biodegradable amphiphilic polymers can exhibit hydration-dependent hydrophilicity changes and stiffening behavior, which may be exploited to facilitate the surgical delivery/self-fixation of the scaffold within a physiological tissue environment. Compared to conventional hydrophobic polyesters, they also present significant advantages in blending with hydrophilic osteoconductive minerals with improved interfacial adhesion for bone tissue engineering applications. Here, we demonstrated the excellent blending of biodegradable, amphiphilic poly(D,L-lactic acid)-poly(ethylene glycol)-poly(D,L-lactic acid) (PLA-PEG-PLA) (PELA) triblock co-polymer with hydroxyapatite (HA) and the fabrication of high-quality rapid prototyped 3D macroporous composite scaffolds using an unmodified consumer-grade 3D printer. The rapid prototyped HA-PELA composite scaffolds and the PELA control (without HA) swelled (66% and 44% volume increases, respectively) and stiffened (1.38-fold and 4-fold increases in compressive modulus, respectively) in water. To test the hypothesis that the hydration-induced physical changes can translate into self-fixation properties of the scaffolds within a confined defect, a straightforward in vitro pull-out test was designed to quantify the peak force required to dislodge these scaffolds from a simulated cylindrical defect at dry versus wet states. Consistent with our hypothesis, the peak fixation force measured for the PELA and HA-PELA scaffolds increased 6-fold and 15-fold upon hydration, respectively. Furthermore, we showed that the low-fouling 3D PELA inhibited the attachment of NIH3T3 fibroblasts or bone marrow stromal cells while the HA-PELA readily supported cellular attachment and osteogenic differentiation. Finally, we demonstrated the feasibility of rapid prototyping biphasic PELA/HA-PELA scaffolds for potential guided bone regeneration where an osteoconductive scaffold interior encouraging osteointegration and a nonadhesive surface discouraging fibrous tissue encapsulation is desired. This work demonstrated that by combining facile and readily translatable rapid prototyping approaches with unique biomaterial designs, biodegradable composite scaffolds with well-controlled macroporosities, spatially defined biological microenvironment, and useful handling characteristics can be developed.