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The aim of this work was the assessment of the “in vivo” immune response of a poly(lactide-co-glycolide)-based nanoparticulate adjuvant for a sub-unit vaccine, namely, a purified recombinant collagen-binding bacterial adhesion fragment (CNA19), againstStaphylococcus aureus-mediated infections. “In vivo” immunogenicity studies were performed on mice: immunisation protocols encompassed subcutaneous and intranasal administration of CNA19 formulated as nanoparticles (NPs) and furthermore, CNA19-loaded NPs formulated in a set-up thermosetting chitosan-β-glycerolphosphate (chitosan-β-GP) solution for intranasal route in order to extend antigen exposure to nasal mucosa. CNA19 loaded NPs (mean size of about 195 nm, 9.04 ± 0.37μg/mg as CNA19 loading capacity) confirmed as suitable vaccine for subcutaneous administration with a more pronounced adjuvant effect (about 3-fold higher) with respect to aluminium, recognised as “reference” adjuvant. CNA19 loaded NPs formulated in an optimised thermogelling chitosan-β-GP solution showed promising results for eliciting an effective humoral response and a good chance as intranasal boosting dose. [ABSTRACT FROM PUBLISHER]

The aim was to design sterile biodegradable microparticulate drug delivery systems based on poly( dl-lactide) (PLA) and poly(ϵ-caprolactone) (PCL) and containing ivermectin (IVM), an antiparasitic drug, for subcutaneous administration in dogs. The drug delivery system should: (i) ensure a full 12-month protection upon single dose administration; (ii) be safe with particular attention regarding IVM dosage and its release, in order to prevent over dosage side effects. This preliminary work involves: polymer selection, evaluation of the effects of γ-irradiation on the polymers and IVM, investigation and set up of suitable microparticle preparation process and parameters, IVM-loaded microparticles in vitro release evaluation. Results of gel permeation chromatography analysis on the irradiated polymers and IVM mixtures showed that combination of IVM with the antioxidant α-tocopherol (TCP) reduces the damage extent induced by irradiation treatment, independently on the polymer type. Solvent evaporation process was successfully used for the preparation of PLA microparticles and appropriately modified; it was recognized as suitable for the preparation of PCL microparticles. Good process yields were achieved ranging from 76.08% to 94.72%; encapsulation efficiency was between 85.76% and 91.25%, independently from the polymer used. The type of polymer and the consequent preparation process parameters affected microparticle size that was bigger for PCL microparticles (480-800 µm) and solvent residual that was >500 ppm for PLA microparticles. In vitro release test showed significantly faster IVM release rates from PCL microparticles, with respect to PLA microparticles, suggesting that a combination of the polymers could be used to obtain the suitable drug release rate. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted to investigate the biological effects of three distinct nanosized formulations with similar physical features, each composed of a precise Hyaluronic Acid molecular weight, in human bone marrow mesenchymal stem cells CD44+. Cytocompatibility and cell proliferation were assessed by MTT assay and Bromodeoxyuridine assay.

A novel formulation based on chondroitin sulphate/chitosan microspheres (CS/CH) has been investigated for oral delivery of macromolecules using ovalbumin as the model protein (OVA). The microspheres were prepared by a new emulsion-complex coacervation method. Physico-chemical properties of the polymers constituting microparticulate matrix were investigated by IR, DSC, TGA and X-ray diffraction analyses. In vitro tests were performed to evaluate the drug delivery system degradation and the protein release under conditions simulating the intestinal fluids. The ability of colonic enzymes to degrade the microparticulate systems was simulated employing the chondroitinase ABC enzyme. Results showed that the different CS/CH compositions influenced both microparticles stability and the protein release rate. Only the microspheres composed by 1:1 chondroitin sulphate–chitosan ratio achieved an OVA release profile suitable to a possible colon targeting. These microspheres released ∼30% of ovalbumin encapsulated in 24 h in the different aqueous media tested, while they released 100% of protein in the presence of chondroitinase. The preliminary results demonstrated that chondroitin sulphate-chitosan microspheres can be a suitable delivery system for protein drug envisaged to oral administration. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the surface modification of a natural bone substitute, Bio-Oss, coated with a synthetic polymer poly-D,L-lactide (PLA), in order to improve cell growth. Bio-Oss is a natural bone substitute made of the mineralized portion of bovine bone. The material is used mainly to fill bone defects in periodontal and maxillofacial surgery and permit reossification. Poly-a-hydroxyacids such as polylactic acid are receiving an increasing attention due to their ability to retain a great quantity of water, good biocompatibility, low interfacial tension, and minimal mechanical and frictional irritation. All of these features are appealing from the perspective of bioenvironmental mimicking. The human osteosarcoma cell line SAOS-2 was added to the top of scaffolds uncoated or coated with PLA and incubated at 37 degrees in 5% CO(2) for 15 days. PLA-coated scaffolds improved cell growth. Polymer degradation behaviour, extraction and measurement of the extracellular matrix proteins of the cultured scaffolds (such as decorin, fibronectin osteocalcin, osteonectin, osteopontin and type-I and type-III collagen), immunolocalization of bone proteins and morphological analysis of the scaffolds confirmed the bioactive properties of Bio-Oss/PLA4M suggesting that it could be a valuable grafting material. [ABSTRACT FROM AUTHOR]

