(94c) Agent-Based Modeling of Porous Scaffold Degradation and Vascularization: Optimal Scaffold Design Based on Architecture and Degradation Dynamics

Agent-based modeling of porous scaffold degradation and vascularization: Optimal scaffold design based on architecture and degradation dynamics

Hamidreza Mehdizadeh ^a, Elif S. Bayrak ^a, Chenlin Lu ^a, Sami Somo ^a, Banu Akar ^a, Eric M. Brey ^b,c, Ali Cinar ^a,*

^a Department of Chemical and Biological Engineering, Illinois Institute of Technology, 10 W

33rd St, Suite 127, ChBE desk, Chicago, IL 60616, USA

^b Department of Biomedical Engineering, Illinois Institute of Technology, Suite 314, 3255 S

Dearborn St, Chicago, IL 60616, USA

^c Research Service, Hines Veterans Administration Hospital, Hines, IL, USA

Biomaterial scaffolds serve as substrates for angiogenesis and tissue growth by providing essential mechanical and structural support required for appropriate cell function and morphogenesis. The degradation behavior of scaffolds affects angiogenesis significantly since it changes the porous structure and mechanical properties of the scaffold dynamically over time. It is important for the scaffold to degrade at a balanced rate and maintain the scaffold integrity during tissue formation. One problem that may arise during the tissue regeneration process is the mechanical failure of the tissue engineering construct as a result of fast scaffold degradation before production of new tissue.

An agent-based model (ABM) of biomaterial scaffold vascularization [1] is extended to consider the effects of scaffold degradation on the dynamics of angiogenesis. A statistical model developed by Metters et al. to describe the bulk degradation of PLA-b-PEG-b-PLA hydrogel is applied to incorporate scaffold degradation factors into the model [2]. The modified ABM is focused on the combined effects of scaffold porous architecture and degradation on vascularization process. The degradation rate of scaffolds can be manipulated and altered based on the rate degree of crosslinking, hydrolysis reaction rate constant, polymer composition, and/or polymer concentration. A multi-layer scaffold model having regions with different degradation rates within the scaffold structure was designed. The ABM of the multi-layer scaffold, was used to explore the optimal conditions for scaffold vascularization.

 The simulation results indicate that scaffold degradation plays an important role in angiogenesis. Specifically, it improves vascularization more when degradation rate is higher and scaffold porosity is lower. Simulation with multi-layer scaffold model shows that vascularization was successfully continued after the previous scaffold layer was fully disintegrated because a considerable portion of the present layer was still remaining and providing sufficient mechanical strength and cell-attachment sites for angiogenesis. In general, it is observed that degradation can be utilized as a means of enhancing vascularization and the multi-layer scaffold model can further optimize the scaffold vascularization without losing mechanical support of the biomaterial scaffolds. Simulations show the flexibility of the developed ABM and exemplify the types of investigation it enables. These results can be used in combination with experimental research to design optimal scaffold structures.

Reference:

[1]        H. Mehdizadeh, S. Somo, E.S. Bayrak, E.M. Brey, A. Cinar, “Three-dimensional modeling of   angiogenesis in porous biomaterial.” Biomaterials, 34(12), pp.2875-2887, January 2013.

[2]        A.T. Metters, C.N. Bowman, K.S. Anseth, “A Statistical Kinetic Model for the Bulk Degradation of PLA-b-PEG-b-PLA Hydrogel Networks.” J. Phys. Chem. B, 104(30), pp.7043-7049, July 2000.