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Background: Clay minerals are nanomaterials that have recently been recognized as enabling excipients that can promote cell adhesion, proliferation, and differentiation. When nanoclays are loaded in a 3D polymeric nanostructure, the cell-substrate interaction is enhanced, and other bioactive properties are optimized., Purpose: In this study, hectorite (HEC)- and montmorillonite (MMT)-doped polymeric scaffolds were explored for the treatment of deep and chronic skin lesions., Methods: Scaffolds were manufactured by means of electrospinning and then crosslinked by heating. Physicochemical analyses were correlated with in vitro biopharmaceutical characterization to predict the in vivo fate of the clay-doped scaffolds., Results and Discussion: The addition of MMT or HEC to the polymeric scaffold framework modifies the surface arrangement and, consequently, the potential of the scaffolds to interact with biological proteins. The presence of nanoclays alters the nanofiber morphology and size, and MMT doping increases wettability and protein adhesion. This has an impact on fibroblast behavior in a shorter time since scaffold stiffness facilitates cell adhesion and cell proliferation., Conclusion: MMT proved to perform better than HEC, and this could be related to its higher hydrophilicity and protein adhesion., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Miele et al.)

Tendon disorders are common medical conditions that could lead to significant disability, pain, healthcare costs, and a loss of productivity. Traditional approaches require long periods of treatment, and they largely fail due to the tissues weakening and the postoperative alterations of the normal joint mechanics. To overcome these limitations, innovative strategies for the treatment of these injuries need to be explored. The aim of the present work was the design of nano-fibrous scaffolds based on poly(butyl cyanoacrylate) (PBCA), a well-known biodegradable and biocompatible synthetic polymer, doped with copper oxide nanoparticles and caseinphosphopeptides (CPP), able to mimic the hierarchical structure of the tendon and to improve the tissue healing potential. These were developed as implants to be sutured to reconstruct the tendons and the ligaments during surgery. PBCA was synthetized, and then electrospun to produce aligned nanofibers. The obtained scaffolds were characterized for their structure and physico-chemical and mechanical properties, highlighting that CuO and CPP loading, and the aligned conformation determined an increase in the scaffold mechanical performance. Furthermore, the scaffolds loaded with CuO showed antioxidant and anti-inflammatory properties. Moreover, human tenocytes adhesion and proliferation to the scaffolds were assessed in vitro. Finally, the antibacterial activity of the scaffolds was evaluated using Escherichia coli and Staphylococcus aureus as representative of Gram-negative and Gram-positive bacteria, respectively, demonstrating that the CuO-doped scaffolds possessed a significant antimicrobial effect against E. coli . In conclusion, scaffolds based on PBCA and doped with CuO and CPP deserve particular attention as enhancers of the tendon tissue regeneration and able to avoid bacterial adhesion. Further investigation on the scaffold efficacy in vivo will assess their capability for enhancing the tendon ECM restoration in view of accelerating their translation to the clinic.

Purpose: Aim of the work was to develop a potential neural scaffold, endowed with neuroprotective and neuroregenerative potential, to be applied at the site of nervous tissue injuries: nanofibers, consisting of gellan gum (GG), spermidine (SP) and gelatin (GL), were prepared via electrospinning. SP was selected for its neuroprotective activity and cationic nature that makes it an ideal GG cross-linking agent. GL was added to improve the scaffold bioactivity., Methods: Mixtures, containing 1.5% w/w GG and increasing SP concentrations (0-0.125% w/w), were prepared to investigate GG/SP interaction and, thus, to find the best mixture to be electrospun. Mixture rheological and mechanical properties were assessed. The addition of 0.1% w/w GL was also investigated. The most promising GG/SP/GL mixtures were added with poly(ethylene oxide) (PEO) and poloxamer (P407) and, then, electrospun. The resulting fibers were characterized in terms of size and mechanical properties and fiber morphology was observed after soaking in water for 24 hours. Nanofiber biocompatibility was assessed on Schwann cells., Results: More and more structured GG/SP mixtures were obtained by increasing SP concentration, proving its cross-linking potential. After blending with PEO and P407, the mixture consisting of 1.5% w/w GG, 0.05% w/w SP and 0.1% w/w GL was electrospun. The resulting nanofibers appeared homogenous and characterized by a plastic behavior, suggesting a good mechanical resistance when applied at the injury site. Nanofibers were insoluble in aqueous media and able to form a thin gel layer after hydration. GG/SP/GL nanofibers showed a higher compatibility with Schwann cells than GG/SP ones., Conclusion: SP and GL allowed the production of homogenous GG-based nanofibers, which preserved their structure after contact with aqueous media and showed a good compatibility with a neural cell line. After local application at the injury site, nanofibers should support and guide axonal outgrowth, releasing SP in a controlled manner., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Vigani et al.)

