Hard Tissue Engineering Applications Research Articles

Influence of typographic biocomposite scaffold in facilitating biomineralization to progress complex hard tissue repair

Biomaterial modifications and scaffold fabrication methods in hard tissue engineering applications have seen enormous growth. However, clinical demand in treating and regenerating large bone defects is intricate, as current methods fail to meet requirements such as regenerating bone with optimal physical and mechanical properties in complex bone repair due to poor scaffold design and less bioactivity. To meet such clinical expectations, biomaterials are combined to create a 3D bone composite scaffold to improve the quality of the regenerated bone by improving bioactivity through biomineralization. To advance this process, accelerated and homogenous biomineralization is facilitated by the scaffold with increased surface area and active molecules to progress the repair of large bone defect. This facilitation of biomineralization leads to minerals deposition as a layer on the substrate when 3D-printed porous scaffolds made of biocomposite are exposed to body fluid at the repair site where the substrate degrades and releases active biomolecules. These released molecules crystallized evenly to form an apatite layer on the scaffold surface, where bone-forming cells attach, grow, and regenerate bone. Additionally, the formation of the apatite layer through biomineralization to repair lost structure is also governed by the following factors, which include macromolecules and an active site present between collagen molecules in the bone. In this review, we explore the advantages of biocomposite materials and 3D-printed scaffold design in accelerating biomineralization at the bone defect area to facilitate the formation of an apatite layer to progress complex hard tissue regeneration with optimal properties (1).

Preparation, Characterization, and Drug Delivery of Hexagonal Boron Nitride-Borate Bioactive Glass Biomimetic Scaffolds for Bone Tissue Engineering

In this study, biomimetic borate-based bioactive glass scaffolds containing hexagonal boron nitride hBN nanoparticles (0.1, 0.2, 0.5, 1, and 2% by weight) were manufactured with the polymer foam replication technique to be used in hard tissue engineering and drug delivery applications. To create three-dimensional cylindrical-shaped scaffolds, polyurethane foams were used as templates and covered using a suspension of glass and hBN powder mixture. Then, a heat treatment was applied at 570 °C in an air atmosphere to remove the polymer foam from the structure and to sinter the glass structures. The structural, morphological, and mechanical properties of the fabricated composites were examined in detail. The in vitro bioactivity of the prepared composites was tested in simulated body fluid, and the release behavior of gentamicin sulfate and 5-fluorouracil from glass scaffolds were analyzed separately as a function of time. The cytotoxicity was investigated using osteoblastic MC3T3-E1 cells. The findings indicated that the hBN nanoparticles, up to a certain concentration in the glass matrix, improved the mechanical strength of the glass scaffolds, which mimic the cancellous bone. Additionally, the inclusion of hBN nanoparticles enhanced the in vitro hydroxyapatite-forming ability of bioactive glass composites. The presence of hBN nanoparticles accelerated the drug release rates of the system. It was concluded that bioactive glass/hBN composite scaffolds mimicking native bone tissue could be used for bone tissue repair and regeneration applications.

Apatite-Graphene and Apatite-Graphene Oxide Nanocomposites: Hybrid Materials with Tailored Biological and Luminescent Properties

Apatite nanocomposites with graphene (G) or graphene oxide (GO) nanoflakes, as well as with related carbonaceous materials, present promising applications in hard tissue engineering, biomedicine, or drug delivery. Different methodologies have been explored in the last years to prepare apatite-based nanocomposites. Sitting drop vapour diffusion (SDVD) methodology induces the heterogeneous nucleation of biomimetic apatite on the reinforcement material, improving biological properties of the nanocomposites. In this work SDVD was used to prepare G-apatite and GO-apatite nanocomposites. Prior to the SDVD experiments, G flakes were obtained by sonication-assisted liquid-phase exfoliation (LPE) using L-Alanine (L-Aln) as dispersing biomolecule, while a commercial aqueous Graphene Oxide (GO) dispersion was used for the nucleation essays in presence of the same biomolecules. A parallel set of nucleation experiments was performed in presence of Tb3+ ions, to endow the nanocomposites of luminescent properties. Characterization by XRD, FTIR, and TEM demonstrated the heterogeneous nucleation of needle-shaped apatite nanocrystals on the surfaces of G and GO flakes. Fluorescence spectroscopy certified the presence of Tb3+ ions in the nanocomposites resulting in luminescent materials which can be used in imaging or theragnostic. Finally, in vitro tests with human mesenchymal stem cells revealed excellent cytocompatibility and cell proliferation in presence of the nanocomposites.

Effect of Boron-Doped Mesoporous Bioactive Glass Nanoparticles on C2C12 Cell Viability and Differentiation: Potential for Muscle Tissue Application.

