Electrospinning (ES) techniques produce fibrous scaffolds that closely mimic the three‐dimensional architecture of the extracellular matrix (ECM), providing a favorable microenvironment for cell proliferation, migration, differentiation, and function within a supportive framework. Replicating this native structure with nontoxic materials is essential for tissue regeneration (RG). Polyhydroxyalkanoates (PHAs), particularly polyhydroxybutyrate (PHB), are a class of natural polymers that have been extensively studied for applications in tissue engineering (TE). The inherent biocompatibility, biodegradability, piezoelectric properties (PEs), and mechanical strength of this biological macromolecule make it an attractive candidate for scaffold fabrication, as its degradation by‐products exhibit very low cytotoxicity. Despite these advantages, PHB exhibits intrinsic limitations such as hydrophobicity, slow degradation rate, and brittleness, which restrict its broader applicability. To overcome these challenges, various modification strategies, including blending, nanocomposite (NC) incorporation, and surface modification, have been developed to enhance its physicochemical and biological performance. This review comprehensively presents recent advancements in the design and fabrication of PHB‐based electrospun scaffolds (ES‐Ss), highlighting their structural, mechanical, and biological properties. Additionally, it explores their diverse in vitro and in vivo outcomes across multiple tissue types, including bone, cartilage, skin, cardiac, and neural tissues. This study further addresses current challenges and future perspectives to optimize PHB‐based scaffolds for clinical translation in regenerative medicine.
Gholami et al. (2026) studied this question.