Application of 3D Bioprinting in Biomedical Engineering

Bioinks play a fundamental role in skin bioprinting, dictating the printing fidelity, cell response, and function of bioprinted 3D constructs. However, the range of bioinks that support skin cells’ function and aid in the bioprinting of 3D skin equivalents with tailorable properties and customized shapes is still limited. In this study, we describe a bioinspired design strategy for bioengineering double crosslinked pectin-based bioinks that recapitulate the mechanical properties and the presentation of cell-adhesive ligands and protease-sensitive domains of the dermal extracellular matrix, supporting the bioprinting of bilayer 3D skin models. Methacrylate-modified pectin was used as a base biomaterial enabling hydrogel formation via either chain-growth or step-growth photopolymerization and providing independent control over bioink rheology, as well as the mechanical and biochemical cues of cell environment. By tuning the concentrations of crosslinker and polymer in bioink formulation, dermal constructs were bioprinted with a physiologically relevant range of stiffnesses that resulted in strikingly site-specific differences in the morphology and spreading of dermal fibroblasts. We also demonstrated that the developed thiol-ene photo-clickable bioinks allow for the bioprinting of skin models of varying shapes that support dermis and epidermis reconstruction. Overall, the engineered bioinks expand the range of printable biomaterials for the extrusion bioprinting of 3D cell-laden hydrogels and provide a versatile platform to study the impact of material cues on cell fate, offering potential for in vitro skin modeling. Full article

Background: Scaffold (SCA) functionalization with aptamers (APT) provides adsorption of specific bioactive molecules on biomaterial surfaces. The aim of this study was to observe if SCA enriched with anti-fibronectin APT can favor coagulum (PhC) and osteoblasts (OSB) differentiation. Methods: 20 μg of APT was functionalized on SCA by simple adsorption. For PhC formation, SCAs were inserted into rat calvaria defects for 17 h. Following proper transportation (buffer solution PB), OSBs (UMR-106 lineage) were seeded over PhC + SCAs with and without APT. Cells and PhC morphology, PhC cell population, protein labeling and gene expression were observed in different time points. Results: The APT induced higher alkaline phosphatase and bone sialoprotein immunolabeling in OSB. Mesenchymal stem cells, leukocytes and lymphocytes cells were detected more in the APT group than when scaffolds were not functionalized. Additionally, an enriched and dense fibrin network and different cell types were observed, with more OSB and white blood cells in PhC formed on SCA with APT. The gene expression showed higher transforming growth factor beta 1 (TGF-b1) detection in SCA with APT. Conclusions: The SCA functionalization with fibronectin aptamers may alter key morphological and functional features of blood clot formation, and provides a selective expression of proteins related to osteo differentiation. Additionally, aptamers increase TGF-b1 gene expression, which is highly associated with improvements in regenerative therapies. Full article

In this work, we present a mathematical model of cell growth in the pores of a perfusion bioreactor through which a nutrient solution is pumped. We have developed a 2-D vertex model that allows us to reproduce the microscopic dynamics of the microenvironment of cells and describe the occupation of the pore space with cells. In this model, each cell is represented by a polygon; the number of vertices and shapes may change over time. The model includes mitotic cell division and intercalation. We study the impact of two factors on cell growth. On the one hand, we consider a channel of variable cross-section, which models a scaffold with a porosity gradient. On the other hand, a cluster of cells grows under the influence of a nutrient solution flow, which establishes a non-uniform distribution of shear stresses in the pore space. We present the results of numerical simulation of the tissue growth in a wavy channel. The model allows us to obtain complete microscopic information that includes the dynamics of intracellular pressure, the local elastic energy, and the characteristics of cell populations. As we showed, in a functional-graded scaffold, the distribution of the shear stresses in the pore space has a complicated structure, which implies the possibility of controlling the growth zones by varying the pore geometry. Full article

