School of Mechanical Engineering, Purdue University, West Lafayette, IN, USA.
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
Ann Biomed Eng. 2024 Jun;52(6):1638-1652. doi: 10.1007/s10439-024-03477-1. Epub 2024 Mar 12.
Subcutaneous tissue mechanics are important for drug delivery. Yet, even though this material is poroelastic, its mechanical characterization has focused on its hyperelastic response. Moreover, advancement in subcutaneous drug delivery requires effective tissue mimics such as hydrogels for which similar gaps of poroelastic data exist. Porcine subcutaneous samples and gelatin hydrogels were tested under confined compression at physiological conditions and strain rates of 0.01%/s in 5% strain steps with 2600 s of stress relaxation between loading steps. Force-time data were used in an inverse finite element approach to obtain material parameters. Tissues and gels were modeled as porous neo-Hookean materials with properties specified via shear modulus, effective solid volume fraction, initial hydraulic permeability, permeability exponent, and normalized viscous relaxation moduli. The constitutive model was implemented into an isogeometric analysis (IGA) framework to study subcutaneous injection. Subcutaneous tissue exhibited an initial spike in stress due to compression of the solid and fluid pressure buildup, with rapid relaxation explained by fluid drainage, and longer time-scale relaxation explained by viscous dissipation. The inferred parameters aligned with the ranges reported in the literature. Hydraulic permeability, the most important parameter for drug delivery, was in the range mm /(N s). With these parameters, IGA simulations showed peak stresses due to a 1-mL injection to reach 48.8 kPa at the site of injection, decaying after drug volume disperses into the tissue. The poro-hyper-viscoelastic neo-Hookean model captures the confined compression response of subcutaneous tissue and gelatin hydrogels. IGA implementation enables predictive simulations of drug delivery.
皮下组织力学对于药物输送很重要。然而，尽管这种材料是多孔弹性的，但它的力学特性主要集中在超弹性响应上。此外，皮下药物输送的进展需要有效的组织模拟物，例如水凝胶，而对于这些模拟物，同样存在多孔弹性数据的空白。在生理条件下，以 0.01%/s 的应变速率在 5%应变步长下进行限制压缩测试，在加载步之间有 2600 秒的应力松弛，测试猪的皮下样本和明胶水凝胶。利用力-时数据，采用逆有限元方法获得材料参数。组织和凝胶被建模为具有通过剪切模量、有效固体体积分数、初始水力渗透率、渗透率指数和归一化粘性松弛模量指定特性的多孔新胡克材料。本构模型被实现到等几何分析（IGA）框架中，以研究皮下注射。皮下组织由于固体和流体压力的积累而导致初始应力急剧上升，快速松弛是由于流体的排出，而较长时间尺度的松弛是由于粘性耗散引起的。推断出的参数与文献中报道的范围一致。水力渗透率是药物输送最重要的参数，范围为 mm /(N s)。利用这些参数，IGA 模拟显示，由于 1 毫升的注射，在注射部位的峰值应力达到 48.8 kPa，随着药物体积在组织中扩散，应力会逐渐下降。多孔超粘弹性新胡克模型可以捕捉皮下组织和明胶水凝胶的限制压缩响应。IGA 的实现可以实现药物输送的预测模拟。