In humans, injuries and diseases can result in irreversible tissue or organ loss. This well-known fact has prompted several basic studies on organisms capable of adult regeneration, such as amphibians, bony fish, and invertebrates. These studies have provided important biological information and helped to develop regenerative medicine therapies, but important gaps concerning the regulation of tissue and organ regeneration remain to be elucidated. To this aim, new models for studying regenerative biology could prove helpful. Here, the description of the cephalic tentacle regeneration in the adult of the freshwater snail Pomacea canaliculata is presented. In this invasive mollusk, the whole tentacle is reconstructed within 3 months. Regenerating epithelial, connective, muscular and neural components are already recognizable 72 h post-amputation (hpa). Only in the early phases of regeneration, several hemocytes are retrieved in the forming blastema. In view of quantifying the hemocytes retrieved in regenerating organs, granular hemocytes present in the tentacle blastema at 12 hpa were counted, with a new and specific computer-assisted image analysis protocol. Since it can be applied in absence of specific cell markers and after a common hematoxylin-eosin staining, this protocol could prove helpful to evidence and count the hemocytes interspersed among regenerating tissues, helping to unveil the role of immune-related cells in sensory organ regeneration. [ABSTRACT FROM AUTHOR]

Porous biodegradable scaffolds provide a physical substrate for cells allowing them to attach, proliferate and guide the formation of new tissues. A variety of techniques have been developed to fabricate tissue engineering (TE) scaffolds, among them the most relevant is the thermally-induced phase separation (TIPS). This technique has been widely used in recent years to fabricate three-dimensional (3D) TE scaffolds. Low production cost, simple experimental procedure and easy processability together with the capability to produce highly porous scaffolds with controllable architecture justify the popularity of TIPS. This paper provides a general overview of the TIPS methodology applied for the preparation of 3D porous TE scaffolds. The recent advances in the fabrication of porous scaffolds through this technique, in terms of technology and material selection, have been reviewed. In addition, how properties can be effectively modified to serve as ideal substrates for specific target cells has been specifically addressed. Additionally, examples are offered with respect to changes of TIPS procedure parameters, the combination of TIPS with other techniques and innovations in polymer or filler selection. [ABSTRACT FROM AUTHOR]

Supramolecular peptide hydrogels are gaining increased attention, owing to their potential in a variety of biomedical applications. Their physical properties are similar to those of the extracellular matrix (ECM), which is key to their applications in the cell culture of specialized cells, tissue engineering, skin regeneration, and wound healing. The structure of these hydrogels usually consists of a di- or tripeptide capped on the N-terminus with a hydrophobic aromatic group, such as Fmoc or naphthalene. Although these peptide conjugates can offer advantages over other types of gelators such as cross-linked polymers, they usually possess the limitation of being particularly sensitive to proteolysis by endogenous proteases. One of the strategies reported that can overcome this barrier is to use a peptidomimetic strategy, in which natural amino acids are switched for non-proteinogenic analogues, such as D-amino acids, β-amino acids, or dehydroamino acids. Such peptides usually possess much greater resistance to enzymatic hydrolysis. Peptides containing dehydroamino acids, i.e., dehydropeptides, are particularly interesting, as the presence of the double bond also introduces a conformational restraint to the peptide backbone, resulting in (often predictable) changes to the secondary structure of the peptide. This review focuses on peptide hydrogels and related nanostructures, where α,β-didehydro-α-amino acids have been successfully incorporated into the structure of peptide hydrogelators, and the resulting properties are discussed in terms of their potential biomedical applications. Where appropriate, their properties are compared with those of the corresponding peptide hydrogelator composed of canonical amino acids. In a wider context, we consider the presence of dehydroamino acids in natural compounds and medicinally important compounds as well as their limitations, and we consider some of the synthetic strategies for obtaining dehydropeptides. Finally, we consider the future direction for this research area. [ABSTRACT FROM AUTHOR]

