Fabrication and characterization of 3D-printed composite scaffolds of coral-derived hydroxyapatite nanoparticles/polycaprolactone/gelatin carrying doxorubicin for bone tissue engineering.

In this study, nanocomposite scaffolds of hydroxyapatite (HA)/polycaprolactone (PCL)/gelatin (Gel) with varying amounts of HA (42-52 wt. %), PCL (42-52 wt. %), and Gel (6 wt. %) were 3D printed. Subsequently, a scaffold with optimal mechanical properties was utilized as a carrier for doxorubicin (DOX) in the treatment of bone cancer. For this purpose, HA nanoparticles were first synthesized by the hydrothermal conversion of Acropora coral and characterized by using different techniques. Also, a compression test was performed to investigate the mechanical properties of the fabricated scaffolds. The mineralization of the optimal scaffold was determined by immersing it in simulated body fluid (SBF) solution for 28 days, and the biocompatibility was investigated by seeding MG-63 osteoblast-like cells on it after 1-7 days. The obtained results showed that the average size of the synthesized HA particles was about 80 nm. The compressive modulus and strength of the scaffold with 47 wt. % HA was reported to be 0.29 GPa and 9.9 MPa, respectively, which was in the range of trabecular bones. In addition, the scaffold surface was entirely coated with an apatite layer after 28 days of soaking in SBF. Also, the efficiency and loading percentage of DOX were obtained as 30.8 and 1.6%, respectively. The drug release behavior was stable for 14 days. Cytotoxicity and adhesion evaluations showed that the fabricated scaffold had no negative effects on the viability of MG-63 cells and led to their proliferation during the investigated period. From these results, it can be concluded that the HA/PCL/Gel scaffold prepared in this study, in addition to its drug release capability, has good bioactivity, mechanical properties, and biocompatibility, and can be considered a suitable option for bone tumor treatment.

A route toward fabrication of 3D printed bone scaffolds based on poly(vinyl alcohol)-chitosan/bioactive glass by sol-gel chemistry.

Among different methods for the fabrication of bone scaffolds, 3D printing has created great advances in tissue engineering and regenerative medicine owing to its ability to make objects mimicking native tissues. Thanks to its abundant availability, structural features, and favorable biological properties, chitosan (CS) hydrogel was selected to be used for preparation of the bone scaffolds. However, the 3D printing of CS-based hydrogels is still under early exploration. Knowing the fact that natural polymers are not so competent at holding large amounts of water, poly(vinyl alcohol) as the second polymer was employed. The novelty of the present research lies in the concept of employing sol-gel chemistry in order to attain proper viscosity and rheological behavior to give self-standing filaments of the polymer blends. Employing sol-gel reaction in the preparation of the hybrid hydrogels had the advantage of endowing shape fidelity to the polymer blend without any solidifying in the needle. The obtained organic-inorganic hybrids were directly printed and subsequently cross-linked. The best performance in terms of mechanical strength, cell viability, and bio-mineralization was observed for the 50:50 ratio. The in vitro cell culture and the bioactivity results showed that the printed scaffolds with this method have great potential in bone tissue engineering. Further, this method could be expandable to print other hydrogels with diverse applications such as implantable devices, soft robotics, etc.

A Review on Antibacterial Biomaterials in Biomedical Applications: From Materials Perspective to Bioinks Design.

In tissue engineering, three-dimensional (3D) printing is an emerging approach to producing functioning tissue constructs to repair wounds and repair or replace sick tissue/organs. It allows for precise control of materials and other components in the tissue constructs in an automated way, potentially permitting great throughput production. An ink made using one or multiple biomaterials can be 3D printed into tissue constructs by the printing process; though promising in tissue engineering, the printed constructs have also been reported to have the ability to lead to the emergence of unforeseen illnesses and failure due to biomaterial-related infections. Numerous approaches and/or strategies have been developed to combat biomaterial-related infections, and among them, natural biomaterials, surface treatment of biomaterials, and incorporating inorganic agents have been widely employed for the construct fabrication by 3D printing. Despite various attempts to synthesize and/or optimize the inks for 3D printing, the incidence of infection in the implanted tissue constructs remains one of the most significant issues. For the first time, here we present an overview of inks with antibacterial properties for 3D printing, focusing on the principles and strategies to accomplish biomaterials with anti-infective properties, and the synthesis of metallic ion-containing ink, chitosan-containing inks, and other antibacterial inks. Related discussions regarding the mechanics of biofilm formation and antibacterial performance are also presented, along with future perspectives of the importance of developing printable inks.

Recent Trends in Three-Dimensional Bioinks Based on Alginate for Biomedical Applications.

Three-dimensional (3D) bioprinting is an appealing and revolutionary manufacturing approach for the accurate placement of biologics, such as living cells and extracellular matrix (ECM) components, in the form of a 3D hierarchical structure to fabricate synthetic multicellular tissues. Many synthetic and natural polymers are applied as cell printing bioinks. One of them, alginate (Alg), is an inexpensive biomaterial that is among the most examined hydrogel materials intended for vascular, cartilage, and bone tissue printing. It has also been studied pertaining to the liver, kidney, and skin, due to its excellent cell response and flexible gelation preparation through divalent ions including calcium. Nevertheless, Alg hydrogels possess certain negative aspects, including weak mechanical characteristics, poor printability, poor structural stability, and poor cell attachment, which may restrict its usage along with the 3D printing approach to prepare artificial tissue. In this review paper, we prepare the accessible materials to be able to encourage and boost new Alg-based bioink formulations with superior characteristics for upcoming purposes in drug delivery systems. Moreover, the major outcomes are discussed, and the outstanding concerns regarding this area and the scope for upcoming examination are outlined.

