A potential solution for prosthetic heart valves is tissue-engineered heart valves. Tissue-engineered heart valves (TEHVs) are designed to replicate the complex properties found in natural tissues, such as stiffness, anisotropy, and composition and organization of cells and extracellular matrix (ECM). Electrospinning is regarded as a highly versatile and innovative approach for fabricating numerous fibrous designs. In this review, we discuss recent developments in electrospun heart valve scaffolds, including scaffold materials, cell types, and electrospinning setups used to prepare aligned nanofibers. Despite the fact that natural biomaterials provided excellent biocompatibility, nanofibers from synthetic materials provided the required mechanical compatibility. Accordingly, most studies highlighted the benefits of designing composite heart valves using biological and synthetic polymers. Various strategies, such as the application of motorized mandrel and micropatterned collector in electrospinning were effective in controlling nanofiber alignment. Studies also showed that aligned nanofiber’s mechanical strength and anisotropic structure promote cell proliferation, and differentiation, and promote attachment. Numerous studies have reported that multiple cell sources are suitable for producing heart valves. Successful results were obtained with human umbilical vein endothelial cells (HUVECs), since they provide a convenient cell source for cellularization of valve leaflets. A higher conductivity of scaffolds was achieved by using biomaterials that conduct electricity, such as polyaniline, polypyrrole, and carbon nanotubes, which resulted in better differentiation of precursor cells to cardiomyocytes and higher cell beating rates. In light of these attributes, nanofibrous scaffolds produced through electrospinning are expected to offer numerous advantages for tissue engineering and medical applications in the near future. However, multiple challenges were identified as cell infiltration and 2D nature of nanofiber mats necessitate further engineering approaches in electrospinning procedure leaflet production.

The design of effective treatments for critical size bone defects, which result from various conditions such as trauma, infection, injury, or tumor resection, presents a significant challenge in clinical practice. While autologous grafts are commonly regarded as gold standard treatments in these complex healing scenarios, they are often associated with notable limitations, including donor site morbidity and limited graft volume. As a result, recent research trends have shifted towards developing biomaterials that better emulate the inherent complexity of the native bone structure and function through implementation of a “Diamond Concept” polytherapy strategy. Central to this approach is the utilization of biomaterials, increasingly composed of composite materials that integrate bioactive osteoinductive factors and cell sources to enhance healing outcomes. The usage of Wnt signaling specific agonists as osteoinductive mediators has been recently shown to be a promising strategy for promoting healing, as this pathway is well established to have an important role in both osteogenic differentiation and bone formation processes. Implementation of a localized delivery system through scaffold incorporation is necessary in this scenario, however, to minimize any potential off-target effects caused by the Wnt signaling cascade’s non-specificity to bone. Findings in the literature clearly show that this approach holds promise to improve clinical healing outcomes, paving the way for more effective treatment options. In this review, we will generally discuss the design of biomaterials, specifically bulk materials and composites, for the treatment of critical size bone defects. Additionally, we will highlight recent work on the design of chitosan-based scaffolds modified with purine crosslinking, to overcome cytotoxicity issues associated with other chemical crosslinkers. In this context, we focus on optimizing material design for this bone healing application and discuss the benefits of localized Wnt agonist as mediators to improve the scaffold’s osteoinductive behavior.