Polycaprolactone Scaffolds Fabricated via Bioextrusion for Tissue Engineering Applications

The most promising approach in Tissue Engineering involves the seeding of porous, biocompatible/biodegradable scaffolds, with donor cells to promote tissue regeneration. Additive biomanufacturing processes are increasingly recognized as ideal techniques to produce 3D structures with optimal pore size and spatial distribution, providing an adequate mechanical support for tissue regeneration while shaping in-growing tissues. This paper presents a novel extrusion-based system to produce 3D scaffolds with controlled internal/external geometry for TE applications.The BioExtruder is a low-cost system that uses a proper fabrication code based on the ISO programming language enabling the fabrication of multimaterial scaffolds. Poly(ε-caprolactone) was the material chosen to produce porous scaffolds, made by layers of directionally aligned microfilaments. Chemical, morphological, and in vitro biological evaluation performed on the polymeric constructs revealed a high potential of the BioExtruder to produce 3D scaffolds with regular and reproducible macropore architecture, without inducing relevant chemical and biocompatibility alterations of the material

Insight into halloysite nanotubes-loaded gellan gum hydrogels for soft tissue engineering applications

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Cell-based medicinal products approved in the European Union: current evidence and perspectives

Advanced Therapy Medicinal Products (ATMPs) are innovative clinical treatments exploiting the pharmacological, immunological, or metabolic properties of cells and/or gene(s) with the aim to restore, correct, or modify a biological function in the recipient. ATMPs are heterogeneous medicinal products, developed mainly as individualized and patient-specific treatments, and represent new opportunities for diseases characterized by a high-unmet medical need, including rare, genetic and neurodegenerative disorders, haematological malignancies, cancer, autoimmune, inflammatory and orthopaedic conditions. Into the European Union (EU) market, the first ATMP has been launched in 2009 and, to date, a total of 24 ATMPs have been approved. This review aims at reporting on current evidence of cell-based therapies authorized in the EU, including Somatic Cell Therapies, Tissue Engineering Products, and Cell-based Gene Therapy Products as Chimeric Antigen Receptor (CAR) T-cells, focusing on the evaluation of efficacy and safety in clinical trials and real-world settings. Despite cell-based therapy representing a substantial promise for patients with very limited treatment options, some limitations for its widespread use in the clinical setting remain, including restricted indications, highly complex manufacturing processes, elevated production costs, the lability of cellular products over time, and the potential safety concerns related to the intrinsic characteristics of living cells, including the risk of severe or life-threatening toxicities, such as CAR-T induced neurotoxicity and cytokine release syndrome (CRS). Although encouraging findings support the clinical use of ATMPs, additional data, comparative studies with a long-term follow-up, and wider real-world evidences are needed to provide further insights into their efficacy and safety profiles

Preliminary survey on the occurrence of microplastics in bivalve mollusks marketed in Apulian fish markets

Microplastics (MPs) are a relevant threat to food safety because they are ingested by humans through various foods. Bivalves are at high risk of microplastic contamination due to their filter-feeding mechanism and pose a risk to consumers as they are ingested whole. In this work, microplastics were detected, quantified, identified, and classified in samples of mussels (Mytilus galloprovincialis) and oysters (Crassostrea gigas) marketed in the Apulia region. The total number of plastic debris was 789 particles in the mussel samples and 270 particles in the oyster samples, with size ranging from 10 to 7350 µm. Fragments with size within the category of 5-500 µm were the predominant findings in both species, with blue as the predominant color in mussels and transparent in oysters; most of the debris was polyamide and nylon polymers in the mussels and chlorinated polypropylene in the oysters. These results show that mussel and oyster samples purchased at fish markets are contaminated with microplastics. The sources may be diverse and further studies are needed to assess the impact of the marketing stage on microplastic contamination in bivalves to better define the human risk assessment associated with microplastic exposure from bivalves consumption

Simulating bacteria-materials interactions via agent-based modeling

This work reports the outcomes of in silico simulations of the interactions between S. aureus bacteria and an antibacterial polymeric coating developed onto titanium substrates. The aim of the theoretical analysis is to develop a computational approach suitable of predicting the effective amount of antibacterial agents to load onto the polymeric coating in order to prevent titanium implants infections and at the same time to minimize cytotoxicity. The simulations results will be contrasted with experimental data

