Skin in vitro models offer much promise for research, testing drugs, cosmetics, and medical devices, reducing animal testing and extensive clinical trials. There are several in vitro approaches to mimicking human skin behavior, ranging from simple cell monolayer to complex organotypic and bioengineered 3-dimensional models. Some have been approved for preclinical studies in cosmetics, pharmaceuticals, and chemicals. However, development of physiologically reliable in vitro human skin models remains in its infancy. This review reports on advances in in vitro complex skin models to study skin homeostasis, aging, and skin disease.

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.

3D bioprinting is a powerful enabling technology for the automated fabrication of biomimetic constructs for skin modelling and repair with high resolution and reproducibility. Bioinks, which often ...

Pelvic organ prolapse (POP) is a health condition that can significantly impact patients’ quality of life. Unfortunately, most available treatments present drawbacks such as high recurrence rates, risk of complications, poor tissue integration, and the need for reintervention. One promising alternative is the use of biodegradable implantable meshes, which can support the organs, guide tissue regeneration, and be fully absorbed without damaging the surrounding tissues. In this study, biodegradable polycaprolactone (PCL) meshes were fabricated using melt electrowritten (MEW), incorporating the antistatic agent Hostastat^® FA 38 (HT) to address these limitations. The goal was to produce microscaffolds with suitable biophysical properties, particularly more stable fiber deposition and reduced fiber diameter. Different HT concentrations (0.03, 0.06, and 0.1 wt%) were investigated to assess their influence on the fiber diameter and mechanical properties of the PCL meshes. Increasing HT concentration significantly reduced fiber diameter by 14–17%, 39–45%, and 65–66%, depending on mesh geometry (square or sinusoidal). At 0.06 wt%, PCL/HT meshes showed a 24.10% increase in tensile strength and a 55.59% increase in Young’s Modulus compared to pure PCL meshes of similar diameter. All formulations demonstrated cell viability >90%. Differential scanning calorimetry (DSC) revealed preserved thermal stability and changes in crystallinity with HT addition. These findings indicate that the antistatic agent yields promising results, enabling the production of thinner, more stable fibers with higher tensile strength and Young’s Modulus than PCL meshes, without adding cellular toxicity. Developing a thinner and more stable mesh that mimics vaginal tissue mechanics could offer an innovative solution for POP repair.

Three-dimensional (3D) bioprinting technologies enable the automated fabrication of tissue constructs through the spatially controlled deposition of cells, biomaterials and/or bioactive molecules. Technological developments of bioprinting and the design of bioinspired biomaterials allow the biofabrication of a set of biologically relevant 3D tissue constructs to aid tissue repair and serve as biomimetic in vitro models for therapeutic screening. Bioprinted in vitro 3D models have been successfully established and employed to investigate patient-specific responses to drugs and therapies, while pre-clinical studies have shown the ability of bioprinted 3D constructs in promoting tissue repair. However, further studies are required to assess and validate the predictive value of tissue models and the functional properties of repaired tissues. In this chapter, we provide an overview of bioprinting strategies used to create bioengineered tissue constructs, focusing on their application as implantable grafts for tissue repair and in vitro models for tissue modelling and therapeutic screening.