Keratin/Copper Complex Electrospun Nanofibers for Antibacterial Treatments: Property Investigation and In Vitro Response.

The frontiers of antibacterial materials in the biomedical field are constantly evolving since infectious diseases are a continuous threat to human health. In this work, waste-wool-derived keratin electrospun nanofibers were blended with copper by an optimized impregnation procedure to fabricate antibacterial membranes with intrinsic biological activity, excellent degradability and good cytocompatibility. The keratin/copper complex electrospun nanofibers were multi-analytically characterized and the main differences in their physical-chemical features were related to the crosslinking effect caused by Cu2+. Indeed, copper ions modified the thermal profiles, improving the thermal stability (evaluated by differential scanning calorimetry and thermogravimetry), and changed the infrared vibrational features (determined by infrared spectroscopy) and the chemical composition (studied by an X-ray energy-dispersive spectroscopy probe and optical emission spectrometry). The copper impregnation process also affected the morphology, leading to partial nanofiber swelling, as evidenced by scanning electron microscopy analyses. Then, the membranes were successfully tested as antibacterial materials against gram-negative bacteria, Escherichia coli. Regarding cytocompatibility, in vitro assays performed with L929 cells showed good levels of cell adhesion and proliferation (XTT assay), and no significant cytotoxic effect, in comparison to bare keratin nanofibers. Given these results, the material described in this work can be suitable for use as antibiotic-free fibers for skin wound dressing or membranes for guided tissue regeneration.

Biomineralization of Polyelectrolyte-Functionalized Electrospun Fibers: Optimization and In Vitro Validation for Bone Applications.

In recent years, polyelectrolytes have been successfully used as an alternative to non-collagenous proteins to promote interfibrillar biomineralization, to reproduce the spatial intercalation of mineral phases among collagen fibrils, and to design bioinspired scaffolds for hard tissue regeneration. Herein, hybrid nanofibers were fabricated via electrospinning, by using a mixture of Poly ɛ-caprolactone (PCL) and cationic cellulose derivatives, i.e., cellulose-bearing imidazolium tosylate (CIMD). The obtained fibers were self-assembled with Sodium Alginate (SA) by polyelectrolyte interactions with CIMD onto the fiber surface and, then, treated with simulated body fluid (SBF) to promote the precipitation of calcium phosphate (CaP) deposits. FTIR analysis confirmed the presence of SA and CaP, while SEM equipped with EDX analysis mapped the calcium phosphate constituent elements, estimating an average Ca/P ratio of about 1.33-falling in the range of biological apatites. Moreover, in vitro studies have confirmed the good response of mesenchymal cells (hMSCs) on biomineralized samples, since day 3, with a significant improvement in the presence of SA, due to the interaction of SA with CaP deposits. More interestingly, after a decay of metabolic activity on day 7, a relevant increase in cell proliferation can be recognized, in agreement with the beginning of the differentiation phase, confirmed by ALP results. Antibacterial tests performed by using different bacteria populations confirmed that nanofibers with an SA-CIMD complex show an optimal inhibitory response against S. mutans, S. aureus, and E. coli, with no significant decay due to the effect of CaP, in comparison with non-biomineralized controls. All these data suggest a promising use of these biomineralized fibers as bioinspired membranes with efficient antimicrobial and osteoconductive cues suitable to support bone healing/regeneration.

Designing Advanced Drug Delivery Systems: Core-Shell Alginate Particles through Electro-Fluid Dynamic Atomization.

Innovations in drug delivery systems are crucial for enhancing therapeutic efficiency. Our research presents a novel approach based on using electro-fluid dynamic atomization (EFDA) to fabricate core-shell monophasic particles (CSMp) from sodium alginate blends of varying molecular weights. This study explores the morphological characteristics of these particles in relation to material properties and process conditions, highlighting their potential in drug delivery applications. A key aspect of our work is the development of a mathematical model that simulates the release kinetics of small molecules, specifically sodium diclofenac. By assessing the diffusion properties of different molecules and gel formulations through transport and rheological models, we have created a predictive tool for evaluating the efficiency of these particles in drug delivery. Our findings underscore two critical, independent parameters for optimizing drug release: the external shell thickness and the diffusivity ratios within the dual layers. This allows for precise control over the timing and intensity of the release profile. This study advances our understanding of EFDA in the fabrication of CSMp and offers promising avenues for enhancing drug delivery systems by tailoring release profiles through particle characteristic manipulation.