The present work proposed a novel therapeutic platform with both neuroprotective and neuroregenerative potential to be used in the treatment of spinal cord injury (SCI). A dual-functioning scaffold for the delivery of the neuroprotective S1R agonist, RC-33, to be locally implanted at the site of SCI, was developed. RC-33-loaded fibers, containing alginate (ALG) and a mixture of two different grades of poly(ethylene oxide) (PEO), were prepared by electrospinning. After ionotropic cross-linking, fibers were incorporated in chitosan (CS) films to obtain a drug delivery system more flexible, easier to handle, and characterized by a controlled degradation rate. Dialysis equilibrium studies demonstrated that ALG was able to form an interaction product with the cationic RC-33 and to control RC-33 release in the physiological medium. Fibers loaded with RC-33 at the concentration corresponding to 10% of ALG maximum binding capacity were incorporated in films based on CS at two different molecular weights-low (CSL) and medium (CSM)-solubilized in acetic (AA) or glutamic (GA) acid. CSL- based scaffolds were subjected to a degradation test in order to investigate if the different CSL salification could affect the film behavior when in contact with media that mimic SCI environment. CSL AA exhibited a slower biodegradation and a good compatibility towards human neuroblastoma cell line.

In healthy individuals, wound healing is a highly efficient process. However, interruptions of normal healing give rise to chronic wounds, characterized by inflammation with impaired angiogenesis and re-epithelialization. The aim of this work was the design and the development of electrospun nanofibrous scaffolds based on sodium alginate (SA) and pullulan (PUL) and loaded with human platelet lysate (PL) intended for skin reparation, to take the advantage of nanofibrous scaffolds (with improved physical structure) and of SA as biopolymer. Two preparation approaches have been used to load PL in the scaffolds: as component of the PUL/SA matrix, to be electrospun, or as coating component, to cover the previously prepared electrospun PUL based membranes. A preformulation study to assess pullulan entanglement concentration and alginate or citric acid critical concentration, to obtain electrospun nanofibers, has been performed. The preparation process allowed to obtain insoluble systems starting from aqueous solutions and these were able to act as scaffolds for tissue engineering with suitable mechanical properties and PL release. PL loading in PUL/SA matrix nanofibers did not substantially modify the nanofiber morphology before crosslinking, while the crosslinking process, in presence of PL, determined less sharp nanofibers probably due to an increase in hydrophilicity caused by PL proteins. On the contrary, the coated nanofibers showed an increase in diameters due to PL loading. The two different approaches affected the fiber dimension and scaffold elasticity, especially for PL loaded systems. Anyhow, these differences were not crucial for fibroblast adhesion and proliferation which were mainly influenced by PL loading. In particular, fibroblasts presented different conformation and orientation mainly due to the presence of PL. This caused a cell random orientation compatible to a fibroblast-to-myofibroblast transition that could enhance wound healing., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: The aim of the present work was to develop biodegradable alginate (ALG)-containing fibrous membranes intended for tissue repair, acting as both drug delivery systems and cell growth guidance., Methods: Membranes were prepared by electrospinning. Since ALG can be electrospun only when blended with other spinnable polymers, dextran (DEX) and polyethylene oxide (PEO) were investigated as process adjuvants. ALG/DEX mixtures, characterized by different rheological and conductivity properties, were prepared in phosphate buffer or deionized water; surfactants were added to modulate polymer solution surface tension. The Design of Experiments (DoE) approach (full factorial design) was used to investigate the role of polymer solution features (rheological properties, surface tension, and conductivity) on electrospun fiber morphology. A high viscosity at 1,000 s -1 (1.3-1.9 Pa.s) or a high pseudoplasticity index (≥1.7), combined with a low surface tension (30-32 mN/m) and a low conductivity (800-1,000 μS/cm), was responsible for the production of ALG/DEX homogeneous fibers. Such ranges were successfully employed for the preparation of ALG-containing fibers, using PEO, instead of DEX, as process adjuvant. ALG/DEX and ALG/PEO fibers were subsequently subjected to cross-linking/coating processes to make them slowly biodegradable in aqueous medium. In particular, ALG/PEO fibers were cross-linked and coated with CaCl 2 /chitosan solutions in water/ethanol mixtures. Due to DEX high content, ALG/DEX fibers were soaked in a polylactide-co-glycolide (PLGA) solution in ethyl acetate., Results: Both cross-linking and coating processes made fibers insoluble in physiological medium and produced an increase in their mechanical resistance, assessed by means of a tensile test. PLGA-coated ALG/DEX and chitosan-coated ALG/PEO fibers were biocompatible and able to support fibroblast adhesion., Conclusion: The DoE approach allowed to draw up guidelines useful for the preparation of homogeneous fibers, starting from mixtures of ALG and non-ionic polymers. Such fibers, upon coating, resulted to be good cell substrates, allowing cell adhesion and growth., Competing Interests: Disclosure The authors report no conflicts of interest in this work.