Controlled Release of H2S from Biomimetic Silk Fibroin-PLGA Multilayer Electrospun Scaffolds.

The possibility of incorporating H2S slow-release donors inside biomimetic scaffolds can pave the way to new approaches in the field of tissue regeneration and anti-inflammatory treatment. In the present work, GYY4137, an easy-to-handle commercially available Lawesson's reagent derivative, has been successfully incorporated inside biomimetic silk fibroin-based electrospun scaffolds. Due to the instability of GYY4137 in the solvent needed to prepare silk fibroin solutions (formic acid), the electrospinning of the donor together with the silk fibroin turned out to be impossible. Therefore, a multilayer structure was realized, consisting of a PLGA mat containing GYY4137 sandwiched between two silk fibroin nanofibrous layers. Before their use in the multilayer scaffold, the silk fibroin mats were treated in ethanol to induce crystalline phase formation, which conferred water-resistance and biomimetic properties. The morphological, thermal, and chemical properties of the obtained scaffolds were thoroughly characterized by SEM, TGA, DSC, FTIR, and WAXD. Multilayer devices showing two different concentrations of the H2S donor, i.e., 2 and 5% w/w with respect to the weight of PLGA, were analyzed to study their H2S release and biological properties, and the results were compared with those of the sample not containing GYY4137. The H2S release analysis was carried out according to an "ad-hoc" designed procedure based on a validated high-performance liquid chromatography method. The proposed analytical approach demonstrated the slow-release kinetics of H2S from the multilayer scaffolds and its tunability by acting on the donor's concentration inside the PLGA nanofibers. Finally, the devices were tested in biological assays using bone marrow-derived mesenchymal stromal cells showing the capacity to support cell spreading throughout the scaffold and prevent cytotoxicity effects in serum starvation conditions. The resulting devices can be exploited for applications in the tissue engineering field since they combine the advantages of controlled H2S release kinetics and the biomimetic properties of silk fibroin nanofibers.

Thermoactive Smart Electrospun Nanofibers.

The recent burst of research on smart materials is a clear evidence of the growing interest of the scientific community, industry, and society in the field. The exploitation of the great potential of stimuli-responsive materials for sensing, actuation, logic, and control applications is favored and supported by new manufacturing technologies, such as electrospinning, that allows to endow smart materials with micro- and nanostructuration, thus opening up additional and unprecedented prospects. In this wide and lively scenario, this article systematically reviews the current advances in the development of thermoactive electrospun fibers and textiles, sorting them, according to their response to the thermal stimulus. Hence, several platforms including thermoresponsive systems, shape memory polymers, thermo-optically responsive systems, phase change materials, thermoelectric materials, and pyroelectric materials, are described and critically discussed. The difference in active species and outputs of the aforementioned categories is highlighted, evidencing the transversal nature of temperature stimulus. Moreover, the potential of novel thermoactive materials are pointed out, revealing how their development could take to utmost interesting achievements.

A Modular Composite Device of Poly(Ethylene Oxide)/Poly(Butylene Terephthalate) (PEOT/PBT) Nanofibers and Gelatin as a Dual Drug Delivery System for Local Therapy of Soft Tissue Tumors.

In the clinical management of solid tumors, the possibility to successfully couple the regeneration of injured tissues with the elimination of residual tumor cells left after surgery could open doors to new therapeutic strategies. In this work, we present a composite hydrogel-electrospun nanofiber scaffold, showing a modular architecture for the delivery of two pharmaceutics with distinct release profiles, that is potentially suitable for local therapy and post-surgical treatment of solid soft tumors. The composite was obtained by coupling gelatin hydrogels to poly(ethylene oxide)/poly(butylene terephthalate) block copolymer nanofibers. Results of the scaffolds' characterization, together with the analysis of gelatin and drug release kinetics, displayed the possibility to modulate the device architecture to control the release kinetics of the drugs, also providing evidence of their activity. In vitro analyses were also performed using a human epithelioid sarcoma cell line. Furthermore, publicly available expression datasets were interrogated. Confocal imaging showcased the nontoxicity of these devices in vitro. ELISA assays confirmed a modulation of IL-10 inflammation-related cytokine supporting the role of this device in tissue repair. In silico analysis confirmed the role of IL-10 in solid tumors including 262 patients affected by sarcoma as a negative prognostic marker for overall survival. In conclusion, the developed modular composite device may provide a key-enabling technology for the treatment of soft tissue sarcoma.