Micro- and Nanostructured Fibrous Composites via Electro-Fluid Dynamics: Design and Applications for Brain.

The brain consists of an interconnected network of neurons tightly packed in the extracellular matrix (ECM) to form complex and heterogeneous composite tissue. According to recent biomimicry approaches that consider biological features as active components of biomaterials, designing a highly reproducible microenvironment for brain cells can represent a key tool for tissue repair and regeneration. Indeed, this is crucial to support cell growth, mitigate inflammation phenomena and provide adequate structural properties needed to support the damaged tissue, corroborating the activity of the vascular network and ultimately the functionality of neurons. In this context, electro-fluid dynamic techniques (EFDTs), i.e., electrospinning, electrospraying and related techniques, offer the opportunity to engineer a wide variety of composite substrates by integrating fibers, particles, and hydrogels at different scales-from several hundred microns down to tens of nanometers-for the generation of countless patterns of physical and biochemical cues suitable for influencing the in vitro response of coexistent brain cell populations mediated by the surrounding microenvironment. In this review, an overview of the different technological approaches-based on EFDTs-for engineering fibrous and/or particle-loaded composite substrates will be proposed. The second section of this review will primarily focus on describing current and future approaches to the use of composites for brain applications, ranging from therapeutic to diagnostic/theranostic use and from repair to regeneration, with the ultimate goal of providing insightful information to guide future research efforts toward the development of more efficient and reliable solutions.

Sodium Alginate- and Cationic Cellulose-Functionalized Polycaprolactone Nanofibers for In Vitro and Antibacterial Applications.

The use of polyelectrolytes is emerging as a fascinating strategy for the functionalization of biomedical membranes, due to their ability to enhance biological responses using the interaction effect of charged groups on multiple interface properties. Herein, two different polyelectrolytes were used to improve the antibacterial properties of polycaprolactone (PCL) nanofibers fabricated via electrospinning. First, a new cationic cellulose derivative, cellulose-bearing imidazolium tosylate (CIMD), was prepared via the nucleophilic substitution of the tosyl group using 1-methylimidazole, as confirmed by NMR analyses, and loaded into the PCL nanofibers. Secondly, sodium alginate (SA) was used to uniformly coat the fibers' surface via self-assembly, as remarked through SEM-EDX analyses. Polyelectrolyte interactions between the CIMD and the SA, initially detected using a FTIR analysis, were confirmed via Z potential measurements: the formation of a CMID/SA complex promoted a substantial charge neutralization of the fibers' surfaces with effects on the physical properties of the membrane in terms of water adsorption and in vitro degradation. Moreover, the presence of SA contributed to the in vitro response of human mesenchymal stem cells (hMSCs), as confirmed by a significant increase in the cells' viability after 7 days in the case of the PCL/CMID/SA complex with respect to the PCL and PCL/CMID membranes. Contrariwise, SA did not nullify the antibacterial effect of CMID, as confirmed by the comparable resistance exhibited by S. mutans, S. aureus, and E. coli to the PCL/CIMD and PCL/CIMD/SA membranes. All the reported results corroborate the idea that the CIMD/SA functionalization of PCL nanofibers has a great potential for the fabrication of efficient antimicrobial membranes for wound healing.

Mineralized Microgels via Electrohydrodynamic Atomization: Optimization and In Vitro Model for Dentin-Pulp Complex.

There is growing interest in the use of micro-sized hydrogels, including bioactive signals, as efficient platforms for tissue regeneration because they are able to mimic cell niche structure and selected functionalities. Herein, it is proposed to optimize bioactive composite microgels via electrohydrodynamic atomization (EHDA) to regenerate the dentin-pulp complex. The addition of disodium phosphate (Na2HPO4) salts as mineral precursors triggered an in situ reaction with divalent ions in solution, thus promoting the encapsulation of different amounts of apatite-like phases. Morphological analysis via image analysis of optical images confirmed a narrow distribution of perfectly rounded particles, with an average diameter ranging from 223 ± 18 µm to 502 ± 64 µm as a function of mineral content and process parameters used. FTIR, TEM, and EDAX analyses confirmed the formation of calcium phosphates with a characteristic Ca/P ratio close to 1.67 and a needle-like crystal shape. In vitro studies-using dental pulp stem cells (DPSCs) in crown sections of natural teeth slices-showed an increase in cell viability until 14 days, recording a decay of proliferation at 21 days, independent on the mineral amount, suggesting that differentiation is started, as confirmed by the increase of ALP activity at 14 days. In this view, mineralized microgels could be successfully used to support in vitro osteogenesis, working as an interesting model to study dental tissue regeneration.

