Meloni Gregory R, Fisher Matthew B, Stoeckl Brendan D, Dodge George R, Mauck Robert L
1 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
2 Translational Musculoskeletal Research Center, Corporal Michael J Crescenz VA Medical Center , Philadelphia, Pennsylvania.
Tissue Eng Part A. 2017 Jul;23(13-14):663-674. doi: 10.1089/ten.tea.2016.0191. Epub 2017 Apr 14.
Cartilage tissue engineering is emerging as a promising treatment for osteoarthritis, and the field has progressed toward utilizing large animal models for proof of concept and preclinical studies. Mechanical testing of the regenerative tissue is an essential outcome for functional evaluation. However, testing modalities and constitutive frameworks used to evaluate in vitro grown samples differ substantially from those used to evaluate in vivo derived samples. To address this, we developed finite element (FE) models (using FEBio) of unconfined compression and indentation testing, modalities commonly used for such samples. We determined the model sensitivity to tissue radius and subchondral bone modulus, as well as its ability to estimate material parameters using the built-in parameter optimization tool in FEBio. We then sequentially tested agarose gels of 4%, 6%, 8%, and 10% weight/weight using a custom indentation platform, followed by unconfined compression. Similarly, we evaluated the ability of the model to generate material parameters for living constructs by evaluating engineered cartilage. Juvenile bovine mesenchymal stem cells were seeded (2 × 10 cells/mL) in 1% weight/volume hyaluronic acid hydrogels and cultured in a chondrogenic medium for 3, 6, and 9 weeks. Samples were planed and tested sequentially in indentation and unconfined compression. The model successfully completed parameter optimization routines for each testing modality for both acellular and cell-based constructs. Traditional outcome measures and the FE-derived outcomes showed significant changes in material properties during the maturation of engineered cartilage tissue, capturing dynamic changes in functional tissue mechanics. These outcomes were significantly correlated with one another, establishing this FE modeling approach as a singular method for the evaluation of functional engineered and native tissue regeneration, both in vitro and in vivo.
软骨组织工程正成为治疗骨关节炎的一种有前景的方法，并且该领域已朝着利用大型动物模型进行概念验证和临床前研究发展。对再生组织进行力学测试是功能评估的一项重要指标。然而，用于评估体外培养样本的测试方式和本构框架与用于评估体内衍生样本的方式有很大不同。为了解决这个问题，我们开发了无侧限压缩和压痕测试的有限元（FE）模型（使用FEBio），这些是常用于此类样本的测试方式。我们确定了模型对组织半径和软骨下骨模量的敏感性，以及其使用FEBio中的内置参数优化工具估计材料参数的能力。然后，我们使用定制的压痕平台依次测试了重量/重量比为4%、6%、8%和10%的琼脂糖凝胶，随后进行无侧限压缩。同样，我们通过评估工程软骨来评估该模型生成活体构建物材料参数的能力。将幼年牛间充质干细胞（2×10个细胞/毫升）接种到1%重量/体积的透明质酸水凝胶中，并在软骨生成培养基中培养3、6和9周。将样本刨平并依次进行压痕和无侧限压缩测试。该模型成功地为脱细胞和基于细胞的构建物的每种测试方式完成了参数优化程序。传统的结果测量和有限元得出的结果表明，工程软骨组织成熟过程中材料特性发生了显著变化，捕捉到了功能组织力学的动态变化。这些结果彼此之间显著相关，确立了这种有限元建模方法作为评估体外和体内功能工程化及天然组织再生的单一方法。
