Controlled Biodegradation and Swelling of Strontium-doped Alginate/Collagen Scaffolds for Bone Tissue Engineering.

Treatment for critical size defects (CSDs) in bone often use bone grafts to act as a scaffold to help complete healing. Biological scaffolds require bone extraction from the individual or an outside donor while synthetic grafts mostly suffer from poor degradation kinetics and decreased bioactivity. In this study, we investigated a 3D printed scaffold derived from a novel composite bioink composed of alginate and collagen augmented with varying doses from 2 m g/ m L to 20 m g/ m L of 1% strontium-calcium polyphosphate (SCPP) to control biodegradability and fluid uptake. Scaffolds with increased SCPP concentrations showed higher particle density, lesser swelling ratio and greater biodegradability indicating that these critically important properties for bone healing are fine-tunable and highly dependent on SCPP dosing. Clinical Relevance- The dosing of 1% SCPP into porous alginate/collagen scaffolds provides adjustable long-term degradation and material properties suitable for potential in vivo CSD applications.

3D Printed Osteoblast-Alginate/Collagen Hydrogels Promote Survival, Proliferation and Mineralization at Low Doses of Strontium Calcium Polyphosphate.

The generation of biomaterials via 3D printing is an emerging biotechnology with novel methods that seeks to enhance bone regeneration. Alginate and collagen are two commonly used biomaterials for bone tissue engineering and have demonstrated biocompatibility. Strontium (Sr) and Calcium phosphate (CaP) are vital elements of bone and their incorporation in composite materials has shown promising results for skeletal repair. In this study, we investigated strontium calcium polyphosphate (SCPP) doped 3D printed alginate/collagen hydrogels loaded with MC3T3-E1 osteoblasts. These cell-laden scaffolds were crosslinked with different concentrations of 1% SCPP to evaluate the effect of strontium ions on cell behavior and the biomaterial properties of the scaffolds. Through scanning electron microscopy and Raman spectroscopy, we showed that the scaffolds had a granular surface topography with the banding pattern of alginate around 1100 cm-1 and of collagen around 1430 cm-1. Our results revealed that 2 mg/mL of SCPP induced the greatest scaffold degradation after 7 days and least amount of swelling after 24 h. Exposure of osteoblasts to SCPP induced severe cytotoxic effects after 1 mg/mL. pH analysis demonstrated acidity in the presence of SCPP at a pH between 2 and 4 at 0.1, 0.3, 0.5, and 1 mg/mL, which can be buffered with cell culture medium. However, when the SCPP was added to the scaffolds, the overall pH increased indicating intrinsic activity of the scaffold to buffer the SCPP. Moreover, cell viability was observed for up to 21 days in scaffolds with early mineralization at 0.3, 0.5, and 1 mg/mL of SCPP. Overall, low doses of SCPP proved to be a potential additive in biomaterial approaches for bone tissue engineering; however, the cytotoxic effects due to its pH must be monitored closely.

Bioprinting of Stem Cells in Multimaterial Scaffolds and Their Applications in Bone Tissue Engineering.

Bioprinting stem cells into three-dimensional (3D) scaffolds has emerged as a new avenue for regenerative medicine, bone tissue engineering, and biosensor manufacturing in recent years. Mesenchymal stem cells, such as adipose-derived and bone-marrow-derived stem cells, are capable of multipotent differentiation in a 3D culture. The use of different printing methods results in varying effects on the bioprinted stem cells with the appearance of no general adverse effects. Specifically, extrusion, inkjet, and laser-assisted bioprinting are three methods that impact stem cell viability, proliferation, and differentiation potential. Each printing method confers advantages and disadvantages that directly influence cellular behavior. Additionally, the acquisition of 3D bioprinters has become more prominent with innovative technology and affordability. With accessible technology, custom 3D bioprinters with capabilities to print high-performance bioinks are used for biosensor fabrication. Such 3D printed biosensors are used to control conductivity and electrical transmission in physiological environments. Once printed, the scaffolds containing the aforementioned stem cells have a significant impact on cellular behavior and differentiation. Natural polymer hydrogels and natural composites can impact osteogenic differentiation with some inducing chondrogenesis. Further studies have shown enhanced osteogenesis using cell-laden scaffolds in vivo. Furthermore, selective use of biomaterials can directly influence cell fate and the quantity of osteogenesis. This review evaluates the impact of extrusion, inkjet, and laser-assisted bioprinting on adipose-derived and bone-marrow-derived stem cells along with the effect of incorporating these stem cells into natural and composite biomaterials.