Synthesis and Characterization of Ciprofloxacin Loaded Star-Shaped Polycaprolactone-Polyethylene Glycol Hydrogels for Oral Delivery.

The administration of poorly water-soluble drugs represents a relevant problem due to the low body fluids transport efficiency through hydrophilic hydrogels. Star-shaped co-polymers, i.e., amphiphilic polymers such as those with a hydrophobic core and a hydrophilic outer shell, can be used to improve weak interactions with drugs, with relevant benefits in terms of administration and controlled delivery. In this work, two different co-polymers, four-arm star-shaped PCL-PEG and six-arm star-shaped PCL-PEG, were synthesized via ring-opening polymerization to be loaded with ciprofloxacin. 1H-NMR and FTIR analyses confirmed that PCL arms were successfully grafted to the mPEG backbone, while DSC analysis indicated similar crystallinity and melting point, ranging from 56 to 60 °C, independent of the different co-polymer architecture. Therefore, both star-shaped PCL-PEGs were investigated as cargo device for ciprofloxacin. No significant differences were observed in terms of drug entrapment efficiency (>95%) and drug release, characterized by a pronounced burst followed by a slow sustained release, only slightly affected by the co-polymer architecture. This result was also confirmed with curve fitting via the Korsmeyer-Peppas model. Lastly, good antibacterial properties and biocompatibility exhibited in both star-shaped PCL-PEG co-polymers suggest a promising use for oral delivery applications.

Green Routes for Bio-Fabrication in Biomedical and Pharmaceutical Applications.

In the last decade, significant advances in nanotechnologies, rising from increasing knowledge and refining of technical practices in green chemistry and bioengineering, enabled the design of innovative devices suitable for different biomedical applications. In particular, novel bio-sustainable methodologies are developing to fabricate drug delivery systems able to sagely mix properties of materials (i.e., biocompatibility, biodegradability) and bioactive molecules (i.e., bioavailability, selectivity, chemical stability), as a function of the current demands for the health market. The present work aims to provide an overview of recent developments in the bio-fabrication methods for designing innovative green platforms, emphasizing the relevant impact on current and future biomedical and pharmaceutical applications.

Optimization of PVDF-TrFE Based Electro-Conductive Nanofibers: Morphology and In Vitro Response.

In this study, morphology and in vitro response of electroconductive composite nanofibers were explored for biomedical use. The composite nanofibers were prepared by blending the piezoelectric polymer poly(vinylidene fluoride-trifluorethylene) (PVDF-TrFE) and electroconductive materials with different physical and chemical properties such as copper oxide (CuO), poly(3-hexylthiophene) (P3HT), copper phthalocyanine (CuPc), and methylene blue (MB) resulting in unique combinations of electrical conductivity, biocompatibility, and other desirable properties. Morphological investigation via SEM analysis has remarked some differences in fiber size as a function of the electroconductive phase used, with a reduction of fiber diameters for the composite fibers of 12.43% for CuO, 32.87% for CuPc, 36.46% for P3HT, and 63% for MB. This effect is related to the peculiar electroconductive behavior of fibers: measurements of electrical properties showed the highest ability to transport charges of methylene blue, in accordance with the lowest fibers diameters, while P3HT poorly conducts in air but improves charge transfer during the fiber formation. In vitro assays showed a tunable response of fibers in terms of viability, underlining a preferential interaction of fibroblast cells to P3HT-loaded fibers that can be considered the most suitable for use in biomedical applications. These results provide valuable information for future studies to be addressed at optimizing the properties of composite nanofibers for potential applications in bioengineering and bioelectronics.

PCL/Gelatin/Graphene Oxide Electrospun Nanofibers: Effect of Surface Functionalization on In Vitro and Antibacterial Response.