Multiblock Polyurethanes Based on Biodegradable Amphiphilic Poly(ε-caprolactone)/Poly(ethylene glycol) Segments as Candidates for Tissue Engineering Applications

Biodegradable amphiphilic multiblock poly(ether-ester-urethane)s were prepared by one-step bulk polycondensation of PEG and PCL macrodiols and HMDI with good yields and high molecular weights. The copolymers were characterized by 1H-NMR, FT-IR, SEC, TGA and DSC analysis. Different ratios of PEG/PCL, PEG macromonomer length and copolymer molecular weights allowed for tuning their hydrophilicity. Thanks to their tunable characteristics, the prepared multiblock copolymers can be exploited in the fabrication of biodegradable scaffolds for tissue engineering by means of the electrospinning technique

Surface Characterization of Electro-Assisted Titanium Implants: A Multi-Technique Approach

The understanding of chemical–physical, morphological, and mechanical properties of polymer coatings is a crucial preliminary step for further biological evaluation of the processes occurring on the coatings’ surface. Several studies have demonstrated how surface properties play a key role in the interactions between biomolecules (e.g., proteins, cells, extracellular matrix, and biological fluids) and titanium, such as chemical composition (investigated by means of XPS, TOF-SIMS, and ATR-FTIR), morphology (SEM–EDX), roughness (AFM), thickness (Ellipsometry), wettability (CA), solution–surface interactions (QCM-D), and mechanical features (hardness, elastic modulus, adhesion, and fatigue strength). In this review, we report an overview of the main analytical and mechanical methods commonly used to characterize polymer-based coatings deposited on titanium implants by electro-assisted techniques. A description of the relevance and shortcomings of each technique is described, in order to provide suitable information for the design and characterization of advanced coatings or for the optimization of the existing ones

Electrochemical Strategies for Titanium Implant Polymeric Coatings: The Why and How

Among the several strategies aimed at polymeric coatings deposition on titanium (Ti) and its alloys, metals commonly used in orthopaedic and orthodontic prosthesis, electrochemical approaches have gained growing interest, thanks to their high versatility. In this review, we will present two main electrochemical procedures to obtain stable, low cost and reliable polymeric coatings: electrochemical polymerization and electrophoretic deposition. Distinction should be made between bioinert films—having mainly the purpose of hindering corrosive processes of the underlying metal—and bioactive films—capable of improving biological compatibility, avoiding inflammation or implant-associated infection processes, and so forth. However, very often, these two objectives have been pursued and achieved contemporaneously. Indeed, the ideal coating is a system in which anti-corrosion, anti-infection and osseointegration can be obtained simultaneously. The ultimate goal of all these coatings is the better control of properties and processes occurring at the titanium interface, with a special emphasis on the cell-coating interactions. Finally, advantages and drawbacks of these electrochemical strategies have been highlighted in the concluding remarks

A 3D Printed Composite Scaffold Loaded with Clodronate to Regenerate Osteoporotic Bone:In Vitro Characterization

Additive manufacturing (AM) is changing our current approach to the clinical treatment of bone diseases, providing new opportunities to fabricate customized, complex 3D structures with bioactive materials. Among several AM techniques, the BioCell Printing is an advanced, integrated system for material manufacture, sterilization, direct cell seeding and growth, which allows for the production of high-resolution micro-architectures. This work proposes the use of the BioCell Printing to fabricate polymer-based scaffolds reinforced with ceramics and loaded with bisphosphonates for the treatment of osteoporotic bone fractures. In particular, biodegradable poly(epsilon-caprolactone) was blended with hydroxyapatite particles and clodronate, a bisphosphonate with known efficacy against several bone diseases. The scaffolds' morphology was investigated by means of Scanning Electron Microscopy (SEM) and micro-Computed Tomography (micro-CT) while Energy Dispersive X-ray Spectroscopy (EDX) and X-ray Photoelectron Spectroscopy (XPS) revealed the scaffolds' elemental composition. A thermal characterization of the composites was accomplished by Thermogravimetric analyses (TGA). The mechanical performance of printed scaffolds was investigated under static compression and compared against that of native human bone. The designed 3D scaffolds promoted the attachment and proliferation of human MSCs. In addition, the presence of clodronate supported cell differentiation, as demonstrated by the normalized alkaline phosphatase activity. The obtained results show that the BioCell Printing can easily be employed to generate 3D constructs with pre-defined internal/external shapes capable of acting as a temporary physical template for regeneration of cancellous bone tissues