Three-dimensional (3D) pigmented human skin constructs have been fabricated using a 3D bioprinting approach. The 3D pigmented human skin constructs are obtained from using three different types of skin cells (keratinocytes, melanocytes and fibroblasts from three different skin donors) and they exhibit similar constitutive pigmentation (pale pigmentation) as the skin donors. A two-step drop-on-demand bioprinting strategy facilitates the deposition of cell droplets to emulate the epidermal melanin units (pre-defined patterning of keratinocytes and melanocytes at the desired positions) and manipulation of the microenvironment to fabricate 3D biomimetic hierarchical porous structures found in native skin tissue. The 3D bioprinted pigmented skin constructs are compared to the pigmented skin constructs fabricated by conventional a manual-casting approach; in-depth characterization of both the 3D pigmented skin constructs has indicated that the 3D bioprinted skin constructs have a higher degree of resemblance to native skin tissue in term of the presence of well-developed stratified epidermal layers and the presence of a continuous layer of basement membrane proteins as compared to the manually-cast samples. The 3D bioprinting approach facilitates the development of 3D in vitro pigmented human skin constructs for potential toxicology testing and fundamental cell biology research.
Bioprinting is an emerging research field that has attracted tremendous attention for various applications; it offers a highly automated, advanced manufacturing platform for the fabrication of complex bioengineered constructs. Different bio-inks comprising multiple types of printable biomaterials and cells are utilized during the bioprinting process to improve the homology to native tissues and/or organs in a highly reproducible manner. This paper, presenting a first-time comprehensive yet succinct review of microvalve-based bioprinting, provides an in-depth analysis and comparison of different drop-on-demand bioprinting systems and highlights the important considerations for microvalve-based bioprinting systems. This review paper reports a detailed analysis of its printing process, bio-ink properties and cellular components on the printing outcomes. Lastly, this review highlights the significance of drop-on-demand bioprinting for various applications such as high-throughput screening, fundamental cell biology research, in situ bioprinting and fabrication of in vitro tissue constructs and also presents future directions to transform the microvalve-based bioprinting technology into imperative tools for tissue engineering and regenerative medicine.
Bioprinting is a promising automated platform that enables the simultaneous deposition of multiple types of cells and biomaterials to fabricate complex three-dimensional (3D) tissue constructs. Collagen-based biomaterial used in most of the previous works on skin bioprinting has poor printability and long crosslinking time. This posed an immense challenge to create 3D constructs with pre-determined shape and configuration at high throughput. Recently, the use of chitosan for wound healing applications has attracted huge attention due to its attractive traits such as its antimicrobial properties and ability to trigger hemostasis. In this paper, we optimized polyelectrolyte gelatin-chitosan hydrogel for 3D bioprinting. Modification to the chitosan was carried out via the oppositely charged functional groups from chitosan and gelatin at a specific pH of ~pH 6.5 to form polyelectrolyte complexes. The polyelectrolyte hydrogels were evaluated in terms of physical interactions within polymer blend, rheological properties (viscosities, storage and loss modulus), printing resolution at varying pressures and feed rates and biocompatibility. The polyelectrolyte gelatin-chitosan hydrogels formulated in this work was optimized for 3D bioprinting at room temperature to achieve high shape fidelity of the printed 3D constructs and good biocompatibility with fibroblast skin cells.
The ability to have precise control over porosity, scaffold shape, and internal pore architecture is critical in tissue engineering. For anchorage-dependent cells, the presence of three-dimensional scaffolds with interconnected pore networks is crucial to aid in the proliferation and reorganization of cells. This research explored the potential of rapid prototyping techniques such as selective laser sintering to fabricate solvent-free porous composite polymeric scaffolds comprising of different blends of poly(ether-ether-ketone) (PEEK) and hydroxyapatite (HA). The architecture of the scaffolds was created with a scaffold library of cellular units and a corresponding algorithm to generate the structure. Test specimens were produced and characterized by varying the weight percentage, starting with 10 wt% HA to 40 wt% HA, of physically mixed PEEK-HA powder blends. Characterization analyses including porosity, microstructure, composition of the scaffolds, bioactivity, and in vitro cell viability of the scaffolds were conducted. The results obtained showed a promising approach in fabricating scaffolds which can produce controlled microarchitecture and higher consistency.
The dawn of commercial bioprinting is rapidly advancing the tissue engineering field. In the past few years, new bioprinting approaches as well as novel bioinks formulations have emerged, enabling biological research groups to demonstrate the use of such technology to fabricate functional and relevant tissue models. In recent years, several companies have launched bioprinters pushing for early adoption and democratisation of bioprinting. This article reviews the progress in commercial bioprinting since the inception, with a particular focus on the comparison of different available printing technologies and important features of the individual technologies as well as various existing applications. Various challenges and potential design considerations for next generations of bioprinters are also discussed.
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