The emergence of resistance to pathogenic bacteria has resulted from the misuse of antibiotics used in wound treatment. Therefore, nanomaterial-based agents can be used to overcome these limitations. In this study, polycaprolactone (PCL)/gelatin/graphene oxide electrospun nanofibers (PGO) are functionalized via plasma treatment with the monomeric groups diallylamine (PGO-M1), acrylic acid (PGO-M2), and tert-butyl acrylate (PGO-M3) to enhance the action against bacteria cells. The surface functionalization influences the morphology, surface wettability, mechanical properties, and thermal stability of PGO nanofibers. PGO-M1 and PGO-M2 exhibit good antibacterial activity against Staphylococcus aureus and Escherichia coli, whereas PGO-M3 tends to reduce their antibacterial properties compared to PGO nanofibers. The highest proportion of dead bacteria cells is found on the surface of hydrophilic PGO-M1, whereas live cells are colonized on the surface of hydrophobic PGO-M3. Likewise, PGO-M1 shows a good interaction with L929, which is confirmed by the high levels of adhesion and proliferation with respect to the control. All the results confirm that surface functionalization can be strategically used as a tool to engineer PGO nanofibers with controlled antibacterial properties for the fabrication of highly versatile devices suitable for different applications (e.g., health, environmental pollution).

Bacterial Cellulose/Cellulose Imidazolium Bio-Hybrid Membranes for In Vitro and Antimicrobial Applications.

In biomedical applications, bacterial cellulose (BC) is widely used because of its cytocompatibility, high mechanical properties, and ultrafine nanofibrillar structure. However, biomedical use of neat BC is often limited due to its lack of antimicrobial properties. In the current article, we proposed a novel technique for preparing cationic BC hydrogel through in situ incorporation of cationic water-soluble cellulose derivative, cellulose bearing imidazolium tosylate function group (Cell-IMD), in the media used for BC preparation. Different concentrations of cationic cellulose derivative (2, 4, and 6%) were embedded into a highly inter-twined BC nanofibrillar network through the in situ biosynthesis until forming cationic cellulose gels. Cationic functionalization was deeply examined by the Fourier transform infrared (FT-IR), NMR spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) methods. In vitro studies with L929 cells confirmed a good cytocompatibility of BC/cationic cellulose derivatives, and a significant increase in cell proliferation after 7 days, in the case of BC/Cell-IMD3 groups. Finally, antimicrobial assessment against Staphylococcus aureus, Streptococcus mutans, and Candida albicans was assessed, recording a good sensitivity in the case of the higher concentration of the cationic cellulose derivative. All the results suggest a promising use of cationic hybrid materials for biomedical and bio-sustainable applications (i.e., food packaging).

Magnetic Response of Nano/Microparticles into Elastomeric Electrospun Fibers.

Combining magnetic nanoparticles (MNPs) with high-voltage processes to produce ultra-thin magnetic nanofibers (MNFs) fosters the development of next-generation technologies. In this study, polycarbonate urethane nanofibers incorporating magnetic particles were produced via the electrospinning technique. Two distinct types of magnetic payload were used: (a) iron oxide nanoparticles (IONPs) with an average size and polydispersity index of 7.2 nm and 3.3%, respectively; (b) nickel particles (NiPs) exhibiting a bimodal size distribution with average sizes of 129 nanometers and 600 nanometers, respectively, and corresponding polydispersity indexes of 27.8% and 3.9%. Due to varying particle sizes, significant differences were observed in their aggregation and distribution within the nanofibers. Further, the magnetic response of the IONP and/or NiP-loaded fiber mats was consistent with their morphology and polydispersity index. In the case of IONPs, the remanence ratio (Mr/Ms) and the coercive field (Hc) were found to be zero, which agrees with their superparamagnetic behavior when the average size is smaller than 20-30 nm. However, the NiPs show Mr/Ms = 22% with a coercive field of 0.2kOe as expected for particles in a single or pseudo-single domain state interacting with each other via dipolar interaction. We conclude that magnetic properties can be modulated by controlling the average size and polydispersity index of the magnetic particles embedded in fiber mats to design magneto-active systems suitable for different applications (i.e., wound healing and drug delivery).

New Insights to Design Electrospun Fibers with Tunable Electrical Conductive-Semiconductive Properties.