Combining Biologically Active ß-Lactams Integrin Agonists with Poly(l-lactic acid) Nanofibers: Enhancement of Human Mesenchymal Stem Cell Adhesion.

Regulating stem cell adhesion and growth onto functionalized biomaterial scaffolds is an important issue in the field of tissue engineering and regenerative medicine. In this study, new electrospun scaffolds of poly(l-lactic acid) (PLLA), as bioresorbable polymer, and ß-lactam compounds agonists of selected integrins, as functional components with cell adhesive properties, are designed. The new ß-lactam-PLLA scaffolds contribute significantly in guiding protein translation involved in human bone marrow mesenchymal stem cells (hBM-MSC) adhesion and integrin gene expression. Scanning electron microscopy, confocal laser scanning microscopy, and Western Blot analyses reveal that GM18-PLLA shows the best results, promoting cell adhesion by significantly driving changes in focal adhesion proteins distribution (ß1 integrin and vinculin) and activation (pFAK), with a notable increase of GM18-targets subunits integrin gene expression, α4 and ß1. These novel functionalized submicrometric fibrous scaffolds demonstrate, for the first time, the powerful combination of selective ß-lactams agonists of integrins with biomimetic scaffolds, suggesting a designed rule that could be suitably applied to tissue repair and regeneration.

Ether-Oxygen Containing Electrospun Microfibrous and Sub-Microfibrous Scaffolds Based on Poly(butylene 1,4-cyclohexanedicarboxylate) for Skeletal Muscle Tissue Engineering.

We report the study of novel biodegradable electrospun scaffolds from poly(butylene 1,4-cyclohexandicarboxylate-co-triethylene cyclohexanedicarboxylate) (P(BCE-co-TECE)) as support for in vitro and in vivo muscle tissue regeneration. We demonstrate that chemical composition, i.e., the amount of TECE co-units (constituted of polyethylene glycol-like moieties), and fibre morphology, i.e., aligned microfibrous or sub-microfibrous scaffolds, are crucial in determining the material biocompatibility. Indeed, the presence of ether linkages influences surface wettability, mechanical properties, hydrolytic degradation rate, and density of cell anchoring points of the studied materials. On the other hand, electrospun scaffolds improve cell adhesion, proliferation, and differentiation by favouring cell alignment along fibre direction (fibre morphology), also allowing for better cell infiltration and oxygen and nutrient diffusion (fibre size). Overall, C2C12 myogenic cells highly differentiated into mature myotubes when cultured on microfibres realised with the copolymer richest in TECE co-units (micro-P73 mat). Lastly, when transplanted in the tibialis anterior muscles of healthy, injured, or dystrophic mice, micro-P73 mat appeared highly vascularised, colonised by murine cells and perfectly integrated with host muscles, thus confirming the suitability of P(BCE-co-TECE) scaffolds as substrates for skeletal muscle tissue engineering.

Poly-Gamma-Glutamic Acid (γ-PGA)-Based Encapsulation of Adenovirus to Evade Neutralizing Antibodies.

In recent years, there has been an increasing interest in oncolytic adenoviral vectors as an alternative anticancer therapy. The induction of an immune response can be considered as a major limitation of this kind of application. Significant research efforts have been focused on the development of biodegradable polymer poly-gamma-glutamic acid (γ-PGA)-based nanoparticles used as a vector for effective and safe anticancer therapy, owing to their controlled and sustained-release properties, low toxicity, as well as biocompatibility with tissue and cells. This study aimed to introduce a specific destructive and antibody blind polymer-coated viral vector into cancer cells using γ-PGA and chitosan (CH). Adenovirus was successfully encapsulated into the biopolymer particles with an encapsulation efficiency of 92% and particle size of 485 nm using the ionic gelation method. Therapeutic agents or nanoparticles (NPs) that carry therapeutics can be directed specifically to cancerous cells by decorating their surfaces using targeting ligands. Moreover, in vitro neutralizing antibody response against viral capsid proteins can be somewhat reduced by encapsulating adenovirus into γ-PGA-CH NPs, as only 3.1% of the encapsulated adenovirus was detected by anti-adenovirus antibodies in the presented work compared to naked adenoviruses. The results obtained and the unique characteristics of the polymer established in this research could provide a reference for the coating and controlled release of viral vectors used in anticancer therapy.

Thermal Annealing to Modulate the Shape Memory Behavior of a Biobased and Biocompatible Triblock Copolymer Scaffold in the Human Body Temperature Range.