Microfluidics is a relatively newly emerged field based on the combined principles of physics, chemistry, biology, fluid dynamics, microelectronics, and material science. Various materials can be processed into miniaturized chips containing channels and chambers in the microscale range. A diverse repertoire of methods can be chosen to manufacture such platforms of desired size, shape, and geometry. Whether they are used alone or in combination with other devices, microfluidic chips can be employed in nanoparticle preparation, drug encapsulation, delivery, and targeting, cell analysis, diagnosis, and cell culture. This paper presents microfluidic technology in terms of the available platform materials and fabrication techniques, also focusing on the biomedical applications of these remarkable devices. [ABSTRACT FROM AUTHOR]

The design, production, and characterisation of tissue-engineered scaffolds made of polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL) and their blends obtained through electrospinning (ES) or solvent casting/particulate leaching (SC) manufacturing techniques are presented here. The polymer blend composition was chosen to always obtain a prevalence of one of the two polymers, in order to investigate the contribution of the less concentrated polymer on the scaffolds' properties. Physical–chemical characterization of ES scaffolds demonstrated that tailoring of fibre diameter and Young modulus (YM) was possible by controlling PCL concentration in PLGA-based blends, increasing the fibre diameter from 0.6 to 1.0 µm and reducing the YM from about 22 to 9 MPa. SC scaffolds showed a "bubble-like" topography, caused by the porogen spherical particles, which is responsible for decreasing the contact angles from about 110° in ES scaffolds to about 74° in SC specimens. Nevertheless, due to phase separation within the blend, solvent-casted samples displayed less reproducible properties. Furthermore, ES samples were characterised by 10-fold higher water uptake than SC scaffolds. The scaffolds suitability as iPSCs culturing support was evaluated using XTT assay, and pluripotency and integrin gene expression were investigated using RT-PCR and RT-qPCR. Thanks to their higher wettability and appropriate YM, SC scaffolds seemed to be superior in ensuring high cell viability over 5 days, whereas the ability to maintain iPSCs pluripotency status was found to be similar for ES and SC scaffolds. [ABSTRACT FROM AUTHOR]

Hypertrophic scars (HTSs) are pathological structures resulting from chronic inflammation during the wound healing process, particularly in complex injuries like burns. The aim of this work is to propose Biofiber PF (biodegradable fiber loaded with Pirfenidone 1.5 w/w), an electrospun advanced dressing, as a solution for HTSs treatment in complex wounds. Biofiber has a 3-day antifibrotic action to modulate the fibrotic process and enhance physiological healing. Its electrospun structure consists of regular well-interconnected Poly-L-lactide-co-poly-ε-caprolactone (PLA-PCL) fibers (size 2.83 ± 0.46 µm) loaded with Pirfenidone (PF, 1.5% w/w), an antifibrotic agent. The textured matrix promotes the exudate balance through mild hydrophobic wettability behavior (109.3 ± 2.3°), and an appropriate equilibrium between the absorbency % (610.2 ± 171.54%) and the moisture vapor transmission rate (0.027 ± 0.036 g/min). Through its finer mechanical properties, Biofiber PF is conformable to the wound area, promoting movement and tissue oxygenation. These features also enhance the excellent elongation (>500%) and tenacity, both in dry and wet conditions. The ancillary antifibrotic action of PF on hypertrophic scar fibroblast (HSF) for 3 days downregulates the cell proliferation over time and modulates the gene expression of transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMA) at 48–72 h. After 6 days of treatment, a decrement of α-SMA protein levels was detected, proving the potential of biofiber as a valid therapeutic treatment for HTSs in an established wound healing process. [ABSTRACT FROM AUTHOR]

Background: To make the regenerative process more effective and efficient, tissue engineering (TE) strategies have been implemented. Three-dimensional scaffolds (electrospun or 3D-printed), due to their suitable designed architecture, offer the proper location of the position of cells, as well as cell adhesion and the deposition of the extracellular matrix. Moreover, the possibility to guarantee a concomitant release of drugs can promote tissue regeneration. Methods: A PLA/PCL copolymer was used for the manufacturing of electrospun and hybrid scaffolds (composed of a 3D-printed support coated with electrospun fibers). Dexamethasone was loaded as an anti-inflammatory drug into the electrospun fibers, and the drug release kinetics and scaffold biological behavior were evaluated. Results: The encapsulation efficiency (EE%) was higher than 80%. DXM embedding into the electrospun fibers resulted in a slowed drug release rate, and a slower release was seen in the hybrid scaffolds. The fibers maintained their nanometric dimensions (less than 800 nm) even after deposition on the 3D-printed supports. Cell adhesion and proliferation was favored in the DXM-loading hybrid scaffolds. Conclusions: The hybrid scaffolds that were developed in this study can be optimized as a versatile platform for soft tissue regeneration. [ABSTRACT FROM AUTHOR]