Fiber electronics, such as those produced by the electrospinning technique, have an extensive range of applications including electrode surfaces for batteries and sensors, energy storage, electromagnetic interference shielding, antistatic coatings, catalysts, drug delivery, tissue engineering, and smart textiles. New composite materials and blends from conductive-semiconductive polymers (C-SPs) offer high surface area-to-volume ratios with electrical tunability, making them suitable for use in fields including electronics, biofiltration, tissue engineering, biosensors, and "green polymers". These materials and structures show great potential for embedded-electronics tissue engineering, active drug delivery, and smart biosensing due to their electronic transport behavior and mechanical flexibility with effective biocompatibility. Doping, processing methods, and morphologies can significantly impact the properties and performance of C-SPs and their composites. This review provides an overview of the current literature on the processing of C-SPs as nanomaterials and nanofibrous structures, mainly emphasizing the electroactive properties that make these structures suitable for various applications.

Hyaluronic Acid in Biomedical Fields: New Trends from Chemistry to Biomaterial Applications.

The aim of this review is to give an updated perspective about the methods for chemical modifications of hyaluronic acid (HA) toward the development of new applications in medical devices and material engineering. After a brief introduction on chemical, structural and biological features of this important natural polysaccharide, the most important methods for chemical and physical modifications are disclosed, discussing both on the formation of new covalent bonds and the interaction with other natural polysaccharides. These strategies are of paramount importance in the production of new medical devices and materials with improved properties. In particular, the use of HA in the development of new materials by means of additive manufacturing techniques as electro fluid dynamics, i.e., electrospinning for micro to nanofibres, and three-dimensional bioprinting is also discussed.

Electro Fluid Dynamics: A Route to Design Polymers and Composites for Biomedical and Bio-Sustainable Applications.

In the last two decades, several processes have been explored for the development of micro and/or nanostructured substrates by sagely physically and/or chemically manipulating polymer materials. These processes have to be designed to overcome some of the limitations of the traditional ones in terms of feasibility, reproducibility, and sustainability. Herein, the primary aim of this work is to focus on the enormous potential of using a high voltage electric field to manipulate polymers from synthetic and/or natural sources for the fabrication of different devices based on elementary units, i.e., fibers or particles, with different characteristic sizes-from micro to nanoscale. Firstly, basic principles and working mechanisms will be introduced in order to correlate the effect of selected process parameters (i.e., an applied voltage) on the dimensional features of the structures. Secondly, a comprehensive overview of the recent trends and potential uses of these processes will be proposed for different biomedical and bio-sustainable application areas.

Coupling of 3-Aminopropyl Sulfonic Acid to Cellulose Nanofibers for Efficient Removal of Cationic Dyes.

A novel anionic nanostructured cellulose derivate was prepared through the coupling of TEMPO-oxidized cellulose nanofibers with 3-aminopropyl sulfonic acid (3-APSA). 3-APSA grafting was variously investigated by FT-IR spectroscopy and transmission electron microscopy (TEM) analysis, confirming a high reaction degree. The surface morphology investigated via scanning electron microscopy (SEM) revealed a more uniform organization of the nanofibers after the 3-APSA coupling, with improvements in terms of fiber packing and pore interconnectivity. This peculiar morphology contributes to improving methylene blue (MB) adsorption and removal efficiency at different operating conditions (pH, initial time, and initial concentration). The results indicated a maximum adsorption capacity of 526 mg/g in the case of 3-APSA grafted nanofibers, over 30% more than that of non-grafted ones (370 mg/g), which confirm a relevant effect of chemical modification on the adsorbent properties of cellulose nanofibers. The adsorption kinetics and isotherms of the current adsorbents match with the pseudo-second-order kinetic and Langmuir isotherm models. This study suggests the use of chemical grafting via 3-APSA is a reliable and facile post-treatment to design bio-sustainable and reusable nanofibers to be used as high-performance adsorbent materials in water pollutant remediation.

3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization.

In the last decade, different technological approaches have been proposed for the fabrication of 3D models suitable to evaluate in vitro cell response. Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). In this work, a method to fabricate 3D scaffolds by the assembly of bicomponent microgels made of sodium alginate and gelatin was proposed. As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). Chemical analysis via ninhydrin essays and FTIR analysis confirmed the presence of gelatin, mostly retained by physical interactions into the alginate network mediated by electrostatic forces. In vitro tests confirmed the effect of biochemical signals exerted by the protein on the biological response of hMSCs cultured onto the microgels surface. Hence, it is concluded that alginate/gelatin microgels assemblies can efficiently work as 3D scaffolds able to support in vitro cells functions, thus providing a friendly microenvironment to investigate in vitro cell interactions.

Electrospun Sulfonatocalix[4]arene Loaded Blended Nanofibers: Process Optimization and In Vitro Studies.