A biodegradable and biocompatible electrospun scaffold with shape memory behavior in the physiological temperature range is here presented. It was obtained starting from a specifically designed, biobased PLLA-based triblock copolymer, where the central block is poly(propylene azelate-co-propylene sebacate) (P(PAz60PSeb40)) random copolymer. Shape memory properties are determined by the contemporary presence of the low melting crystals of the P(PAz60PSeb40) block, acting as switching segment, and of the high melting crystal phase of PLLA blocks, acting as physical network. It is demonstrated that a straightforward annealing process applied to the crystal phase of the switching element gives the possibility to tune the shape recovery temperature from about 25 to 50 °C, without the need of varying the copolymer's chemical structure. The thermal annealing approach here presented can be thus considered a powerful strategy for "ad hoc" programming the same material for applications requiring different recovery temperatures. Fibroblast culture experiments demonstrated scaffold biocompatibility.

Pseudopeptide-Based Hydrogels Trapping Methylene Blue and Eosin†Y.

We present herein the preparation of four different hydrogels based on the pseudopeptide gelator Fmoc-l-Phe-d-Oxd-OH (Fmoc=fluorenylmethyloxycarbonyl), either by changing the gelator concentration or adding graphene oxide (GO) to the water solution. The hydrogels have been analysed by rheological studies that demonstrated that pure hydrogels are slightly stronger compared to GO-loaded hydrogels. Then the hydrogels efficiency to trap the cationic methylene blue (MB) and anionic eosin Y (EY) dyes has been analyzed. MB is efficiently trapped by both the pure hydrogel and the GO-loaded hydrogel through π-π interactions and electrostatic interactions. In contrast, the removal of the anionic EY is achieved in less satisfactory yields, due to the unfavourable electrostatic interactions between the dye, the gelator and GO.

Hydrogelation Induced by Fmoc-Protected Peptidomimetics.

Four new low molecular weight hydrogelators (LMWGs) have been prepared in multigram scale and their attitude to form hydrogels has been tested. The gelation trigger is pH variation. The resulting gels have been characterized with several techniques: measurement of the melting points (T(gel)), transparency, gelation time, and viscoelastic properties, together with ECD analysis. Among them, Fmoc-L-Tyr-D-Oxd-OH 1 is an excellent gelator that leads to the preparation of strong, transparent, and viscoelastic gels, by pH variation. UV-visible analyses have demonstrated that the gels obtained with the LMWG 1 possess high transparency, with a transmittance up to 25.6% at a wavelength of 600 nm. Results of the amplitude sweep experiments showed that the elastic response component (G') was approximately an order of magnitude larger than the viscous component, indicating an elastic rather than viscous attitude of the gels, confirmed by the frequency independence of G' and G″ values, in the range from 0.1 to 100 rad·s(-1). The thermal behavior of gel obtained from Fmoc-L-Tyr-D-Oxd-OH 1 was characterized performing an "ad hoc" rheological temperature sweep experiment, that indicated that G' remained almost constant from 23 °C up to about 65 °C while G″ increased in the same temperature range. At higher temperatures, both G' and G″ values started to slightly decrease without displaying a crossover point.

The role of 3D microenvironmental organization in MCF-7 epithelial-mesenchymal transition after 7 culture days.

We present a multi-technique study on in vitro epithelial-mesenchymal transition (EMT) in human MCF-7 cells cultured on electrospun scaffolds of poly(l-lactic acid) (PLA), with random and aligned fiber orientations. Our aim is to investigate the morphological and genetic characteristics induced by extracellular matrix in tumor cells cultured in different 3D environments, and at different time points. Cell vitality was assessed with AlamarBlue at days 1, 3, 5 and 7. Scanning electron microscopy was performed at culture days 3 and 7. Immunohistochemistry (for E-cadherin, ß-catenin, cytokeratins, nucleophosmin, tubulin, Ki-67 and vimentin), immunofluorescence (for F-actin) western blot (for E-cadherin, ß-catenin and vimentin) and transmission electron microscopy were carried out at day 7. An EMT gene array followed by PCR analysis confirmed the regulation of selected genes. At day 7, scanning electron microscopy on aligned-PLA revealed spindle-shaped cells gathered in buds and ribbon-like structures, with a higher nucleolar/nuclear ratio and a loss in E-cadherin and ß-catenin at immunohistochemistry and western blot. An up-regulation of SMAD2, TGF-ß2, TFPI2 and SOX10 was found in aligned-PLA compared to random-PLA cultured cells. The topography of the extracellular matrix has a role in tumor EMT, and a more aggressive phenotype characterizes MCF-7 cells cultured on aligned-PLA scaffold.