Chitosan is a natural polycationic polymer and due to its biocompatibility as well as bioactivity it is widely used for biomedical applications. Ferulic acid is a promising phenolic phytochemical with a wide range of biological activities such as antimicrobial and antioxidant properties. In this work, chitosan–bioactive glass–ferulic acid (CS-BG-FA) composite coatings were successfully fabricated using alternating current electrophoretic deposition (AC-EPD) technique. The morphology of the coatings was characterized by scanning electron microscopy (SEM) which showed a uniform composite layer of 140 μm in thickness. Chemical composition of the coatings was evaluated by using Fourier-transform infrared spectroscopy (FTIR) and Energy-dispersive X-ray spectroscopy (EDX). UV–Visible spectroscopy analysis confirmed the release of ferulic acid from the coatings. All samples exhibited a contact angle value in the range 41°–50°, which is in a suitable range for cell attachment and spreading. Moreover, the developed coatings formed a hydroxyapatite (HA) surface layer after 3 days of incubation in simulated body fluid (SBF), which was confirmed by SEM, EDX, FTIR, and XRD analyses. In vitro cell culture studies confirmed that the presence of ferulic acid in the coatings increased the viability of MG-63 human osteoblast-like cells. Furthermore, antibacterial tests showed that the presence of ferulic acid resulted in an effective bactericidal activity against gram–positive and gram−negative bacteria. • Ferulic acid as phenolic phytochemical incorporated in chitosan coatings • Electrophoretic deposition suitable for ferulic acid-chitosan-bioactive glass coatings • Release of ferulic acid from coatings leads to antibacterial effects. • Hydroxyapatite formed on coating surface after 3 days in simulated body fluid [ABSTRACT FROM AUTHOR]

Exogenous application of human epidermal growth factor (hEGF) stimulates epidermal wound healing. The aim of this study was to develop bioconjugates based on hEGF mimicking the protein in its native state and thus suitable for tissue engineering applications, in particular for treating skin-related disorders as burns. Ribonuclease A (RNase A) was used to investigate a number of different activated-agarose carriers: cyanogen bromide (CNBr)-activated-agarose and glyoxyl-agarose showed to preserve the appropriate orientation of the protein for receptor binding. EGF was immobilized on these carriers and immobilization yield was evaluated (100% and 12%, respectively). A peptide mapping of unbound protein regions was carried out by LC–MS to take evidence of the residues involved in the immobilization and, consequently, the flexibility and surface accessibility of immobilized EGF. To assess cell proliferative activities, 10, 25, 50, and 100 ng/mL of each immobilized EGF sample were seeded on fibroblast cells and incubated for 24, 48 and 72 h. The immobilized growth factor showed significantly high cell proliferative activity at 50 and 100 ng/mL compared to control and soluble EGF. Although both of the immobilized samples show dose-dependency when seeded with high number of fibroblast cells, CNBr-agarose-EGF showed a significantly high activity at 100 ng/mL and 72 h incubation, compared to glyoxyl-agarose-EGF. [ABSTRACT FROM AUTHOR]

Biocompatible thermosetting hydrogels are attractive compounds either for the delivery of drugs or as medical devices for tissue regeneration purposes. In this work Poly(Gamma-Glutamic Acid) (G-PGA) and G-PGA based hydrogels were explored. The hypothesis was to evaluate G-PGA and crosslinking agents combinations in order to obtain thermosetting hydrogels suitable for injection. Attention focused on hydrogels that can form by ionic interaction with compounds bearing amine groups, and/or by interaction with polymers such as chitosan and symmetric triblock copolymer (polyethylene glycol-polypropylene glycol- polyethylene glycol). Polymer solutions and related hydrogels characterization involved: rheologic behavior, osmolarity, syringeability and injectability. Results showed that G-PGA solutions syringeability was always acceptable, while injectability test did not meet aspiration by 22G needle. Osmolarity value suitable for injection could be obtain by adding buffering solutions. Only ternary blends made of chitosan, sodium beta-glyceroposphate and G-PGA, or G-PGA, Pluronic F68 and l -lysine, with fixed compositions, resulted in thermosetting gels. The obtained thermosetting gels were not reversible. [ABSTRACT FROM AUTHOR]

