Additive manufacturing (AM) techniques have gained interest in the tissue engineering field, thanks to their versatility and unique possibilities of producing constructs with complex macroscopic geometries and defined patterns. Recently, composite materials-namely, heterogeneous biomaterials identified as continuous phase (matrix) and reinforcement (filler)-have been proposed as inks that can be processed by AM to obtain scaffolds with improved biomimetic and bioactive properties. Significant efforts have been dedicated to hydroxyapatite (HA)-reinforced composites, especially targeting bone tissue engineering, thanks to the chemical similarities of HA with respect to mineral components of native mineralized tissues. Herein, applications of AM techniques to process HA-reinforced composites and biocomposites for the production of scaffolds with biological matrices, including cellular tissues, are reviewed. The primary outcomes of recent investigations in terms of morphological, structural, and in vitro and in vivo biological properties of the materials are discussed. The approaches based on the nature of the matrices employed to embed the HA reinforcements and produce the tissue substitutes are classified, and a critical discussion is provided on the presented state of the art as well as the future perspectives, to offer a comprehensive picture of the strategies investigated as well as challenges in this emerging field of materiomics.
Over the years, there has been an increasing number of cardiac and orthopaedic implanted medical devices, which has caused an increased incidence of device-associated infections. The surfaces of these indwelling devices are preferred sites for the development of biofilms that are potentially lethal for patients. Device-related infections form a large proportion of hospital-acquired infections and have a bearing on both morbidity and mortality. Treatment of these infections is limited to the use of systemic antibiotics with invasive revision surgeries, which had implications on healthcare burdens. The purpose of this review is to describe the main causes that lead to the onset of infection, highlighting both the biological and clinical pathophysiology. Both passive and active surface treatments have been used in the field of biomaterials to reduce the impact of these infections. This includes the use of antimicrobial peptides and ionic liquids in the preventive treatment of antibiotic-resistant biofilms. Thus far, multiple in vivo studies have shown efficacious effects against the antibiotic-resistant biofilm. However, this has yet to materialize in clinical medicine.
Fish industry by-products constitute an interesting platform for the extraction and recovery of valuable compounds in a circular economy approach. Among them, mussel shells could provide a calcium-rich source for the synthesis of hydroxyapatite (HA) bioceramics. In this work, HA nanoparticles have been successfully synthesized starting from mussel shells (Mytilus edulis) with a two steps process based on thermal treatment to convert CaCO3 in CaO and subsequent wet precipitation with a phosphorus source. Several parameters were studied, such as the temperature and gaseous atmosphere of the thermal treatment as well as the use of two different phosphorus-containing reagents in the wet precipitation. Data have revealed that the characteristics of the powders can be tailored, changing the conditions of the process. In particular, the use of (NH4)2HPO4 as the phosphorus source led to HA nanoparticles with a high crystallinity degree, while smaller nanoparticles with a higher surface area were obtained when H3PO4 was employed. Further, a selected HA sample was synthesized at the pilot scale; then, it was employed to fabricate porous 3D scaffolds using the direct foaming method. A highly porous scaffold with open and interconnected porosity associated with good mechanical properties (i.e., porosity in the range 87–89%, pore size in the range 50–300 μm, and a compressive strength σ = 0.51 ± 0.14 MPa) suitable for bone replacement was achieved. These results suggest that mussel shell by-products are effectively usable for the development of compounds of high added value in the biomedical field.
An optimized extraction protocol for eumelanins from black soldier flies (BSF-Eumel) allows an in-depth study of natural eumelanin pigments, which are a valuable tool for the design and fabrication of sustainable scaffolds. Here, water-soluble BSF-Eumel sub-micrometer colloidal particles were used as bioactive signals for developing a composite biomaterial ink for scaffold preparation. For this purpose, BSF-Eumel was characterized both chemically and morphologically; moreover, biological studies were carried out to investigate the dose-dependent cell viability and its influence on human mesenchymal stem cells (hMSCs), with the aim of validating suitable protocols and to find an optimal working concentration for eumelanin-based scaffold preparation. As proof of concept, 3D printed scaffolds based on methacrylated hyaluronic acid (MEHA) and BSF-Eumel were successfully produced. The scaffolds with and without BSF-Eumel were characterized in terms of their physico-chemical, mechanical and biological behaviours. The results showed that MEHA/BSF-Eumel scaffolds had similar storage modulus values to MEHA scaffolds. In terms of swelling ratio and stability, these scaffolds were able to retain their structure without significant changes over 21 days. Biological investigations demonstrated the ability of the bioactivated scaffolds to support the adhesion, proliferation and osteogenic differentiation of human mesenchymal stem cells.
Two different approaches are proposed in this study to enhance the bioactivity of hydroxyapatite-based scaffolds for bone tissue regeneration. The first method consists in a structural modification of Hydroxyapatite (HA) through doping it with Magnesium (1,3% wt) while the second one in using HA in combination with a calcium silicate, i.e. Wollastonite (WS), to form a composite bioceramic. Scaffolds with high and strongly interconnected porosity (pores ranging from 300 to 800 µm) were produced throughout both procedures. Higher mechanical properties in compression were obtained when the composite Ws/HA bioceramic was adopted. That one showed a weight loss after 6 months in physiological solution seven times higher than doped HA. Preliminary in vitro tests highlighted that both kinds of scaffold allowed the adhesion of MG63, without significant differences in terms of vitality, indicating a good biocompatibility of both used biomaterials.
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