The cartilaginous nasal septum is integral to the overall structure of the nose. Developing our an-atomic understanding of the septum will improve the planning and techniques of septal surgeries. While the basic dimensions of the septum have previously been described, the average shape in the sagittal plane has yet to be established. Furthermore, determining the average shape allows for the creation of a mean three-dimensional (3D) septum model. To better understand the average septal shape, we dissected septums from 40 fresh human cadavers. Thickness was measured across pre-defined points on each specimen. Image processing in Photoshop was used to superimpose lateral photographs of the septums to determine the average shape. The average shape was then combined with thickness data to develop a 3D model. This model may be utilized in finite elemental analyses, creating theoretical results about septal properties that are more translatable to real-world clinical practice. Our 3D septum also has numerous applications for 3D printing. Realistic models can be created for educational or surgical planning purposes. In the future, our model could also serve as the basis for 3D-printed scaffolds to aid in tissue regeneration to reconstruct septal defects. The model can be viewed at the NIH 3D model repository (3DPX ID: 020598, Title: 3D Nasal Septum). Full article

Three-dimensional bioprinting is a promising technology for bone tissue engineering. However, most hydrogel bioinks lack the mechanical and post-printing fidelity properties suitable for such hard tissue regeneration. To overcome these weak properties, calcium phosphates can be employed in a bioink to compensate for the lack of certain characteristics. Further, the extracellular matrix of natural bone contains this mineral, resulting in its structural robustness. Thus, calcium phosphates are necessary components of bioink for bone tissue engineering. This review paper examines different recently explored calcium phosphates, as a component of potential bioinks, for the biological, mechanical and structural properties required of 3D bioprinted scaffolds, exploring their distinctive properties that render them favorable biomaterials for bone tissue engineering. The discussion encompasses recent applications and adaptations of 3D-printed scaffolds built with calcium phosphates, delving into the scientific reasons behind the prevalence of certain types of calcium phosphates over others. Additionally, this paper elucidates their interactions with polymer hydrogels for 3D bioprinting applications. Overall, the current status of calcium phosphate/hydrogel bioinks for 3D bioprinting in bone tissue engineering has been investigated. Full article

Background: Additive manufacturing (three-dimensional (3D) printing) has become a leading manufacturing technique in dentistry due to its various advantages. However, its potential applications for dental ceramics are still being explored. Zirconia, among ceramics, has increasing popularity and applications in dentistry mostly due to its excellent properties. Although subtractive manufacturing (3D milling) is considered the most advanced technology for the fabrication of zirconia restorations, certain disadvantages are associated with it. Methods: A systematic review was piloted to compare the clinical performance of zirconium crowns that were fabricated using three-dimensional (3D) milling and 3D printing. A meta-analysis was performed, and studies published up to November 2022 were identified. The terms searched were “Zirconium crowns”, “3D printing”, “CAD/CAM” (Computer-Aided Design and Computer-Aided Manufacturing), “Milling”, “dental crowns”, and “3D milling”. The characteristics that were compared were the year in which the study was published, study design, age of the patient, country, the number of crowns, the type of crown fabrication, marginal integrity, caries status, and outcomes. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to structure this systematic review. Out of eleven hundred and fifty titles identified after a primary search, nine articles were included in the quantitative analysis. The research question based on PICO/PECO (Participant, Intervention/exposure, Comparison, and Outcome) was “Do 3D-printed and milled (P) zirconia crowns and FDPs (I) have a better survival rate (O) when conventional prosthesis is also an option (C)”? The data collected were tabulated and compared, and the risk of bias and meta-analysis were later performed. Only nine articles (clinical research) were selected for the study. Since there were no clinical studies on the 3D printing of zirconium crowns, six in vitro studies were considered for the comparison. Zirconium crowns in the milling group had an average minimum follow-up of 6 months. Results: A moderate risk of bias was found, and survival was significant. A high heterogeneity level was noted among the studies. Marginal integrity, periodontal status, and survival rate were high. Linear regression depicted no statistical correlation between the type of cement used and the survival rate. Conclusions: It can be concluded that the milled crowns had a higher performance and satisfactory clinical survival. Full article