Aligned Gelatin Microribbon Scaffolds with Hydroxyapatite Gradient for Engineering the Bone-Tendon Interface.
Aligned Gelatin Microribbon Scaffolds with Hydroxyapatite Gradient for Engineering the Bone-Tendon Interface.
复制标题
具有羟基磷灰石梯度的对齐明胶微带支架用于工程骨-肌腱界面。
DOI：
10.1089/ten.tea.2021.0099
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发表时间：
2022
影响因子：
--
通讯作者：
Yang,Fan
中科院分区：
文献类型：
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作者：
Stanton,AliceE;Tong,Xinming;Jing,SerenaL;Behn,Anthony;Storaci,Hunter;Yang,Fan
骨-肌腱界面损伤，如肩袖和前交叉韧带撕裂，是常见的肌肉骨骼损伤，但有效的修复方法仍然难以捉摸。使用细胞和生物材料的组织工程方法为工程化骨-肌腱界面提供了一个有前途的潜在解决方案，但以前的策略需要接种多种细胞类型和使用多相支架来实现区域特异性组织表型。此外，在三维（3D）中模拟天然骨-肌腱界面中存在的对齐组织形态仍然具有挑战性。为了促进临床转化，使用单个细胞源和具有对准线索的连续支架来工程化骨-肌腱界面将更有吸引力，但以前尚未实现。为了解决这些未满足的需求，在这项研究中，我们开发了一种具有羟基磷灰石纳米颗粒（HA-np）梯度的对齐明胶微载体（μRB）水凝胶支架，用于引导人间充质干细胞（hMSC）的区域特异性分化，以模拟骨-肌腱界面。我们证明，对齐的μ RB导致细胞在3D中对齐，HA梯度诱导间充质干细胞的区域特异性分化，类似于骨-肌腱界面处的过渡。在暴露于成骨因子之前的短软骨形成引发进一步增强了骨-软骨-肌腱过渡的模仿，从而显著改善了所得组织的拉伸模量。总之，具有HA梯度的对齐的明胶μRBs与优化的可溶性因子结合，可能为使用单细胞来源的工程化骨-肌腱界面提供一种有前途的策略。影响声明我们的3D大孔微载体水凝胶平台具有与羟基磷灰石纳米颗粒分区整合的对齐线索，能够在连续支架内实现骨-肌腱界面的分化。虽然迄今为止大多数界面支架依赖于复合材料和多层方法，但我们提出了一种利用单细胞来源的连续支架。生态位线索与人类间充质干细胞（hMSC）培养物的协同作用导致培养物中拉伸模量增加超过45倍。我们进一步证明，向软骨细胞系诱导hMSCs可以增强分化成骨。依赖于单个细胞来源可以增强区域整合和支架完整性，沿着实际益处。
Injuries of the bone-to-tendon interface, such as rotator cuff and anterior cruciate ligament tears, are prevalent musculoskeletal injuries, yet effective methods for repair remain elusive. Tissue engineering approaches that use cells and biomaterials offer a promising potential solution for engineering the bone–tendon interface, but previous strategies require seeding multiple cell types and use of multiphasic scaffolds to achieve zonal-specific tissue phenotype. Furthermore, mimicking the aligned tissue morphology present in native bone–tendon interface in three-dimensional (3D) remains challenging. To facilitate clinical translation, engineering bone–tendon interface using a single cell source and one continuous scaffold with alignment cues would be more attractive but has not been achieved before. To address these unmet needs, in this study, we develop an aligned gelatin microribbon (μRB) hydrogel scaffold with hydroxyapatite nanoparticle (HA-np) gradient for guiding zonal-specific differentiation of human mesenchymal stem cell (hMSC) to mimic the bone–tendon interface. We demonstrate that aligned μRBs led to cell alignment in 3D, and HA gradient induced zonal-specific differentiation of mesenchymal stem cells that resemble the transition at the bone–tendon interface. Short chondrogenic priming before exposure to osteogenic factors further enhanced the mimicry of bone–cartilage–tendon transition with significantly improved tensile moduli of the resulting tissues. In summary, aligned gelatin μRBs with HA gradient coupled with optimized soluble factors may offer a promising strategy for engineering bone–tendon interface using a single cell source.Impact statementOur 3D macroporous microribbon hydrogel platform with alignment cues zonally integrated with hydroxyapatite nanoparticles enables differentiation across the bone-tendon interface within a continuous scaffold. While most interfacial scaffolds heretofore rely on composites and multilayer approaches, we present a continuous scaffold utilizing a single cell source. The synergy of niche cues with human mesenchymal stem cell (hMSC) culture leads to an over 45-fold enhancement in tensile modulus in culture. We further demonstrate that priming hMSCs towards the chondrogenic lineage can enhance the differential osteogenesis. Relying on a single cell source could enhance zone integration and scaffold integrity, along with practical benefits.