## 4 Hybrid Melt Electrospinning Writing-Fiber Reinforcement of Hydrogel Constructs
### Reinforcement Mechanism in Melt Electrowritten Fiber-Hydrogel Composites
The maximum tensile strain value that the composite could handle before irreversible deformation was recorded as being similar to the values of native soft tissues. After yielding point, manufactured fiber network elongated rather than being ruptured. Stiffness of the composite was several folds higher than the stiffness of hydrogel without reinforcement. Encapsulating human bone-marrow-derived mesenchymal precursor cells (hBMPCs) into the hydrogel assessed the biocompatibility of the soft network system. The encapsulated cells infiltrated into the curvy PCL MEW fibers were found to be viable after 72 h of incubation period. Cardiac tissue is another complex soft tissue with a highly organized fibrillar structure and mechanical strength. MEW manufacturing method offers great potential to establish an environment with a highly organized structure for cardiac tissue engineering by providing sufficient mechanical strength. Based on this idea, [PERSON] et al. systematically investigated the effect of hydrophobicity and the morphology of melt electrowritten PCL fibers on collagen reinforcement and the response of cardiac progenitor cells (CPCs) for potential therapeutic applications [84]. Due to the drawbacks of PCL, such as hydrophobic nature and slow degradation, hydroxyl-functionalized polyester, (poly (hydroxymethylglycolide-co-\(\varepsilon\)-caprolactone) (pHMGCL) was employed. Fiber scaffolds with rectangle and square geometries were manufactured while using two different formulations of polymers, which are PCL and pHMGCL-PCL blend. The fibrous scaffolds were evaluated with and without hydrogel forms. In case of fibrous networks without hydrogel, the tensile modulus of the blended-PCL scaffold was lower than that of scaffolds manufactured from PCL, but both types of scaffolds were in the similar range with the tensile modulus of human myocardium. However, those scaffolds showed different tensile modulus values that were based on their shapes. The rectangular shape exhibited anisotropic behavior of the native cardiac tissue. Even though tensile modulus and anisotropy of the scaffold showed almost similar mechanical characteristics to the native cardiac tissue, long-term mechanical features need to be investigated by employing cyclic tensile loading and other mechanical tests. In the case of composite structures, both blended and bare-PCL scaffold allowed collagen matrix infiltration in a uniform distribution, while collagen hydrogel with no support of PCL fiber scaffold remodeled into a clumped form. The analysis of CPCs in collagen hydrogel within both of the fiber scaffolds that were made up of PCL with and without blending with pHMGCL showed that the cells were 99% viable, regardless of the geometry and hydrophobicity of the fibers. However, cellular alignment and morphology changed, depending on geometry of the scaffold. Cells were randomly arranged in squared geometry scaffolds while the alignment of the cells was more regular, particularly in a preferential direction on rectangular ones. The number of aligned cells on the blended-PCL scaffold was found more than PCL scaffold, as shown in Figure 6. The nucleus of CPC's in the rectangular blended-PCL composites promoted less circular shape when compared to those in the square-shaped ones. In addition, it was observed that the interconnected porous structure also allowed the interaction of the cells between the compartments. This study revealed that hydrophobic nature of fibers and geometry of the scaffold strongly affect the interference between matrix and reinforcing fibers, which is reflected by cellular behavior. The authors also noted that pHMGCL might change the electrical stimulation on the fibers, which can also have a positive effect on CPC's response. A physiologically relevant 3D environment that was fabricated from melt electrowritten fibrous composite could be considered for treatment of myocardial regeneration. Generally, the treatment can be followed by replacement of the died cells during myocardial infarction with the healthy cells.