A 3D bioprinting system to produce human-scale tissue constructs with structural integrity

Abstract

A challenge for tissue engineering is producing three-dimensional (3D), vascularized cellular constructs of clinically relevant size, shape and structural integrity. We present an integrated tissue-organ printer (ITOP) that can fabricate stable, human-scale tissue constructs of any shape. Mechanical stability is achieved by printing cell-laden hydrogels together with biodegradable polymers in integrated patterns and anchored on sacrificial hydrogels. The correct shape of the tissue construct is achieved by representing clinical imaging data as a computer model of the anatomical defect and translating the model into a program that controls the motions of the printer nozzles, which dispense cells to discrete locations. The incorporation of microchannels into the tissue constructs facilitates diffusion of nutrients to printed cells, thereby overcoming the diffusion limit of 100-200 μm for cell survival in engineered tissues. We demonstrate capabilities of the ITOP by fabricating mandible and calvarial bone, cartilage and skeletal muscle. Future development of the ITOP is being directed to the production of tissues for human applications and to the building of more complex tissues and solid organs.

Impression 3D en médecine régénératrice et ingénierie tissulaire

“…Plus récemment, nous avons pu imprimer du collagène, de l'hydroxyapatite et des cellules souches mésenchymateuses et nous avons observé que le motif cellulaire imprimé pouvait guider la cicatrisation (Figure 4 [34]. Ils ont ainsi pu démontrer, par des techniques combinées, intégrées dans une seule bio-imprimante, qu'il était possible de reconstruire : (1) une portion de mandibule de morphologie adaptée à la perte de substance (3,6 × 3, 2 × 1,6 cm), et la fabrication d'un os de calvaria 3 qui permet la régénération osseuse chez le rat ; (2) un muscle strié squelettique (15 × 1 × 5 mm) innervé et répondant à des stimulations électriques après implantation in vivo chez le rat ; (3) le cartilage de l'oreille (3,2 × 0,9 × 1,6 cm), qui présente une forme complexe, qui a été maintenue deux mois après implantation pour maturation en site sous-cutané chez des rats athymiques [34]. La bio-impression in situ consiste à bio-imprimer des cellules, de la matrice, des facteurs de croissance directement au niveau de la perte tissulaire pour favoriser la régénération du tissu lésé.…”

Progress in scaffold‐free bioprinting for cardiovascular medicine

“…Here, we will leave out multiple applications of 3D printing (with no cells involved) to cardiovascular field, as well as the scaffold‐only printing,5 and the “hybrid” forms of bioprinting,6 which have been discussed in other excellent reviews recently 3. Instead, we will highlight scaffold‐free bioprinting as bona fide biofabrication, here understood as the creation of living, functional 3D constructs with cardiovascular applications.…”

Advances in bioprinted cell-laden hydrogels for skin tissue engineering

“…Contrary to bioassembly, where the minimum fabrication units are pre-formed cell building blocks, bioprinting makes use of fabrication units down to molecular level [78]. Bioprinting processes are capable of printing living and non-living materials in a computercontrolled and automated manner with high levels of resolution, accuracy and reproducibility, enabling the generation of biological substitutes with intricate architectures, precise geometrical configurations and biomechanical heterogeneity [16,80,91,92]. Bioprinting technologies can be classified in three main categories: inkjet bioprinting, laser-assisted bioprinting and extrusion bioprinting (Table 1) [111,125,191].…”

“…Bioprinting, one main strategy of biofabrication, is attracting significant interest from researchers working in the field of tissue engineering and regenerative medicine due to their unique ability to print single cells, bioactive molecules, biomaterials or cell-aggregates into structurally organized constructs in a layer-by-layer fashion with high resolution and accuracy [10,78,111,136]. Bioprinting provides a powerful tool to arrange cells, biomaterials and soluble factors within a 3D environment on a length scale comparable to the complex heterogeneity found in natural tissue (10-100 lm), enabling new perspectives as well as unmatched possibilities in the design of biomimetic substitutes for tissue regeneration [10,80,125]. In the context of skin tissue engineering, bioprinting has been explored for the fabrication of 3D constructs containing skin cells positioned in distinct layers to resemble the anatomy of native skin [117,184].…”