Potential off-label therapeutic role of N-acetylcysteine (N-Ac) was recently demonstrated in the treatment of diastrophic dysplasia (DTD) using mutant mice; its main drawback is the rapid clearance from blood due to the liver metabolism. Our goal was to investigate the potential of polyethylene glycol polylactide-co-glycolide block copolymer (PLGA-PEG)–based nanoparticles (NPs) in order to improve in vivo biodistribution performances and N-Ac pharmacokinetic profile after subcutaneous administration in mice. Results suggest that N-Ac can be effectively loaded into NPs (about 99 μg/mg NPs) using a suitably optimized nanoprecipitation method. Thanks to the good physical characteristics (mean diameter <100 nm, zeta potential about −8 mV) NPs can reach skeletal tissue in particular femoral head and proximal tibia epiphysis at the sixth hour after injection, remaining in the tissues till 24 h. Furthermore, pharmacokinetic study revealed a sustained N-Ac concentration in plasma with a peak concentration of 2.48 ± 1.72 μM at the 24th hour after injection. Overall, results highlight the actual interest of N-Ac-loaded PLGA-PEG NPs as useful platform for N-Ac parenteral administration. [ABSTRACT FROM AUTHOR]

[Display omitted] By carefully controlling the dose administered and the drug release rate from drug-eluting implants, safety and efficacy of the therapeutic agent dispensed can be improved. The present work focuses on the promising advantages of 3D Bioprinting process in developing two layers' implantable scaffolds. The two layers have different functions, in order to ensure a more effective and synergistic breast cancer therapy. First layer involves use of polymers such as Poly- ε-Caprolactone (PCL) and Chitosan (CS), and incorporation of 5-Fluorouracil (5-FU). The aim of the first layer is releasing the drug within 4 weeks, obtaining a prolonged and modified release. According to in vitro drug release tests performed, ∼32 % of 5-FU was released after one month, after an initial burst effect of 17.22 %. The sudden release of the drug into the body would quickly reach an effective therapeutic concentration, while the drug sustained release maintains an effective therapeutic concentration range during the administration time. The second layer is made exclusively from PCL as polymeric matrix, into which Gold Nanoparticles (AuNPs) were subsequently loaded, and its main purpose is to be radiation enhancement. The long biodegradation time of PCL would make the non-soluble scaffold an alternative to conventional chemotherapy, optimizing drug release to the specific needs of the patients. [ABSTRACT FROM AUTHOR]

[Display omitted] Nanomedicine consists in the application of nanotechnology in medicine to revolutionize the healthcare sector through transformative new diagnostic and therapeutic tools. In this field, nanostructures or nanocarriers (i.e., nanoparticles) are extensively used as a drug delivery system. Despite the well-defined profits offered by nanomedicines based on poly (lactic- co -glycolic acid) (PLGA), the major barriers hampering the launch of a nanoparticles-based product on the market are batch-to-batch variations and its lack of reproducibility from the benchtop to an industrial scale production. Currently, microfluidics technology has emerged as potential tool to achieve a continuous manufacturing with a precise control over fluids mixing and particles quality attributes. This work aims at defining a tailored strategy to produce PLGA NPs, exploiting a new microfluidic device. Moreover, Design of Experiments (DoE) and computational fluid dynamics approaches were exploited to understand the main process parameters and material attributes affecting the quality of the final product as well as the NPs manufacturing process. Finally, the ability to incorporate a drug into the PLGA nanoparticles was investigated by using Curcumin as model payload reaching encapsulation efficiency in the rank 28–44%. This paper is proposed as useful guide for the preparation of PLGA NPs by microfluidic technique. [ABSTRACT FROM AUTHOR]

