A Stand-alone Simulation Platform for Designing Tissue Engineering Scaffolds to Serve as Bone Graft Substitutes - Project Summary The high-value market for bone graft materials is a major stimulus for developing innovative and more effective products. This study can provide an attractive alternative to the commercially-available bone graft substitutes. We will develop a simulation platform for designing tissue engineering scaffolds to serve as bone graft substitutes. The Application Builder™ functionality in COMSOL® software will be used to develop a stand-alone user-friendly design tool freely accessible to students, educators, and researchers across the United States. No COMSOL® license will be required, and the application (app) will be available for Windows®, macOS®, and Linux®. This will enable non-domain specialists (e.g., scientists with limited expertise in modeling) to design 3D scaffolds with optimal composition and properties. We have shown that 3D-scaffolds can be optimized using COMSOL® to attain the biomechanical requirements and porosity constraints for bone tissue engineering (Biofabrication, 2017). The study outlined in this proposal will further optimize the scaffold architecture and composition by combining numerical optimization via COMSOL® (a finite-element modeling software), I-optimal design of experiments (DoE) via JMP® (a statistical design software), while eliminating the extrudate swell to generate design-driven architectures and enhance reproducibility. The JMP® functionality will be incorporated into the app as a user-defined model. We will design 3D-plotted composites made of slow-degrading and fast- degrading zones and optimize the design using COMSOL® and JMP®. The slow-degrading component of the hybrid scaffolds will be composed of poly(L-lactic acid) (PLLA) and nano-hydroxyapatite (nHA), whereas the fast- degrading component will be made of poly(lactic-co-glycolic acid)(PLGA), collagen (COL), and nHA. Micropores will be generated within the fast-degrading component upon the extraction of polyethylene glycol (PEG) porogen. The slow-degrading component will allow maintaining sufficient mechanical properties to support tissue growth after the erosion of the fast-degrading component. We anticipate that the fast-degrading zones will also overcome the transport limitations once implanted in vivo (future studies). A key requirement for bioengineered bone graft substitutes is the ability to provide the capacity for remodeling and rapid restoration of the biomechanical function. Our specific aims are: (Aim 1) Design non-hybrid and hybrid scaffolds with a modulus within the range of bone (COMSOL®), (Aim 2) Evaluate the in vitro cellular activity and optimize the scaffold composition (JMP®), and (Aim 3) Evaluate the optimized scaffold inside a bioreactor and develop/validate the COMSOL® app. We will validate the proposed simulation app using our hybrid 3D scaffolds. In Aim 3, four additional materials will also be tested for the validation of the app. The outcomes will be compared with the 3D scaffold designs reported in the scientific literature. We will showcase the software via LinkedIn, webinars, conferences, and Ohio Life Sciences Network. The software could also be used for cartilage tissue engineering. Adapting the software to osteochondral and vascular tissues engineering will be considered in our next studies.