Three-Dimensional Printing Constructs Based on the Chitosan for Tissue Regeneration: State of the Art, Developing Directions and Prospect Trends.

Chitosan (CS) has gained particular attention in biomedical applications due to its biocompatibility, antibacterial feature, and biodegradability. Hence, many studies have focused on the manufacturing of CS films, scaffolds, particulate, and inks via different production methods. Nowadays, with the possibility of the precise adjustment of porosity size and shape, fiber size, suitable interconnectivity of pores, and creation of patient-specific constructs, 3D printing has overcome the limitations of many traditional manufacturing methods. Therefore, the fabrication of 3D printed CS scaffolds can lead to promising advances in tissue engineering and regenerative medicine. A review of additive manufacturing types, CS-based printed constructs, their usages as biomaterials, advantages, and drawbacks can open doors to optimize CS-based constructions for biomedical applications. The latest technological issues and upcoming capabilities of 3D printing with CS-based biopolymers for different applications are also discussed. This review article will act as a roadmap aiming to investigate chitosan as a new feedstock concerning various 3D printing approaches which may be employed in biomedical fields. In fact, the combination of 3D printing and CS-based biopolymers is extremely appealing particularly with regard to certain clinical purposes. Complications of 3D printing coupled with the challenges associated with materials should be recognized to help make this method feasible for wider clinical requirements. This strategy is currently gaining substantial attention in terms of several industrial biomedical products. In this review, the key 3D printing approaches along with revealing historical background are initially presented, and ultimately, the applications of different 3D printing techniques for fabricating chitosan constructs will be discussed. The recognition of essential complications and technical problems related to numerous 3D printing techniques and CS-based biopolymer choices according to clinical requirements is crucial. A comprehensive investigation will be required to encounter those challenges and to completely understand the possibilities of 3D printing in the foreseeable future.

The effects of crosslinkers on physical, mechanical, and cytotoxic properties of gelatin sponge prepared via in-situ gas foaming method as a tissue engineering scaffold.

In this study porous gelatin scaffolds were prepared using in-situ gas foaming, and four crosslinking agents were used to determine a biocompatible and effective crosslinker that is suitable for such a method. Crosslinkers used in this study included: hexamethylene diisocyanate (HMDI), poly(ethylene glycol) diglycidyl ether (epoxy), glutaraldehyde (GTA), and genipin. The prepared porous structures were analyzed using Fourier Transform Infrared Spectroscopy (FT-IR), thermal and mechanical analysis as well as water absorption analysis. The microstructures of the prepared samples were analyzed using Scanning Electron Microscopy (SEM). The effects of the crosslinking agents were studied on the cytotoxicity of the porous structure indirectly using MTT analysis. The affinity of L929 mouse fibroblast cells for attachment on the scaffold surfaces was investigated by direct cell seeding and DAPI-staining technique. It was shown that while all of the studied crosslinking agents were capable of stabilizing prepared gelatin scaffolds, there are noticeable differences among physical and mechanical properties of samples based on the crosslinker type. Epoxy-crosslinked scaffolds showed a higher capacity for water absorption and more uniform microstructures than the rest of crosslinked samples, whereas genipin and GTA-crosslinked scaffolds demonstrated higher mechanical strength. Cytotoxicity analysis showed the superior biocompatibility of the naturally occurring genipin in comparison with other synthetic crosslinking agents, in particular relative to GTA-crosslinked samples.

Gelatin porous scaffolds fabricated using a modified gas foaming technique: characterisation and cytotoxicity assessment.

The current study presents an effective and simple strategy to obtain stable porous scaffolds from gelatin via a gas foaming method. The technique exploits the intrinsic foaming ability of gelatin in the presence of CO2 to obtain a porous structure stabilised with glutaraldehyde. The produced scaffolds were characterised using physical and mechanical characterisation methods. The results showed that gas foaming may allow the tailoring of the 3-dimensional structure of the scaffolds with an interconnected porous structure. To assess the effectiveness of the preparation method in mitigating the potential cytotoxicity risk of using glutaraldehyde as a crosslinker, direct and in-direct cytotoxicity assays were performed at different concentrations of glutaraldehyde. The results indicate the potential of the gas foaming method, in the preparation of viable tissue engineering scaffolds.

Controllable synthesis and characterization of porous polyvinyl alcohol/hydroxyapatite nanocomposite scaffolds via an in situ colloidal technique.

During the last decades, there have been several attempts to combine bioactive materials with biocompatible and biodegradable polymers to create nanocomposite scaffolds with excellent biocompatibility, bioactivity, biodegradability and mechanical properties. In this research, the nanocomposite scaffolds with compositions based on PVA and HAp nanoparticles were successfully prepared using colloidal HAp nanoparticles combined with freeze-drying technique for tissue engineering applications. In addition, the effect of the pH value of the reactive solution and different percentages of PVA and HAp on the synthesis of PVA/HAp nanocomposites were investigated. The SEM observations revealed that the prepared scaffolds were porous with three dimensional microstructures, and in vitro experiments with osteoblast cells indicated an appropriate penetration of the cells into the scaffold's pores, and also the continuous increase in cell aggregation on the scaffolds with increase in the incubation time demonstrated the ability of the scaffolds to support cell growth. According to the obtained results, the nanocomposite scaffolds could be considered as highly bioactive and potential bone tissue engineering implants.