Mesoporous bioactive glasses (MBGs) exhibit a high surface area and a highly ordered mesoporous structure. MBGs have potential for both hard and soft tissue engineering applications. MBGs may be doped with biologically active ions to tailor their biological activity. Boron is being widely studied as a dopant of bioactive glasses. Recently, research has demonstrated the potential of boron-containing bioactive glasses for muscle regeneration. In this study, boron-containing MBGs, 10B-MBG and 18B-MBG nanoparticles, were produced by a microemulsion-assisted sol-gel approach for potential muscle regeneration applications. First, X-ray diffraction (XRD), Fourier transform infrared (FTIR), and energy-dispersive X-ray spectroscopy (EDX) analyses were conducted to study the chemical structure and composition of the nanoparticles. To examine the nanoparticle morphology, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images were analyzed. Both SEM images and particle size distribution determined by dynamic light scattering (DLS) indicated a decrease of the average particle size after boron doping. TEM images indicated a slit-shaped mesoporous structure of nanoparticles for all compositions. The ζ potential was measured, and a negative surface charge was found for all study groups due to the presence of silanol groups. Cytocompatibility and fluorescence microscopy studies were also carried out. The results indicated that low concentrations (0.1 and 1 mg mL-1) of all MBG nanoparticles led to high viability of C2C12 cells. Fluorescence microscopy images indicated that at lower nanoparticle concentrations (0.1 and 1 mg mL-1), C2C12 cells appeared to differentiate into myotubes, which was indicated by a spindle-shaped morphology. For 10 mg mL-1 concentration of nanoparticles, C2C12 cells had a lower aspect ratio (estimated qualitatively by inspection of the images), which implied a lower degree of differentiation. Boron-doped MBG nanoparticles in reduced concentrations are suitable to induce differentiation of C2C12 cells into myotubes, indicating their potential for applications in muscle tissue repair.

Synthesis of Hydroxyapatite (HAp)-Zirconia Nanocomposite Powder and Evaluation of Its Biocompatibility: An In Vitro Study

A potential material for dental restorations and bone replacements is calcium phosphate (CaP)-based ceramic material. Nevertheless, its limited ability to withstand thermal processing and weak mechanical strength prevents it from being used in hard tissue engineering. Hydroxyapatite has been extensively used as a CaP-based biomaterial in prosthetic applications. On the other hand, zirconia is an inorganic material that combines outstanding mechanical capabilities with bioinert characteristics. In the present investigation, we demonstrated the reinforcement of zirconia in biomimetic hydroxyapatite (HAp) using a specially designed stir-type hydrothermal reactor to improve the biocompatibility and mechanical stability of bare hydroxyapatite. X-ray diffraction (XRD) analysis showed distinct peak shifts around 31° and 60°, which confirmed the formation of a nanocrystalline HAp-Zirconia composite without any intermediate phases. The size of the synthesized nanocomposite was found to be 30 nm using TEM. Further, the d-spacing value calculated from high-resolution transmission electron microscope (HRTEM) images corresponded to the distinct planes of the HAp (211) and zirconia (311) phases, respectively, in the composite powder. The in vitro cytotoxicity study revealed excellent biocompatibility with MG-63 human osteoblasts. Hence, the zirconia reinforced hydroxyapatite (HZ1) prepared in the present work could be utilized as a successful approach in a variety of hard tissue engineering applications.

Effect of porosity on mechanical and biological properties of bioprinted scaffolds.

Treatment of tissue defects commonly represents a major problem in clinics due to difficulties involving a shortage of donors, inappropriate sizes, abnormal shapes, and immunological rejection. While many scaffold parameters such as pore shape, porosity percentage, and pore connectivity could be adjusted to achieve desired mechanical and biological properties. These parameters are crucial scaffold parameters that can be accurately produced by 3D bioprinting technology based on the damaged tissue. In the present research, the effect of porosity percentage (40%, 50%, and 60%) and different pore shapes (square, star, and gyroid) on the mechanical (e.g., stiffness, compressive and tensile behavior) and biological (e.g., biodegradation, and cell viability) properties of porous polycaprolactone (PCL) scaffolds coated with gelatin have been investigated. Moreover, human foreskin fibroblast cells were cultured on the scaffolds in the in-vitro procedures. MTT assay (4, 7, and 14 days) was utilized to determine the cytotoxicity of the porous scaffolds. It is revealed that the porous scaffolds produced by the bioprinter did not produce a cytotoxic effect. Among all the porous scaffolds, scaffolds with a pore size of about 500 μm and porosity of 50% showed the best cell proliferation compared to the controls after 14 days. The results demonstrated that the pore shape, porosity percentage, and pore connectivity have an important role in improving the mechanical and biological properties of porous scaffolds. These 3D bioprinted biodegradable scaffolds exhibit potential for future application as polymeric scaffolds in hard tissue engineering applications.

An overview on electrospinning and its advancement toward hard and soft tissue engineering applications

One of the emerging technologies of the recent times harboring nanotechnology to fabricate nanofibers for various biomedical and environmental applications are electrospinning (nanofiber technology). Their relative ease in use, simplicity, functionality and diversity has surpassed the pitfalls encountered with the conventional method of generating fibers. This review aims to provide an overview of electrospinning, principle, methods, feed materials, and applications toward tissue engineering. To begin with, evolution of electrospinning and its typical apparatus have been briefed. Simultaneously, discussion on the production of nanofibers with diversified feed materials such as polymers, small molecules, colloids, and nanoparticles and its transformation into a powerful technology has been dealt with. Further, highlights on the application of nanofibers in tissue engineering and the commercialized products developed using nanofiber technology have been summed up. With this rapidly emerging technology, there would be a great demand pertaining to scalability and environmental challenge toward tissue engineering applications.

