Nicodemus G D, Shiplet K A, Kaltz S R, Bryant S J
Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309, USA.
Biotechnol Bioeng. 2009 Feb 15;102(3):948-59. doi: 10.1002/bit.22105.
Biodegradable hydrogels are attractive 3D environments for cell and tissue growth. In cartilage tissue engineering, mechanical stimulation has been shown to be an important regulator in promoting cartilage development. However, the impact of mechanical loading on the gel degradation kinetics has not been studied. In this study, we examined hydrolytically labile gels synthesized from poly(lactic acid)-b-poly(ethylene glycol)-b-poly-(lactic acid) dimethacrylate macromers, which have been used for cartilage tissue engineering. The gels were subject to physiological loading conditions in order to examine the effects of loading on hydrogel degradation. Initially, hydrogels were formed with two different cross-linking densities and subject to a dynamic compressive strain of 15% at 0.3, 1, or 3 Hz. Degradation behavior was assessed by mass loss, equilibrium swelling and compressive modulus as a function of degradation time. From equilibrium swelling, the pseudo-first-order reaction rate constants were determined as an indication of degradation kinetics. The application of dynamic loading significantly enhanced the degradation time for the low cross-linked gels (P < 0.01) while frequency showed no statistical differences in degradation rates or bulk erosion profiles. In the higher cross-linked gels, a 3 Hz dynamic strain significantly increased the degradation kinetics resulting in an overall faster degradation time by 6 days compared to gels subject to the 0.3 and 1 Hz loads (P < 0.0001). The bioreactor set-up also influenced overall degradation behavior where the use of impermeable versus permeable platens resulted in significantly lower degradation rate constants for both cross-linked gels (P < 0.001). The compressive modulus exponentially decreased with degradation time under dynamic loading. Together, our findings indicate that both loading regime and the bioreactor setup influence degradation and should be considered when designing and tuning a biodegradable hydrogel where mechanical stimulation is employed.
可生物降解水凝胶是用于细胞和组织生长的有吸引力的三维环境。在软骨组织工程中，机械刺激已被证明是促进软骨发育的重要调节因素。然而，机械加载对凝胶降解动力学的影响尚未得到研究。在本研究中，我们研究了由聚（乳酸）-b-聚（乙二醇）-b-聚（乳酸）二甲基丙烯酸酯大分子单体合成的水解不稳定凝胶，这些凝胶已用于软骨组织工程。使凝胶处于生理加载条件下，以研究加载对水凝胶降解的影响。最初，形成具有两种不同交联密度的水凝胶，并在0.3、1或3Hz下施加15%的动态压缩应变。通过质量损失、平衡溶胀和压缩模量作为降解时间的函数来评估降解行为。从平衡溶胀中，确定拟一级反应速率常数作为降解动力学的指标。动态加载的应用显著延长了低交联凝胶的降解时间（P<0.01），而频率在降解速率或整体侵蚀曲线方面没有统计学差异。在较高交联的凝胶中，3Hz的动态应变显著加快了降解动力学，与承受0.3和1Hz负载的凝胶相比，总体降解时间加快了6天（P<0.0001）。生物反应器的设置也影响了整体降解行为，其中使用不可渗透与可渗透压板导致两种交联凝胶的降解速率常数显著降低（P<0.001）。在动态加载下，压缩模量随降解时间呈指数下降。总之，我们的研究结果表明，加载方式和生物反应器设置都会影响降解，在设计和调整采用机械刺激的可生物降解水凝胶时应予以考虑。
