Neural tissue injuries, including spinal cord damage and neurodegenerative diseases, pose a major clinical challenge due to the central nervous system’s limited regenerative capacity. Current treatments focus on stabilization and symptom management rather than functional restoration. Tissue engineering offers new therapeutic perspectives, particularly through the combination of electrospun nanofibrous scaffolds and mesenchymal stem cells (MSCs). Electrospun fibers mimic the neural extracellular matrix, providing topographical and mechanical cues that enhance MSC adhesion, viability, and neural differentiation. MSCs are multipotent stem cells with robust paracrine and immunomodulatory activity, capable of supporting regeneration and, under proper stimuli, acquiring neural-like phenotypes. This systematic review, following the PRISMA 2020 method, analyzes 77 selected articles from the last ten years to assess the potential of electrospun biopolymer scaffolds for MSC-mediated neural repair. We critically examine the scaffold’s composition (synthetic and natural polymers), fiber architecture (alignment and diameter), structural and mechanical properties (porosity and stiffness), and biofunctionalization strategies. The influence of MSC tissue sources (bone marrow, adipose, and dental pulp) on neural differentiation outcomes is also discussed. The results of a literature search show both in vitro and in vivo enhanced neural marker expression, neurite extension, and functional recovery when MSCs are seeded onto optimized electrospun scaffolds. Therefore, integrating stem cell therapy with advanced biomaterials offers a promising route to bridge the gap between neural injury and functional regeneration.

Spina bifida (SB) is a congenital malformation of the central nervous system (CNS), resulting from incomplete closure of the neural tube (NT) during early embryogenesis. Myelomeningocele (MMC), the most severe form of SB, leads to progressive neurological, orthopedic, and urological dysfunctions due to both NT developmental failure and secondary intrauterine injury (“two-hit hypothesis”). Prenatal repair of MMC has progressed considerably since the Management of Myelomeningocele Study (MOMS, 2011) trial, which showed that open fetal surgery can decrease the need for shunting and improve motor function, although it carries significant maternal risks. To address these limitations, minimally invasive techniques have been developed, with the goal of achieving similar benefits for the fetus while reducing maternal morbidity. Recent research has shifted toward regenerative strategies, integrating mesenchymal stem cells (MSCs), bioengineered scaffolds, and cell-derived products to move beyond mere mechanical protection toward true NT repair. Preclinical studies in rodent and ovine models have shown that amniotic- and placenta-derived MSCs exert neuroprotective and immunomodulatory paracrine effects, promoting angiogenesis, modulating inflammation, and supporting tissue regeneration. Minimally invasive, cell-based interventions such as Transamniotic Stem Cell Therapy (TRASCET), in preclinical rodent models, offer the possibility of very early treatment without hysterotomy, although translation remains limited by the lack of large-animal validation and long-term safety data. In parallel, advances in biomaterials, nanostructured scaffolds, and exosome-based therapies reinforce a regenerative paradigm that may improve neurological outcomes and quality of life in affected children. Ongoing translational studies are essential to optimize these approaches and define their safety and efficacy in clinical settings. This review provides an integrated overview of embryological mechanisms, diagnostic strategies, and prenatal therapeutic advances in SB treatment, with emphasis on prenatal repair, fetal surgery and emerging regenerative approaches.

Background/Objectives: Shape-memory biodegradable scaffolds (4D scaffolds) represent promising platforms for minimally invasive tissue engineering and localized drug delivery. This study investigated how two different fabrication techniques, electrospinning (ES) and extrusion-based direct ink writing (DIW), influence the structural, thermal, mechanical, shape-memory, and drug-release properties of poly(L-lactide-co-caprolactone) (PLA/PCL 70:30) scaffolds loaded with dexamethasone (DXM). Methods: DXM-loaded PLA/PCL 70:30 scaffolds were fabricated by ES and DIW. The resulting matrices were characterized in terms of morphology, mass, thickness, drug-loading efficiency, thermal properties by differential scanning calorimetry, shape-memory performance, tensile mechanical properties, and in vitro DXM release. Results: Both fabrication techniques produced DXM-loaded matrices with comparable mass and thickness and high loading efficiencies (>82%). Glass transition temperatures ranged between 33 and 39 °C, supporting thermally induced shape recovery under physiologically relevant conditions, while ES processing was associated with higher polymer crystallinity. All scaffolds exhibited shape-memory behavior, with recovery ratios exceeding 90%. ES scaffolds displayed a microporous nanofibrous architecture, whereas DIW scaffolds showed a more open and highly porous structure. These morphological differences were reflected in their mechanical behavior: ES scaffolds exhibited higher tensile strength (up to 16.5 MPa vs. 1.9 MPa) and elongation at break (up to 320% vs. 243%). Drug-release profiles were also fabrication-dependent, with ES scaffolds reaching a plateau at approximately 80% DXM release, whereas DIW scaffolds showed near-complete release within 48 h. Conclusions: Both fabrication approaches preserved the thermoresponsive shape-memory behavior of PLA/PCL 70:30 but generated distinct scaffold architectures that strongly influenced mechanical performance and DXM-release kinetics.