Abstract
Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.
Highlights
Bone is one of the most transplanted tissues, with yearly around 2.2 million operations being performed worldwide [1]
By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones
We provide a novel strategy for bone tissue engineering in the context of large bone defects and demonstrate the feasibility of bioprinting constructs with computationally designed spatial patterns of cells
Summary
Bone is one of the most transplanted tissues, with yearly around 2.2 million operations being performed worldwide [1]. Distraction osteogenesis, a bone lengthening procedure, provides a surgical alternative but requires long healing times [3, 4]. Tissue engineering, combining cells with growth factor technology and a biomaterial carrier (scaffold) into living constructs that promote tissue regeneration, is a promising alternative [5]. Difficulties in healing bone defects persist mainly due to the heterogeneous and often insufficient nutrient and oxygen supply at the site of transplantation leading to cell death and incomplete regeneration/healing [6]. Given the spatial heterogeneity of the healing process, we hypothesize that the tissue engineering construct design must consider spatially heterogeneous (i.e., patterned) initial distributions of biological factors. We propose that a well-designed tissue engineering construct, with an optimized spatial pattern of cell densities in a material matrix, will improve fracture healing in large segmental defects
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