Fabrication of 3D Bone Scaffolds Functionalized With Spatiotemporal Release of BMP-2 Growth Factor via iCVD to Enhance Osteoregeneration
Authors: Bilgili Hatice Kubra , Ozaydin Ince Gozde , Emanet Melis , Kiziltas Sendur Gullu 
Published: February 2021

Abstract
3D scaffolds are known to be used in bone tissue engineering applications due to their great potential of providing multi-functionalized environment for cells. Different production techniques have been used focusing on changing geometrical features or adding biological/chemical compounds to improve the functionality of current 2D/3D scaffolds. A critical component to this functionalization relates to the effect of endogenous and exogeneous growth factors (GF) in the bone regeneration process that could be incorporated to the scaffolds via Initiated Chemical Vapor Deposition (iCVD) which is a solvent free method that requires low energy while also containing a wide variety of monomer choices for the layer by layer coating of polymers with individual functionality choices. However, GFs come with several difficulties such as rapid deactivation, low protein stability profile and little time of half-life, hence ideal environments that can overcome these issues are yet to be defined. Towards that goal, in this study we develop a computational framework based on the implementation of the advection-diffusion-reaction Partial Differential Equations (PDE) in a Finite Element Analysis (FEA) solver in COMSOL Multiphysics software. The goal is to develop a tool and conduct an initial analysis to be utilized for the simulation of multi-layer scaffold functionalized using encapsulation and immobilization of GFs inside nanoparticles possibly via iCVD. In this paper we focus on the analysis of two typical GF (BMP-2 and TGF) release mechanisms based on the effect of key material and geometrical parameters such as thickness of layers, initial GF concentration, diffusion coefficient, release function and uptake rate (absorption coefficient). The ultimate goal is to develop a model that can be used for future bone scaffold design studies when integrated to more advanced optimization methodologies. This model with further integration and updates of chemical and biological parameter measurements and inclusion of presence of antibodies should lay down a valuable basis for directing possible experimental functionalization efforts and their effects on the healing process of bone tissue. Initial results indicate that the proposed computational model can be utilized to predict the response of multi-layered bone scaffolds in terms of the concentration profiles of the GFs. Results of the parametric study presented in this paper prompt for the relative importance of each parameter in tuning the GF release profiles and point towards the need for formal optimization studies to achieve desired GF release responses considering all factors simultaneously. Among them, the diffusion coefficient is a key parameter with both a dominant effect on the GF profile and its ability to characterize different coatings using iCVD methods. As a next step, the developed framework will be updated to incorporate more detailed surface reactions and morphological data to simulate iCVD coated growth factors and verified with possible in-vitro studies before its integration to a formal optimization methodology.