Comparative performance of collagen nanofibers electrospun from different solvents and stabilized by different crosslinkers.

Collagen electrospun scaffolds well reproduce the structure of the extracellular matrix (ECM) of natural tissues by coupling high biomimetism of the biological material with the fibrous morphology of the protein. Structural properties of collagen electrospun fibers are still a debated subject and there are conflicting reports in the literature addressing the presence of ultrastructure of collagen in electrospun fibers. In this work collagen type I was successfully electrospun from two different solvents, trifluoroethanol (TFE) and dilute acetic acid (AcOH). Characterization of collagen fibers was performed by means of SEM, ATR-IR, Circular Dichroism and WAXD. We demonstrated that collagen fibers contained a very low amount of triple helix with respect to pristine collagen (18 and 16% in fibers electrospun from AcOH and TFE, respectively) and that triple helix denaturation occurred during polymer dissolution. Collagen scaffolds were crosslinked by using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), a commonly employed crosslinker for electrospun collagen, and 1,4-butanediol diglycidyl ether (BDDGE), that was tested for the first time in this work as crosslinking agent for collagen in the form of electrospun fibers. We demonstrated that BDDGE successfully crosslinked collagen and preserved at the same time the scaffold fibrous morphology, while scaffolds crosslinked with EDC completely lost their porous structure. Mesenchymal stem cell experiments demonstrated that collagen scaffolds crosslinked with BDDGE are biocompatible and support cell attachment.

Nanovascularization of polymer matrix: generation of nanochannels and nanotubes by sacrificial electrospun fibers.

Several methods for creating vascular structures, made of either discrete or interconnected channels have been developed. The currently employed methods enable the formation of channels with diameters in the millimetric and micrometric scale. However, the formation of an interconnected three-dimensional (3D) vasculature by using a rapid and scalable process is a challenge and largely limits the fields of applicability of these innovative materials. Here, we propose the use of electrospun nonwoven mats as sacrificial fibers to easily generate 3D macroscale vascularized composites containing interconnected networks with channels and tubes having submicrometric and nanometric diameters. The novel approach has the potentialities to give rise to a novel generation of composites potentially displaying new and enhanced functionalities thanks to the nanoscale features of the cavities.

Full-field strain distribution in hierarchical electrospun nanofibrous poly-L(lactic) acid/collagen scaffolds for tendon and ligament regeneration: A multiscale study.

Regeneration of injured tendons and ligaments (T/L) is a worldwide need. In this study electrospun hierarchical scaffolds made of a poly-L (lactic) acid/collagen blend were developed reproducing all the multiscale levels of aggregation of these tissues. Scanning electron microscopy, microCT and tensile mechanical tests were carried out, including a multiscale digital volume correlation analysis to measure the full-field strain distribution of electrospun structures. The principal strains (εp1 and εp3) described the pattern of strains caused by the nanofibers rearrangement, while the deviatoric strains (εD) revealed the related internal sliding of nanofibers and bundles. The results of this study confirmed the biomimicry of such electrospun hierarchical scaffolds, paving the way to further tissue engineering and clinical applications.

Microporous electrospun nonwovens combined with green solvents for the selective peel-off of thin coatings from painting surfaces.

Over the last few decades, significant research efforts have been devoted to developing new cleaning systems aimed at preserving cultural heritage. One of the main objectives is to selectively remove aged or undesirable coatings from painted surfaces while preventing the cleaning solvent from permeating and engaging with the pictorial layers. In this work, we propose the use of electrospun polyamide 6,6 nonwovens in conjunction with a green solvent (dimethyl carbonate). By adjusting the electrospinning parameters, we produced three distinct nonwovens with varying average fiber diameters, ranging from 0.4 µm to 2 µm. These samples were characterized and tested for their efficacy in removing dammar varnish from painted surfaces. In particular, the cleaning process was monitored using macroscale PL (photoluminescence) imaging in real-time, while post-application examination of the mats was performed through scanning electron microscopy. The solvent evaporation rate from the different nonwovens was evaluated using gravimetric analysis and Proton Transfer Reaction- Time-of-Flight. It was observed that the application of the nonwovens with small or intermediate pore sizes for the removal of the terpenic varnish resulted in the swollen resin being absorbed into the mats, showcasing a peel-off effect. Thus, this protocol eliminates the need for further potentially detrimental removal procedures involving cotton swabs. The experimental data suggests that the peel-off effect relates to the microporosity of the mats, which enhances the capillary rise of the swollen varnish. Furthermore, the application of these systems to historical paintings underwent preliminary validation using a real painting from the 20th century.

