Emulating Human Tissues and Organs: A Bioprinting Perspective Toward Personalized Medicine

Abstract

The lack of in vitro tissue and organ models capable of mimicking human physiology severely hinders the development and clinical translation of therapies and drugs with higher in vivo efficacy. Bioprinting allow us to fill this gap and generate 3D tissue analogues with complex functional and structural organization through the precise spatial positioning of multiple materials and cells. In this review, we report the latest developments in terms of bioprinting technologies for the manufacturing of cellular constructs with particular emphasis on material extrusion, jetting, and vat photopolymerization. We then describe the different base polymers employed in the formulation of bioinks for bioprinting and examine the strategies used to tailor their properties according to both processability and tissue maturation requirements. By relating function to organization in human development, we examine the potential of pluripotent stem cells in the context of bioprinting toward a new generation of tissue models for personalized medicine. We also highlight the most relevant attempts to engineer artificial models for the study of human organogenesis, disease, and drug screening. Finally, we discuss the most pressing challenges, opportunities, and future prospects in the field of bioprinting for tissue engineering (TE) and regenerative medicine (RM).

Controlling Structure with Injectable Biomaterials to Better Mimic Tissue Heterogeneity and Anisotropy

“…For more information on this topic, we refer the reader to recently published review papers about bioinks. [139][140][141][142] The lack of suitable bioinks is, therefore, currently one of the biggest bottlenecks for in vivo bioprinting. Combining the structural building blocks mentioned above with emerging in vivo bioprinting techniques opens many new opportunities to achieve hierarchical structures down to the nano-to micron-scale.…”

Current Insights into 3D Bioprinting: An Advanced Approach for Eye Tissue Regeneration

“…The bio-ink is composed of structural components or biomaterials, crosslinkers, functional elements and living cells. Compared to non-biological printing, which has been proved suitable for the manufacturing of medical devices and patient-tailored prosthetics for more than 30 years [8], 3D bioprinting involves additional challenges and requires the multidisciplinary integration of different technological and medical fields. These complexities refer mainly to the selection of biocompatible materials, cell types, biomechanical cues and the overcoming of technical difficulties due to the sensitivities of living cells [9].…”

“…In this case, the composition of biological inks raises some concerns, not only associated with the security of the grafts implanted, but also related to the biological origin of such cells [3]. In the clearest scenario, where patient's autologous cells are included in the bio-ink composition, a random migration of cells from implanted ocular grafts could arise in different parts of the body, leading to potential undesired effects [5,8]. It is also likely that the biological behavior of such cells can be altered due to the mechanical stress that cells suffer by the transient forces applied during the bioprinting process.…”

Towards Modelling Genetic Kidney Diseases with Human Pluripotent Stem Cells

“…These conditions, however, do not fully mimic the shear stresses from a high pressure renal arterial supply found in native kidneys, nor the delivery of blood cells, oxygen, nutrients, and bioactive molecules occurring in vivo. Achieving the normal vessel blood flow in these systems will be challenging and future approaches may make use of bioprinting strategies for engineering a perfusable vasculature within in vitro organoids [54, 55]. Such strategies may enable fuller functionality, especially active glomerular filtration, and will be needed to model later pathology found in diseased kidneys.…”