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Powder-based inkjet 3D printing method is one of the most attractive solid free form techniques. It involves a sequential layering process through which 3D porous scaffolds can be directly produced from computer-generated models. 3D printed products' quality are controlled by the optimal build parameters. In this study, Calcium Sulfate based powders were used for porous scaffolds fabrication. The printed scaffolds of 0.8 mm pore size, with different layer thickness and printing orientation, were subjected to the depowdering step. The effects of four layer thicknesses and printing orientations, (parallel to X, Y and Z), on the physical and mechanical properties of printed scaffolds were investigated. It was observed that the compressive strength, toughness and Young's modulus of samples with 0.1125 and 0.125 mm layer thickness were more than others. Furthermore, the results of SEM and μCT analyses showed that samples with 0.1125 mm layer thickness printed in X direction have more dimensional accuracy and significantly close to CAD software based designs with predefined pore size, porosity and pore interconnectivity.

While spinal interbody cage options have proliferated in the past decade, relatively little work has been done to explore the comparative potential of biomaterial technologies in promoting stable fusion. Innovations such as micro-etching and nano-architectural designs have shown purported benefits in in vitro studies, but lack clinical data describing their optimal implementation. Here, we critically assess the pre-clinical data supportive of various commercially available interbody cage biomaterial, topographical, and structural designs. We describe in detail the osteointegrative and osteoconductive benefits conferred by these modifications with a focus on polyetheretherketone (PEEK) and titanium (Ti) interbody implants. Further, we describe the rationale and design for two randomized controlled trials, which aim to address the paucity of clinical data available by comparing interbody fusion outcomes between either PEEK or activated Ti lumbar interbody cages. Utilizing dual-energy computed tomography (DECT), these studies will evaluate the relative implant-bone integration and fusion rates achieved by either micro-etched Ti or standard PEEK interbody devices. Taken together, greater understanding of the relative osseointegration profile at the implant–bone interface of cages with distinct topographies will be crucial in guiding the rational design of further studies and innovations.

Collagen fibrils serve as the major template for mineral deposits in both biologically derived and engineered tissues. In recent years certain non-collagenous proteins have been elucidated as important players in differentially modulating intra vs. extra-fibrillar mineralization of collagen. We and others have previously shown that the expression of the collagen receptors, discoidin domain receptors (DDR1 and DDR2) positively correlate with mineralization of the extra-cellular matrix (ECM). While the role of DDR-mediated cell-signaling in modulating ECM mineralization is an active area of research, very little is understood on how DDRs influence the location, type and quality of mineral deposits in the ECM. This study employs a biomimetic approach to take a closer look at naturally derived ECM and its mineralization by DDRs. The first chapter provides a brief overview of the components of the extracellular matrix (ECM) and their role in modulating mineralization. We also summarize our current understanding of DDRs in modulating ECM mineralization. The first aim of this thesis (Chapter 2) was to examine if the ectodomain (ECD) of DDR2 modulates intra versus extra-fibrillar mineralization of collagen independent of cell-signaling. For this purpose, a decellularized collagenous substrate, namely glutaraldehyde fixed porcine pericardium (GFPP) was subjected to biomimetic mineralization protocols. GFPP was incubated in modified simulated body fluid (mSBF) or polymer-induced liquid precursor (PILP) solutions in the presence of recombinant DDR2 ECD (DDR2-Fc) to mediate extra or intra- fibrillar mineralization of collagen. Thermogravimetric analysis revealed that DDR2-Fc increased mineral content in GFPP calcified in mSBF while no significant differences were observed in PILP mediated mineralization. Electron microscopy approaches were used to evaluate the quality and quantity mineral deposits. An increase in the matrix to mineral ratio, frequency of particles and size of mineral deposits, was observed in the presence of DDR2-Fc in mSBF. The EDS map and spectra of mineralized collagen confirmed the presence of calcium phosphate and DDR2 ECD did not change the composition. However, Raman spectra and electron diffraction pattern of calcium phosphates confirmed the deposition of crystalline hydroxyapatite in the presence of DDR2 ECD. The second aim of this thesis (Chapter 3) was to investigate the interaction of DDR2 ECD with collagen and the mineral phase and its influence on mineralization. Von Kossa staining and The third aim of this thesis (Chapter 4) was to study the effect of genetically modified ECM on matrix mineralization. For this purpose, de-cellularized aortic tissue derived from DDR1 knock-out (KO) mice and wildtype littermate were subjected to the biomimetic mineralization protocols. Matrix mineralization of the resulting tissue was analyzed using histochemical stains and electron microscopy. Von kossa staining indicated that tissues from wildtype mice exhibited enhanced mineral deposition when incubated in mSBF and PILP as compared to DDR1 KO. A major site of mineralization was the elastin lamella present in the medial layer of the aorta. Ultrastructural analysis of collagen fibrils revealed that extrafibrillar mineralization was enhanced in fibrils from the wild-type mice. Endogenous mineralization of aortic valves was attenuated in DDR1 KO mice consistent with our results using biomimetic protocols. Finally, in chapter 5, we summarize the role of DDRs at the cell-matrix interface in modulating the location, type and quality of ECM mineralization and its implications in health and disease.immunohistochemistry analysis of adjacent sections indicated that recombinant DDR2-Fc bound to both the matrix and the mineral phase of GFPP subjected to biomimetic protocols. Further, DDR2-Fc was found to bind to hydroxyapatite (HAP) particles and enhance the nucleation of mineral deposits in mSBF solutions independent of collagen. Taken together, our observations elucidate DDR2 ECD as a novel player in the modulation of extra-fibrillar mineralization of collagen by binding to native collagen, binding to HAP and promoting nucleation of HAP.

Powder-based inkjet 3D printing method is one of the most attractive solid free form techniques. It involves a sequential layering process through which 3D porous scaffolds can be directly produced from computer-generated models. 3D printed products' quality are controlled by the optimal build parameters. In this study, Calcium Sulfate based powders were used for porous scaffolds fabrication. The printed scaffolds of 0.8 mm pore size, with different layer thickness and printing orientation, were subjected to the depowdering step. The effects of four layer thicknesses and printing orientations, (parallel to X, Y and Z), on the physical and mechanical properties of printed scaffolds were investigated. It was observed that the compressive strength, toughness and Young's modulus of samples with 0.1125 and 0.125 mm layer thickness were more than others. Furthermore, the results of SEM and mu CT analyses showed that samples with 0.1125 mm layer thickness printed in X direction have more dimensional accuracy and significantly close to CAD software based designs with predefined pore size, porosity and pore interconnectivity.