Department of Mechanical Engineering, Stanford University, Stanford, CA 94305, USA.
J Theor Biol. 2012 Mar 21;297:166-75. doi: 10.1016/j.jtbi.2011.12.022. Epub 2012 Jan 4.
Skin displays an impressive functional plasticity, which allows it to adapt gradually to environmental changes. Tissue expansion takes advantage of this adaptation, and induces a controlled in situ skin growth for defect correction in plastic and reconstructive surgery. Stretches beyond the skin's physiological limit invoke several mechanotransduction pathways, which increase mitotic activity and collagen synthesis, ultimately resulting in a net gain in skin surface area. However, the interplay between mechanics and biology during tissue expansion remains unquantified. Here, we present a continuum model for skin growth that summarizes the underlying mechanotransduction pathways collectively in a single phenomenological variable, the strain-driven area growth. We illustrate the governing equations for growing biological membranes, and demonstrate their computational solution within a nonlinear finite element setting. In displacement-controlled equi-biaxial extension tests, the model accurately predicts the experimentally observed histological, mechanical, and structural features of growing skin, both qualitatively and quantitatively. Acute and chronic elastic uniaxial stretches are 25% and 10%, compared to 36% and 10% reported in the literature. Acute and chronic thickness changes are -28% and -12%, compared to -22% and -7% reported in the literature. Chronic fractional weight gain is 3.3, compared to 2.7 for wet weight and 3.3 for dry weight reported in the literature. In two clinical cases of skin expansion in pediatric forehead reconstruction, the model captures the clinically observed mechanical and structural responses, both acutely and chronically. Our results demonstrate that the field theories of continuum mechanics can reliably predict the mechanical manipulation of thin biological membranes by controlling their mechanotransduction pathways through mechanical overstretch. We anticipate that the proposed skin growth model can be generalized to arbitrary biological membranes, and that it can serve as a valuable tool to virtually manipulate living tissues, simply by means of changes in the mechanical environment.
皮肤表现出令人印象深刻的功能可塑性，使其能够逐渐适应环境变化。组织扩张利用了这种适应性，通过诱导受控的原位皮肤生长来纠正整形和重建手术中的缺陷。超出皮肤生理极限的拉伸会引发多种机械转导途径，增加有丝分裂活性和胶原合成，最终导致皮肤表面积的净增加。然而，在组织扩张过程中，力学和生物学之间的相互作用仍未被量化。在这里，我们提出了一个用于皮肤生长的连续体模型，该模型将潜在的机械转导途径概括为一个单一的现象变量，即应变驱动的面积生长。我们展示了用于生长生物膜的控制方程，并在非线性有限元设置中演示了它们的计算解决方案。在位移控制的等双轴拉伸试验中，该模型准确地预测了实验观察到的生长皮肤的组织学、力学和结构特征，无论是定性的还是定量的。与文献报道的 36%和 10%相比，急性和慢性弹性单轴拉伸分别为 25%和 10%。与文献报道的 -22%和 -7%相比，急性和慢性厚度变化分别为 -28%和 -12%。与文献报道的湿重 2.7 和干重 3.3 相比，慢性重量增加率为 3.3。在儿科额部重建中皮肤扩张的两个临床病例中，该模型捕捉到了急性和慢性的临床观察到的机械和结构反应。我们的结果表明，连续体力学的场论可以通过机械过度拉伸来可靠地预测对薄生物膜的机械操纵，从而控制其机械转导途径。我们预计所提出的皮肤生长模型可以推广到任意生物膜，并可以作为一种有价值的工具，通过改变机械环境来虚拟地操纵活体组织。
