Three-Dimensional Bioprinting for Cartilage Tissue Engineering: Insights into Naturally-Derived Bioinks from Land and Marine Sources

In regenerative medicine and tissue engineering, the possibility to: (I) customize the shape and size of scaffolds, (II) develop highly mimicked tissues with a precise digital control, (III) manufacture complex structures and (IV) reduce the wastes related to the production process, are the main advantages of additive manufacturing technologies such as three-dimensional (3D) bioprinting. Specifically, this technique, which uses suitable hydrogel-based bioinks, enriched with cells and/or growth factors, has received significant consideration, especially in cartilage tissue engineering (CTE). In this field of interest, it may allow mimicking the complex native zonal hyaline cartilage organization by further enhancing its biological cues. However, there are still some limitations that need to be overcome before 3D bioprinting may be globally used for scaffolds' development and their clinical translation. One of them is represented by the poor availability of appropriate, biocompatible and eco-friendly biomaterials, which should present a series of specific requirements to be used and transformed into a proper bioink for CTE. In this scenario, considering that, nowadays, the environmental decline is of the highest concerns worldwide, exploring naturally-derived hydrogels has attracted outstanding attention throughout the scientific community. For this reason, a comprehensive review of the naturally-derived hydrogels, commonly employed as bioinks in CTE, was carried out. In particular, the current state of art regarding eco-friendly and natural bioinks' development for CTE was explored. Overall, this paper gives an overview of 3D bioprinting for CTE to guide future research towards the development of more reliable, customized, eco-friendly and innovative strategies for this field of interest

Multipotential Role of Growth Factor Mimetic Peptides for Osteochondral Tissue Engineering

Articular cartilage is characterized by a poor self-healing capacity due to its aneural and avascular nature. Once injured, it undergoes a series of catabolic processes which lead to its progressive degeneration and the onset of a severe chronic disease called osteoarthritis (OA). In OA, important alterations of the morpho-functional organization occur in the cartilage extracellular matrix, involving all the nearby tissues, including the subchondral bone. Osteochondral engineering, based on a perfect combination of cells, biomaterials and biomolecules, is becoming increasingly successful for the regeneration of injured cartilage and underlying subchondral bone tissue. To this end, recently, several peptides have been explored as active molecules and enrichment motifs for the functionalization of biomaterials due to their ability to be easily chemically synthesized, as well as their tunable physico-chemical features, low immunogenicity issues and functional group modeling properties. In addition, they have shown a good aptitude to penetrate into the tissue due to their small size and stability at room temperature. In particular, growth-factor-derived peptides can play multiple functions in bone and cartilage repair, exhibiting chondrogenic/osteogenic differentiation properties. Among the most studied peptides, great attention has been paid to transforming growth factor-beta and bone morphogenetic protein mimetic peptides, cell-penetrating peptides, cell-binding peptides, self-assembling peptides and extracellular matrix-derived peptides. Moreover, recently, phage display technology is emerging as a powerful selection technique for obtaining functional peptides on a large scale and at a low cost. In particular, these peptides have demonstrated advantages such as high biocompatibility; the ability to be immobilized directly on chondro- and osteoinductive nanomaterials; and improving the cell attachment, differentiation, development and regeneration of osteochondral tissue. In this context, the aim of the present review was to go through the recent literature underlining the importance of studying novel functional motifs related to growth factor mimetic peptides that could be a useful tool in osteochondral repair strategies. Moreover, the review summarizes the current knowledge of the use of phage display peptides in osteochondral tissue regeneration

Reverse engineering of mandible and prosthetic framework: Effect of titanium implants in conjunction with titanium milled full arch bridge prostheses on the biomechanics of the mandible.

This study aimed at investigating the effects of titanium implants and different configurations of full-arch prostheses on the biomechanics of edentulous mandibles. Reverse engineered, composite, anisotropic, edentulous mandibles made of a poly(methylmethacrylate) core and a glass fibre reinforced outer shell were rapid prototyped and instrumented with strain gauges. Brånemark implants RP platforms in conjunction with titanium Procera one-piece or two-piece bridges were used to simulate oral rehabilitations. A lateral load through the gonion regions was used to test the biomechanical effects of the rehabilitations. In addition, strains due to misfit of the one-piece titanium bridge were compared to those produced by one-piece cast gold bridges. Milled titanium bridges had a better fit than cast gold bridges. The stress distribution in mandibular bone rehabilitated with a one-piece bridge was more perturbed than that observed with a two-piece bridge. In particular the former induced a stress concentration and stress shielding in the molar and symphysis regions, while for the latter design these stresses were strongly reduced. In conclusion, prosthetic frameworks changed the biomechanics of the mandible as a result of both their design and manufacturing technology