[Display omitted] • Textured fibrous dressings, bead-free and with uniform fibers, are fabricated by electrospinning method. • Textured fibrous dressings facilitate vertical exudate absorption and have optimal moisture vapor transmission rate. • The round texture is ideal for flat surfaces that tend to deform linearly, such as the shoulders, neck, and hips. • Cells proliferates on textured fiber dressing, with the extent of proliferation as a function of incubation time. Biofiber is a new generation of highly absorbent, and textured bandage with patented fiber technology. Biofiber has a sophisticated texture that provides an optimum balance of moisture, flexibility, and conformability, and it has been developed with specific properties to treat complex injuries like burns. The dressing has been designed to be completely adaptable to human anatomy, and it can be fitted to any part of the body, adapting to all curves and jointures, as well as fitting the facial features. Prototypes of PLA-PCL-based textured bandages were developed by electrospinning, characterized, and evaluated for complex wound care. The texture is both esthetic and functional; fibers were uniformly sized (2.2 ± 0.8 and 4.5 ± 0.3 µm) and well interconnected. The texture facilitates vertical absorption of exudate up to 2.5 g/g of bandage, and the high contact angle values (120 – 100°) create an optimum balance of moisture for the healing process. The textured prototypes turned out to be extremely stable; no sign of bandage debris was found by the standard test, BS EN 13726–1.7. In addition, the round texture (3R) showed improvements in tensile strength (0.27 ± 0.019 MPa), ultimate tensile strength (0.83 ± 0.05 MPa) with higher breaking point (0.91 ± 0.05 MPa) compared to control (Mepilex Lite®). The amount of albumin (BSA) and Fibrinogen (Fb) adhered on textured fiber prototypes was calculated by BCA Assay, all prototypes demonstrated strong BSA (ranging from 81.66 ± 8.93 to 182.73 ± 2.07 μg protein/mg dressing) and enhanced Fb shielding (ranging from 108.25 ± 7.3 to 238.12 ± 17.76 μg protein/mg dressing). Their MVTR values ranged from 2313.27 ± 58.86 to 2603.33 ± 50.41 g/m2· day and vertical wicking heights were between 24.6 ± 2.5 and 29.3 ± 4.1 mm; biological tests demonstrated good compatibility of prototypes (cell vitality > 70 %), percentage of cells attachment was in-between 114 and 225 %. The extent of attachment depends on texture, differing topographical patterns presented higher attachment compared with both CTR + and 1P prototype (no texture). Cells were growth on textured fiber prototypes, and the extent of proliferation depend on incubation time. [ABSTRACT FROM AUTHOR]

Neural tube defects (NTDs) represent the second most common cause of congenital malformations in the children. Aim of the work is the development of a shape memory engineered scaffold (SMES) focused to potentially improve Myelomeningocele (most common type of spina bifida defect) repair in fetus. Copolymer poly- l -lactide- co -ε-caprolactone (PLA-PCL) 70:30 M ratio, due to its glass transition temperature (Tg°) close to physiologic temperature (32–42 °C) was used to produce electrospun scaffolds that were engineered with MSCs from amniotic fluid. The engineered scaffolds were rolled up and then underwent a cycle of high (T° > Tg°) and low temperature (T° < Tg°) in order to induce solid status change from rubbery to glassy and fix their rolled shape. The scaffolds were characterized for the shape memory parameters Rf% (ability to fix new temperature induced shape) and Rr% (ability to recover the primary shape). Biological characterization included cell viability % determination by MTT test, cytofluorimetry and microscope analysis for DAPI stained and Live-Dead Assay. Scaffold degradation test was performed in amniotic fluid and mechanical properties of electrospun scaffold were evaluated up to 4 months incubation in amniotic fluid simulated in vivo conditions. The preliminary and innovative results obtained from this work permit to consider this SMES a good shape memory material (Rf% =79 ± 5.2; Rr% = 98 ± 3.1) and suitable support for MSCs proliferation. [Display omitted] • Shape memory is an inherent property of some polymers. • PLA-PCL has temperature induced shape memory properties. • PLA-PCL shape memory electrospun scaffolds were engineered with mesenchymal stem cells (MSCs). • Shape memory engineered scaffolds (SMESs) were evaluated for Tissue Engineered Application. • SMES provide minimal invasive surgery through fetoscopy. • SMES provide a local and stable cell source favoring new tissue formation. • Biodegradable and biocompatible SMES don't require a following surgical operation for scaffold removal. [ABSTRACT FROM AUTHOR]

