Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering

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.

Development of Bioink from Decellularized Tendon Extracellular Matrix for 3D Bioprinting

“…The development of biomaterials for bioprinting processes has become one of the major objectives of tissue engineering in recent years . Hydrogel materials are frequently used in bioprinting either as support structures for providing shape fidelity to printed cell aggregates or cell‐encapsulating matrices for delivery of cells to predetermined shapes . For both cases, hydrogel materials should provide certain properties such as printability, mechanical stability, biocompatibility, and biomimicry for effective bioprinting process and long term biological activity of the bioprinted constructs.…”

A hybrid additive manufacturing platform to create bulk and surface composition gradients on scaffolds for tissue regeneration

“…Plasma polymerization offers a plethora of features that are unachievable by other existing techniques applied to TE scaffolds. For example, it can be used to leave selected areas untreated and hence non-celladhesive, offering a way to guide cell distribution on scaffolds in order to improve tissue regeneration (17). Plasma treatment patterning could also be used to achieve islands of different cell populations, which can be useful for TE strategies requiring multiple cell types.…”

Modeling, simulations, and optimization of smooth muscle cell tissue engineering for the production of vascular grafts

“…The vast number of computational simulation studies in the literature, including recent ones, are dedicated to cartilage (Bandeiras & Completo, 2017;Y. Zhu et al, 2017) and bone tissue engineering (Bersini et al, 2016;Carlier et al, 2016;Guyot et al, 2014;Song et al, 2013;Song et al, 2015;Spencer, Hidalgo-Bastida, Cartmell, Halliday, & Care, 2013;Zhao, Vaughan, & Mcnamara, 2015). To the best of our knowledge, no such modeling and computational simulation studies have been published for vascular tissue engineering despite a plethora of experimental studies in the literature, and as such the present paper breaks new ground.…”

“…Hence, the focus in this study is on a continuum transport model in a multiphase medium to represent a porous scaffold, with an additional growing cell phase and a permeating culture medium, where phase volume averaging has been applied (Gosman, Lekakou, Politis, Issa, & Looney, ; Lemon & King, ). The vast number of computational simulation studies in the literature, including recent ones, are dedicated to cartilage (Bandeiras & Completo, ; Y. Zhu et al, ) and bone tissue engineering (Bersini et al, ; Carlier et al, ; Guyot et al, ; Song et al, ; Song et al, ; Spencer, Hidalgo‐Bastida, Cartmell, Halliday, & Care, ; Zhao, Vaughan, & Mcnamara, ). To the best of our knowledge, no such modeling and computational simulation studies have been published for vascular tissue engineering despite a plethora of experimental studies in the literature, and as such the present paper breaks new ground.…”