Peptide direct growth on poly(acrylic acid)/poly(vinyl alcohol) electrospun fibers coated with branched poly(ethylenimine): A solid-phase approach for scaffolds biofunctionalization.

Due to their resemblance to the fibrillar structure of the extracellular matrix, electrospun nanofibrous meshes are currently used as porous and mechanically stable scaffolds for cell culture. In this study, we propose an innovative methodology for growing peptide sequences directly onto the surface of electrospun nanofibers. To achieve this, electrospun fibers were produced from a poly(acrylic acid)/poly(vinyl alcohol) blend that was thermally crosslinked and subjected to a covalent coating of branched poly(ethylenimine). The exposed amino functionalities on the fiber surface were then used for the direct solid-phase synthesis of the RGD peptide sequence. In contrast to established strategies, mainly involving the grafting of pre-synthesized peptides onto the polymer chains before electrospinning or onto the nanofibers surface, this method allows for the concurrent synthesis and anchoring of peptides to the substrate, with potential applications in combinatorial chemistry. The incorporation of this integrin-binding motive significantly enhanced the nanofibers' ability to capture human cervical carcinoma (HeLa) cells, selected as a proof of concept to assess the functionalities of the developed material.

Carbon dot/polylactic acid nanofibrous membranes for solar-mediated oil absorption/separation: Performance, environmental sustainability, ecotoxicity and reusability.

Carbon dots (CDs) are promising photothermal nanoparticles that can be utilized in environmental treatments. They exhibit favorable physicochemical properties, including low toxicity, physical and chemical stability, photo-dependant reversible behaviour, and environmentally friendly synthesis using benign building blocks. Here, we synthesized innovative CDs/polylactic acid (PLA) electrospun composite membranes for evaluating the removal of hydrophobic compounds like long-chain hydrocarbons or oils in biphasic mixtures with water. The ultimate goal was to develop innovative and sustainable solar-heated oil absorbents. Specifically, we fabricated PLA membranes with varying CD contents, characterized their morphology, thermal, and mechanical properties, and assessed the environmental impact of membrane production according to ISO 14040 and 14044 standards in a preliminary "cradle-to-gate" life cycle assessment study. Solar radiation experiments demonstrated that the CDs/PLA composites exhibited greater uptake of hydrophobic compounds compared to pure PLA membranes, ascribable to the CDs-induced photothermal effect. The adsorption and regeneration capacity of the new CDs/PLA membrane was demonstrated through multiple uptake/release cycles. Ecotoxicity analyses confirmed the safety profile of the new adsorbent system towards freshwater microalgae, further emphasizing its potential as an environmentally friendly solution for the removal of hydrophobic compounds in water treatment processes.

Emerging materials and technologies for advancing bioresorbable surgical meshes.

Surgical meshes play a significant role in the treatment of various medical conditions, such as hernias, pelvic floor issues, guided bone regeneration, and wound healing. To date, commercial surgical meshes are typically made of non-absorbable synthetic polymers, notably polypropylene and polytetrafluoroethylene, which are associated with postoperative complications, such as infections. Biological meshes, based on native tissues, have been employed to overcome such complications, though mechanical strength has been a main disadvantage. The right balance in mechanical and biological performances has been achieved by the advent of bioresorbable meshes. Despite improvements, recurrence of clinical complications associated with surgical meshes raises significant concerns regarding the technical adequacy of current materials and designs, pointing to a crucial need for further development. To this end, current research focuses on the design of meshes capable of biomimicking native tissue and facilitating the healing process without post-operative complications. Researchers are actively investigating advanced bioresorbable materials, both synthetic polymers and natural biopolymers, while also exploring the performance of therapeutic agents, surface modification methods and advanced manufacturing technologies such as 4D printing. This review seeks to evaluate emerging biomaterials and technologies for enhancing the performance and clinical applicability of the next-generation surgical meshes. STATEMENT OF SIGNIFICANCE: In the ever-transforming landscape of regenerative medicine, the embracing of engineered bioabsorbable surgical meshes stands as a key milestone in addressing persistent challenges and complications associated with existing treatments. The urgency to move beyond conventional non-absorbable meshes, fraught with post-surgery complications, emphasises the necessity of using advanced biomaterials for engineered tissue regeneration. This review critically examines the growing field of absorbable surgical meshes, considering their potential to transform clinical practice. By strategically combining mechanical strength with bioresorbable characteristics, these innovative meshes hold the promise of mitigating complications and improving patient outcomes across diverse medical applications. As we navigate the complexities of modern medicine, this exploration of engineered absorbable meshes emerges as a promising approach, offering an overall perspective on biomaterials, technologies, and strategies adopted to redefine the future of surgical meshes.