Oral immunization offers a minimally invasive administration, inducing local and systemic immune responses and facilitating mass immunization without needle-related risks. However, the gastrointestinal environment poses challenges, compromising vaccine effectiveness through enzymatic degradation and poor absorption by Peyer's patches. Advances in nanoparticle and microparticle (NP/MP) technology protect vaccines from degradation and enhance targeted release. The aim of this study was to develop pH-controlled polymeric carriers for the oral delivery of protein vaccines in order to target the antigen-presenting cells and M cells in the region of Peyer's patches. Here, myoglobin was chosen as a model protein vaccine. This study focuses on Eudragit L100, a pH-responsive polymer stable in acidic conditions and dissolving at higher pH, to develop carriers for controlled myoglobin release in the intestinal tract. A microfluidic-based manufacturing process for Eudragit L100 NPs and MPs is optimized using a comprehensive experimental and computational approach to obtain NPs and MPs through the same setup. Integrating in silico and experimental methods highlights the potential of numerical simulations to streamline final product development. This approach improves the efficiency and cost-effectiveness of NP/MP production, demonstrating how the combination of design of experiment and numerical simulations can optimize production parameters and refine manufacturing processes for advanced drug delivery systems.

In the last few years, the microfluidic production of nanoparticles (NPs) is becoming a promising alternative to conventional industrial approaches (e.g., nanoprecipitation, salting out, and emulsification-diffusion) thanks to the production efficiency, low variability, and high controllability of the production parameters. Nevertheless, the development of new formulations and the switching of the production process toward microfluidic platforms requires expensive and time-consuming number of experiments for the tuning of the formulation to obtain NPs with specific morphological and functional characteristics. In this work, we developed a computational fluid dynamic pipeline, validated through an ad hoc experimental strategy, to reproduce the mixing between the solvent and anti-solvent (i.e., acetonitrile and TRIS-HCl, respectively). Moreover, beyond the classical variables able to describe the mixing performances of the microfluidic chip, novel variables were described in order to assess the region of the NPs formation and the changing of the amplitude of the precipitation region according to different hydraulic conditions. The numerical approach proved to be able to capture a progressive reduction of the nanoprecipitation region due to an increment of the flow rate ratio; in parallel, through the experimental production, a progressive increment of the NPs size heterogeneity was observed with the same fluid dynamic conditions. Hence, the preliminary comparison between numerical and experimental evidence proved the effectiveness of the computational strategy to optimize the NPs manufacturing process., Competing Interests: Declarations Conflict of interest There are no conflicts to declare., (© 2024. The Author(s).)

The fight against infectious disease has remained an ever-evolving challenge in the landscape of healthcare. The ability of pathogens to develop resistance against conventional drug treatments has decreased the effectiveness of therapeutic interventions, and antibiotic resistance is recognized as one of the main challenges of our time. The goal of this systematic review paper is to provide insight into the research papers published on innovative nanosized drug delivery systems (DDSs) based on gentamycin and vancomycin and to discuss the opportunity of their repurposing through nano DDS formulations. These two antibiotics are selected because (i) gentamicin is the first-line drug used to treat suspected or confirmed infections caused by Gram-negative bacterial infections and (ii) vancomycin is used to treat serious Gram-positive bacterial infections. Moreover, both antibiotics have severe adverse effects, and one of the purposes of their formulation as nanosized DDSs is to overcome them. The review paper includes an introduction focusing on the challenges of infectious diseases and traditional therapeutic treatments, a brief description of the chemical and pharmacological properties of gentamicin and vancomycin, case studies from the literature on innovative nanosized DDSs as carriers of the two antibiotic drugs, and a discussion of the results found in the literature.

Poly (glycerol sebacate) is a widely studied elastomeric copolymer obtained from the polycondensation of two bioresorbable monomers, glycerol and sebacic acid. Due to its biocompatibility and the possibility to tailor its biodegradability rate and mechanical properties, PGS has gained lots of interest in the last two decades, especially in the soft tissue engineering field. Different synthetic approaches have been proposed, ranging from classic thermal polyesterification and curing to microwave-assisted organic synthesis, UV crosslinking and enzymatic catalysis. Each technique, characterized by its advantages and disadvantages, can be tailored by controlling the crosslinking density, which depends on specific synthetic parameters. In this work, classic and alternative synthetic methods, as well as characterisation and tailoring techniques, are critically reviewed with the aim to provide a valuable tool for the reproducible and customized production of PGS for tissue engineering applications.