In the past decade, electrospun nanofibers made of biodegradable polymers have been used for different biomedical applications due to their flexible features in terms of surface area to volume ratio, pores, and fiber size, as well as their highly tunable surface properties. Recently, interest is growing in the use of supramolecular structures in combination with electrospun nanofibers for the fabrication of bioactive platforms with improved in vitro responses, to be used for innovative therapeutic treatments. Herein, sulfonatocalix[4]arene (SCX4) was synthesized from p-tert-butyl-calix[4]arene and embedded in electrospun nanofibers made of polycaprolactone (PCL) and gelatin (GEL). The supramolecular structure of SCX4 and its efficient entrapment into electrospun fibers was confirmed by NMR spectroscopy and FTIR analysis, respectively. SEM analysis supported via image analysis enabled the investigation of the fiber morphology at the sub-micrometric scale, showing a drastic reduction in fiber diameters in the presence of SCX4: 267 ± 14 nm (without SCX) to 115 ± 5 nm (3% SCX4). Moreover, it was demonstrated that SCX4 significantly contributes to the hydrophilic properties of the fiber surface, as was confirmed by the reduction in contact angles from 54 ± 1.4° to 31 ± 5.5° as the SCX4 amount increased, while no effects on thermal stability were recognized, as was confirmed by TGA analyses. In vitro tests also confirmed that SCX4 is not cytotoxic, but plays a supporting role in L929 interactions, as was validated by the cell viability of PGC15% after 7 days, with respect to the control. These preliminary but promising data suggest their use for the fabrication of innovative platforms able to bind SCX4 to bioactive compounds and molecules for different therapeutic applications, from molecular recognition to controlled drug delivery.

3D-Printed Tubular Scaffolds Decorated with Air-Jet-Spun Fibers for Bone Tissue Applications.

The fabrication of instructive materials to engineer bone substitute scaffolds is still a relevant challenge. Current advances in additive manufacturing techniques make possible the fabrication of 3D scaffolds with even more controlled architecture at micro- and submicrometric levels, satisfying the relevant biological and mechanical requirements for tissue engineering. In this view, integrated use of additive manufacturing techniques is proposed, by combining 3D printing and air-jet spinning techniques, to optimize the fabrication of PLA tubes with nanostructured fibrous coatings for long bone defects. The physicochemical characterization of the 3D tubular scaffolds was performed by scanning electron microscopy, thermogravimetric analysis, differential scanning calorimetry, profilometry, and mechanical properties. In vitro biocompatibility was evaluated in terms of cell adhesion, proliferation, and cell-material interactions, by using human fetal osteoblasts to validate their use as a bone growth guide. The results showed that 3D-printed scaffolds provide a 3D architecture with highly reproducible properties in terms of mechanical and thermal properties. Moreover, nanofibers are collected onto the surface, which allows forming an intricate and interconnected network that provides microretentive cues able to improve adhesion and cell growth response. Therefore, the proposed approach could be suggested to design innovative scaffolds with improved interface properties to support regeneration mechanisms in long bone treatment.

Polydopamine-Coated Poly-Lactic Acid Aerogels as Scaffolds for Tissue Engineering Applications.

Poly-L-lactic acid (PLLA) aerogel-based scaffolds were obtained from physical PLLA gels containing cyclopentanone (CPO) or methyl benzoate (BzOMe) molecules. An innovative single step method of solvent extraction, using supercritical CO2, was used to achieve cylindrical monolithic aerogels. The pore distribution and size, analyzed by SEM microscopy, were found to be related to the crystalline forms present in the physical nodes that hold the gels together, the stable α'-form and the metastable co-crystalline ε-form, detected in the PLLA/BzOMe and PLLA/CPO aerogels, respectively. A higher mechanical compressive strength was found for the PLLA/CPO aerogels, which exhibit a more homogenous porosity. In vitro biocompatibility tests also indicated that monolithic PLLA/CPO aerogels exhibited greater cell viability than PLLA/BzOMe aerogels. An improved biocompatibility of PLLA/CPO monolithic aerogels was finally observed by coating the surface of the aerogels with polydopamine (PDA) obtained by the in situ polymerization of dopamine (DA). The synergistic effect of biodegradable polyester (PLLA) and the biomimetic interface (PDA) makes this new 3D porous scaffold, with porosity and mechanical properties that are tunable based on the solvent used in the preparation process, attractive for tissue engineering applications.