Bioactivation routes of gelatin-based scaffolds to enhance at nanoscale level bone tissue regeneration

The present work is focused on the development of gelatin-based scaffolds crosslinked through carbodiimide reaction and their bioactivation by two different methods: (i) surface modification by inorganic signals represented by hydroxyapatite nanoparticles precipitated on scaffold through biomimetic treatment; (ii) analog of BMP-2 peptide decoration. The results showed the effects of polymer concentration and crosslinking time on the physico-chemical, morphological, and mechanical properties of scaffolds. Furthermore, a comparative study of biological response for both bioactivated structures allowed to evaluate the influence of inorganic and organic cues on cellular behavior in terms of adhesion, proliferation and early osteogenic marker expression. The bioactivation by inorganic cues induced positive cellular response compared to neat scaffolds in terms of increased cell proliferation and early osteogenic differentiation of human mesenchymal stem cell (hMSC), as evidenced by the Alkaline phosphatase (ALP) expression. Similarly BMP-2 peptide decorated scaffolds showed higher values of ALP than biomineralized ones at longer time. The overall results demonstrated that the presence of bioactive signals (either inorganic or organic) at nanoscale level allowed an osteoinductive effect on hMSC in a basal medium, making the modified gelatin scaffolds a promising candidate for bone tissue regeneration

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

Hyaluronic acid as a bioink for extrusion-based 3D printing

Biofabrication is enriching the tissue engineering field with new ways of producing structurally organized complex tissues. Among the numerous bioinks under investigation, hyaluronic acid (HA) and its derivatives stand out for their biological relevance, cytocompatibility, shear-thinning properties, and potential to fine-tune the desired properties with chemical modification. In this paper, we review the recent advances on bioinks containing HA. The available literature is presented based on subjects including the rheological properties in connection with printability, the chemical strategies for endowing HA with the desired properties, the clinical application, the most advanced preclinical studies, the advantages and limitations in comparison with similar biopolymer-based bioinks, and future perspectives

Fabrication and characterisation of PCL and PCL/PLA scaffolds for tissue engineering

Purpose – The main purpose of this research work is to study the effect of poly lactic acid (PLA) addition into poly (e-caprolactone) (PCL) matrices, as well the influence of the mixing process on the morphological, thermal, chemical, mechanical and biological performance of the 3D constructs produced with a novel biomanufacturing device (BioCell Printing). Design/methodology/approach – Two mixing processes are used to prepare PCL/PLA blends, namely melt blending and solvent casting. PCL and PCL/PLA scaffolds are produced via BioCell Printing using a 300-μm nozzle, 0/90° lay down pattern and 350-μm pore size. Several techniques such as scanning electron microscopy (SEM), simultaneous thermal analyzer (STA), nuclear magnetic resonance (NMR), static compression analysis and Alamar BlueTM are used to evaluate scaffold's morphological, thermal, chemical, mechanical and biological properties. Findings – Results show that the addition of PLA to PCL scaffolds strongly improves the biomechanical performance of the constructs. Additionally, polymer blends obtained by solvent casting present better mechanical and biological properties, compared to blends prepared by melt blending. Originality/value – This paper undertakes a detailed study on the effect of the mixing process on the biomechanical properties of PCL/PLA scaffolds. Results will enable to prepare customized PCL/PLA scaffolds for tissue engineering applications with improved biological and mechanical properties, compared to PCL scaffolds alone. Additionally, the accuracy and reproducibility of by the BioCell Printing enables to modulate the micro/macro architecture of the scaffolds enhancing tissue regeneration. </jats:sec

Preliminary focus on the mechanical and antibacterial activity of a PMMA-based bone cement loaded with gold nanoparticles

In total knee arthroplasty (TKA) and total hip replacement (THR) the restoration of the normal joint function represents a fundamental feature. A prosthetic joint must be able to provide motions and to transmit functional loads. As reported in the literature, the stress distribution may be altered in bones after the implantation of a total joint prosthesis. Some scientific works have also correlated uncemented TKA to a progressive decrease of bone density below the tibial component. Antibiotic-loaded bone cements are commonly employed in conjunction with systemic antibiotics to treat infections. Furthermore, nanoparticles with antimicrobial activity have been widely analysed. Accordingly, the current research was focused on a preliminary analysis of the mechanical and antibacterial activity of a PMMA-based bone cement loaded with gold nanoparticles. The obtained results demonstrated that nanocomposite cements with a specific concentration of gold nanoparticles improved the punching performance and antibacterial activity. However, critical aspects were found in the optimization of the nanocomposite bone cement