## 4 Hybrid Melt Electrospinning Writing-Fiber Reinforcement of Hydrogel Constructs
### Reinforcement Mechanism in Melt Electrowritten Fiber-Hydrogel Composites
Since induced-pluripot stem cells (iPSCs) have the capability of generating large numbers of human cardiomyocytes, they are the target for direct transplantation, which showed promising results in non-human primates. However, they are not effective due to limited contractility and electrical instability. Complex fibrillar architecture and mechanical characteristics of myocardial tissue were intended to be recapitulated for the production of heart patch in another study of [PERSON] et al. [118]. For this purpose, fiber networks with the hexagonal and rectangular structure were manufactured via MEW and then seeded with human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM), which was encapsulated within a collagen-based hydrogel matrix. Under in-plane tensile loading conditions, biaxial deformation characteristic of the hexagonal fiber scaffold was found to be superior to the rectangular-shaped scaffold. Although the results were better than the rectangular fiber scaffold, deformation, and fatigue behavior of the hexagonal fiber network was poor in the y-direction. The fatigue behavior of the hexagonal fiber scaffold after cyclic tensile loading was more promising than the one in the case of the rectangular fiber network. IPSCs encapsulated in a collagen-based hydrogel were used to monitor the effect of different geometrical composite structures on cellular behavior. The cells were aligned through the fibers and they showed synchronous contractions throughout the scaffold. The cells in the hexagonal fiber network showed faster contractions and maturation of contractile myocytes. In vivo studies followed by injection of the matureted cardiac patch onto a beating, the porcine heart did not reveal harmful effects on cell viability and on integrity of the engineered construct. It was proposed that fabrication of PCL fiber network with hexagonal microstructure improved the biaxial deformation and compliance. Another different biomimetic design and fabrication strategy was proposed for heart valve tissue engineering (HVTE) in the study carried out by [PERSON] et al. [116]. The biomechanical characteristics of heart valve leaflets were aimed to be achieved by highly organized wavy-like PCL melt electrowritten fiber scaffold to mimic the collagen fibers that are present in the structure of the heart valve. Human vascular smooth muscle cells (HUVSMCs) were seeded to the scaffold either directly onto the scaffold  
Figure 6: **(A) Viability and (B) morphology of cardiac progenitor cells (CPCs) in collagen hydrogel infiltrated in squared and rectangular bare-PCL and blended-PCL scaffolds [84] Copyright 2017 by Wiley-VCH Verlag GmbH & Co. KGaA Weinheim. Reprinted by permission of John Wiley and Sons. **  
or by encapsulating in fibrin hydrogel, followed by casting to the scaffold. The mechanical features of the manufactured construct showed similar results with native tissue in terms of J-shaped stress-strain curve behavior, anisotropy, and viscoelasticity. HUVSMC in the homogenously formed composite sustained the viability and exhibited the biochemical and mechanical properties of the main ECM component of native heart valve leaflet with the enhanced synthesis of collagen type I and type III. In the aforementioned studies on cardiac tissue engineering, uniaxial tensile tests were only performed on the fiber scaffolds without hydrogel matrix. Although it would be speculated that the main contributor to the mechanical properties of the composite is fiber network, investigation of the fiber network with hydrogel matrix due to the synergistic effect of the hybrid structure would reveal valuable understanding. There are other reports that consist of melt electrowritten fibers and hydrogel composites. In those studies, although their potential to recapitulate tissue functions was reported, their mechanical properties were not explored. For example, [PERSON] et al. presented an approach for periosteum regeneration [PERSON] et al. (2018).