Fabrication and Analysis of Surface Functionalized Porous PCL-nHA Scaffolds With P(HEMA-co-EGDMA) Hydrogel via iCVD and BMP-2 Release Simulation
Authors: Aydin Mehmet Serhat , Bilgili Hatice Kubra , Sendur Gullu Kiziltas , Emanet Melis , Ince Gozde Ozaydin 
Published: February 2021

Abstract
Well-designed tissue engineering scaffolds are needed for effective healing by regulating cell behavior such as cell attachment, proliferation and differentiation. Scaffolds should not only exhibit biocompatibility, interconnected porosity and strength but should provide hydrophilic surface where cell adheres in-vitro and in-vivo. The aim of this study is the fabrication and analysis of porous and surface functionalized biocompatible scaffolds for bone tissue engineering. In the first part of the study, we produce porous polycaprolactone (PCL)-nano-hydroxyapatite (nHA) scaffolds using earlier proposed non-solvent induced phased separation (NIPS) and use initiated chemical vapor deposition (iCVD) for coating these scaffolds with Poly (hydroxyethylmethacrylate-co-ethyleneglycol dimethacrylate) (p(HEMA-co-EGDMA)) polymer. The goal is to increase hydrophilicity of scaffolds using iCVD coating on scaffolds fabricated using NIPS and to demonstrate its feasibility for further functionalization such as GF immobilization and release. In the second part of the paper we develop an initial analysis framework suitable for the characterization of BMP-2 growth factor (GF) release of both coated and uncoated bone scaffolds using a Finite Element Analysis taking into account diffusion and possible chemical reaction.
In the experimental part, surface characterization via Fourier-transform infrared spectroscopy (FTIR) confirmed a successful conformal coating and contact angle measurements demonstrate that desired hydrophilic surface was obtained after iCVD coating. Therefore, the first part of the study demonstrated that surface modified PCL-nHA scaffolds with p(HEMA-co-EGDMA) hydrogel exhibited increased hydrophilicity that should allow for augmented compatibility with cell media by enhancing cell attachment, proliferation and differentiation in vitro. In the computational part of the paper, as a second parametric study, the effects of a possible iCVD coating were analyzed by modifying the biomaterial matrix domain and tuning its diffusion coefficient where the reaction and release is expected to occur. The diffusion coefficient of coating material was set to two different values chosen lower than the tissue domain. Simulation results for the addition of a coating layer with a larger diffusion coefficient value resulted in a decreased BMP-2 diffusion accompanied by a parallel decrease in BMP-2 concentration in the tissue with respect to time and across the domain. Overall, it is concluded that initial parametric studies showed that the release and concentration profile could be tuned based on morphological and material properties of the scaffold. Also, coating biomaterial matrix via iCVD acquired directional/anisotropic diffusion in the model domain via one-sided coating of the scaffold matrix. Formal optimization studies could be integrated to the proposed simulation model to design functional scaffolds coated with iCVD for controlled and directional growth factor release.