Lipid-based nanocarriers have emerged as helpful tools to deliver sensible biomolecules such as proteins and oligonucleotides. To have a fast and robust microfluidic-based nanoparticle synthesis method, the setup of versatile equipment should allow for the rapid transfer to scale cost-effectively while ensuring tunable, precise and reproducible nanoparticle attributes. The present work aims to assess the effect of different micromixer geometries on the manufacturing of lipid nanocarriers taking into account the influence on the mixing efficiency by changing the fluid-fluid interface and indeed the mass transfer. Since the geometry of the adopted micromixer varies from those already published, a Design of Experiment (DoE) was necessary to identify the operating (total flow, flow rate ratio) and formulation (lipid concentration, lipid molar ratios) parameters affecting the nanocarrier quality. The suitable application of the platform was investigated by producing neutral, stealth and cationic liposomes, using DaunoXome ® , Myocet ® , Onivyde ® and Onpattro ® as the benchmark. The effect of condensing lipid (DOTAP, 3-10-20 mol%), coating lipids (DSPE-PEG550 and DSPE-PEG2000), as well as structural lipids (DSPC, eggPC) was pointed out. A very satisfactory encapsulation efficiency, always higher than 70%, was successfully obtained for model biomolecules (myoglobin, short and long nucleic acids).

Bioprinting offers new opportunities to obtain reliable 3D in vitro models of the liver for testing new drugs and studying pathophysiological mechanisms, thanks to its main feature in controlling the spatial deposition of cell-laden hydrogels. In this context, decellularized extracellular matrix (dECM)-based hydrogels have caught more and more attention over the last years because of their characteristic to closely mimic the tissue-specific microenvironment from a biological point of view. In this work, we describe a new concept of designing dECM-based hydrogels; in particular, we set up an alternative and more practical protocol to develop a hepatic lyophilized dECM (lyo-dECM) powder as an 'off-the-shelf' and free soluble product to be incorporated as a biomimetic component in the design of 3D-printable hybrid hydrogels. To this aim, the powder was first characterized in terms of cytocompatibility on human and porcine mesenchymal stem cells (MSCs), and the optimal powder concentration (i.e. 3.75 mg ml -1 ) to use in the hydrogel formulation was identified. Moreover, its non-immunogenicity and capacity to reactivate the elastase enzyme potency was proved. Afterward, as a proof-of-concept, the powder was added to a sodium alginate/gelatin blend, and the so-defined multi-component hydrogel was studied from a rheological point of view, demonstrating that adding the lyo-dECM powder at the selected concentration did not alter the viscoelastic properties of the original material. Then, a printing assessment was performed with the support of computational simulations, which were useful to define a priori the hydrogel printing parameters as window of printability and its post-printing mechanical collapse. Finally, the proposed multi-component hydrogel was bioprinted with cells inside, and its post-printing cell viability for up to 7 d was successfully demonstrated., (Creative Commons Attribution license.)

3D printing has provided a new prospective in the manufacturing of personalized medical implants, including fistulas for haemodialysis (HD). In the current study, an optimized fused modelling deposition (FDM) 3D printing method has been validated, for the first time, to obtain cylindrical shaped fistulas. Printing parameters were evaluated for the manufacturing of fistulas using blank and 0.25% curcumin-loaded filaments that were produced by hot melt extrusion (HME). Four different fistula types have been designed and characterized using a variety of physicochemical characterization methods. Each design was printed three times to demonstrate printing process accuracy considering outer and inner diameter, wall thickness, width, and length. A thermoplastic polyurethane (TPU) biocompatible elastomer was chosen, showing good mechanical properties with a high elastic modulus and maximum elongation, as well as stability at high temperatures with less than 0.8% of degradation at the range between 25 and 250 °C. Curcumin release profile has been evaluated in a saline buffer, obtaining a low release (12%) and demonstrating drug could continue release for a longer period, and for as long as grafts should remain in patient body. Possibility to produce drug-loaded grafts using one-step method as well as 3D printing process and TPU filaments containing curcumin printability has been demonstrated., (© 2021. The Author(s).)

This study is a proof of concept performed to evaluate process parameters affecting shape memory effect of copolymer poly-L-lactide-co-poly-ε-caprolactone (PLA:PCL) 70:30 ratio based nanofibrous scaffolds. A design of experiment (DOE) statistical approach was used to define the interaction between independent material and process variables related to electrospun scaffold manufacturing, such as polymer solution concentration (w/v%), spinning time (min), and needle size (Gauge), and their influence on Rf% (ability of the scaffold to maintain the induced temporary shape) and Rr% (ability of the scaffold to recover its original shape) outputs. A mathematical model was obtained from DOE useful to predict scaffold Rf% and Rr% values. PLA-PCL 15% w/v, 22G needle, and 20-min spinning time were selected to confirm the data obtained from theoretical model. Subsequent morphological (SEM), chemical-physical (GPC and DSC), mechanical (uniaxial tensile tests), and biological (cell viability and adhesion) characterizations were performed., (© 2022. The Author(s).)