Advantages of surface-initiated ATRP (SI-ATRP) for the functionalization of electrospun materials.

Surface-initiated atom transfer radical polymerization (SI-ATRP) is successfully applied to electrospun constructs of poly(L-lactide). ATRP macroinitiators are adsorbed through polyelectrolyte complexation following the introduction of negative charges on the polyester surface through its blending with a six-armed carboxy-terminated oligolactide. SI-ATRP of glycerol monomethacrylate (GMMA) or 2-(N,N-diethylamino)ethyl methacrylate (DEAEMA) allows then to grow surface films with controllable thickness, and in this way also to control the wetting and interactions of the construct.

Nanofibers of chitosan-polycaprolactone blends as active support for photocatalytic nanoparticles: Outstanding role of chitosan in the degradation of an organic dye in water.

Hybrid nanofibers of a chitosan-polycaprolactone blend containing titanium dioxide nanoparticles TiO2NPs, were prepared through electrospinning to study their adsorption and photocatalytic degradation capabilities of the model organic water pollutants, rhodamine B, RhB. To obtain uniform and bead-free nanofibers, an optimization of the electrospinning parameters was performed. The optimization was carried out by systematically adjusting the solution conditions (solvent, concentration, and polymer ratio) and instrumental parameters (voltage, needle tip-collector distance, and flow). The obtained materials were characterized by FT-IR, TGA, DSC, SEM, TEM, mechanical tensile test, and water contact angle. The photoactivity was investigated using a batch-type system by following UV-Vis absorbance and fluorescence of RhB. TiO2NPs were incorporated ex-situ into the polymer matrix, contributing to good mechanical properties and higher hydrophilicity of the material. The results showed that the presence of chitosan in the nanofibers significantly increased the adsorption of RhB and its photocatalytic degradation by TiO2NPs (5, 55 and 80 % of RhB degradation with NFs of PCL, TiO2/PCL and TiO2/CS-PCL, after 30 h of light irradiation, respectively), evidencing a synergistic effect between them. The results are attributed to an attraction of RhB by chitosan to the vicinity of TiO2NPs, favouring initial adsorption and degradation, phenomenon known as "bait-and-hook-and-destruct" effect.

Electrospun Poly(L-lactide-co-ε-caprolactone) Scaffold Potentiates C2C12 Myoblast Bioactivity and Acts as a Stimulus for Cell Commitment in Skeletal Muscle Myogenesis.

Tissue engineering combines a scaffold, cells and regulatory signals, reproducing a biomimetic extracellular matrix capable of supporting cell attachment and proliferation. We examined the role of an electrospun scaffold made of a biocompatible polymer during the myogenesis of skeletal muscle (SKM) as an alternative approach to tissue regeneration. The engineered nanostructure was obtained by electrospinning poly(L-lactide-co-ε-caprolactone) (PLCL) in the form of a 3D porous nanofibrous scaffold further coated with collagen. C2C12 were cultured on the PLCL scaffold, and cell morphology and differentiation pathways were thoroughly investigated. The functionalized PLCL scaffold recreated the SKM nanostructure and performed its biological functions, guiding myoblast morphogenesis and promoting cell differentiation until tissue formation. The scaffold enabled cell-cell interactions through the development of cellular adhesions that were fundamental during myoblast fusion and myotube formation. Expression of myogenic regulatory markers and muscle-specific proteins at different stages of myogenesis suggested that the PLCL scaffold enhanced myoblast differentiation within a shorter time frame. The functionalized PLCL scaffold impacts myoblast bioactivity and acts as a stimulus for cell commitment, surpassing traditional 2D cell culture techniques. We developed a screening model for tissue development and a device for tissue restoration.