Comparative investigation on antibacterial, biological and mechanical behaviour of monticellite and diopside derived from biowaste for bone regeneration

Bioactive silicates have transpired as valuable biomaterials for hard tissue engineering applications owing to their bioactivity, biocompatibility and osteogenic activity. The compositions of ceramics are found to be the main reason for stimulating bone growth. To achieve the desired product for 100% clinical success, it is necessary to understand the relationship between composition and biological activity. The present probe explored the relationship between the composition and biological performance of silicate bioceramics (Monticellite and Diopside) prepared from biowaste. The phase purity of monticellite was achieved at 1200 °C and diopside at 900 °C. The evolution of gases during the combustion reaction resulted in porous samples. SEM micrographs revealed beehive-like morphology of monticellite whereas diopside possesses porous rock-like structures. The high phase formation temperature of monticellite was found to have a negligible influence on HAp deposition. Monticellite showed excellent apatite deposition and superior mechanical strength. The slow ionic release and their consumption during the dissolution of diopside indicate delayed biomineralization ability and controlled degradation. The occurrence of dissolution and degradation simultaneously in SBF was found to affect the apatite deposition ability as well as mechanical stability. Both monticellite and diopside restricted the growth of clinical pathogens causing the majority of bone infections. The Alamar Blue assay of monticellite and diopside demonstrated a good hBMSCs attachment and a significant proliferation. The Col1 and BMP2 osteogenic proteins expression suggested that both scaffolds can promote osteogenic differentiation of hBMSCs.

Polyhydroxyalkanoates and their advances for biomedical applications.

Polyhydroxyalkanoates (PHAs) are sustainable, versatile, biocompatible, and bioresorbable polymers that are suitable for biomedical applications. Produced via bacterial fermentation under nutrient-limiting conditions, they are uncovering a new horizon for devices in biomedical applications. A wide range of cell types including bone, cartilage, nerve, cardiac, and pancreatic cells, readily attach grow and are functional on PHAs. The tuneable physical properties and resorption rates of PHAs provide a toolbox for biomedical engineers in developing devices for hard and soft tissue engineering applications and drug delivery. The versatility of PHAs and the vast range of different PHA-based prototypes are discussed. Current in vitro, ex vivo, and in vivo development work are described and their regulatory approvals are reviewed.

Influence of Typographic Biocomposite Scaffold in Facilitating Biomineralization to Progress Complex Hard Tissue Repair

Biomaterial modifications and scaffold fabrication methods in hard tissue engineering applications have seen enormous growth. However, clinical demand in treating and regenerating large bone defects is intricate, as current methods fail to meet requirements such as regenerating bone with optimal physical and mechanical properties in complex bone repair due to poor scaffold design and less bioactivity. To meet such clinical expectations, biomaterials are combined to create a 3D bone composite scaffold to improve the quality of the regenerated bone by improving bioactivity through biomineralization. To advance this process, accelerated and homogenous biomineralization is facilitated by the scaffold with increased surface area and active molecules to progress the repair of large bone defect. This facilitation of biomineralization leads to minerals deposition as a layer on the substrate when 3D-printed porous scaffolds made of biocomposite are exposed to body fluid at the repair site where the substrate degrades and releases active biomolecules. These released molecules crystallized evenly to form an apatite layer on the scaffold surface, where bone-forming cells attach, grow, and regenerate bone. Additionally, the formation of the apatite layer through biomineralization to repair lost structure is also governed by the following factors, which include macromolecules and an active site present between collagen molecules in the bone. In this review, we explore the advantages of biocomposite materials and 3D-printed scaffold design in accelerating biomineralization at the bone defect area to facilitate the formation of an apatite layer to progress complex hard tissue regeneration with optimal properties [1].

Bioactive Coatings Loaded with Osteogenic Protein for Metallic Implants.

Osteoconductive and osteoinductive coatings represent attractive and tunable strategies towards the enhanced biomechanics and osseointegration of metallic implants, providing accurate local modulation of bone-to-implant interface. Composite materials based on polylactide (PLA) and hydroxyapatite (HAp) are proved beneficial substrates for the modulation of bone cells’ development, being suitable mechanical supports for the repair and regeneration of bone tissue. Moreover, the addition of osteogenic proteins represents the next step towards the fabrication of advanced biomaterials for hard tissue engineering applications, as their regulatory mechanisms beneficially contribute to the new bone formation. In this respect, laser-processed composites, based on PLA, Hap, and bone morphogenetic protein 4(BMP4), are herein proposed as bioactive coatings for metallic implants. The nanostructured coatings proved superior ability to promote the adhesion, viability, and proliferation of osteoprogenitor cells, without affecting their normal development and further sustaining the osteogenic differentiation of the cells. Our results are complementary to previous studies regarding the successful use of chemically BMP-modified biomaterials in orthopedic and orthodontic applications.

Fabrication of Hydroxyapatite with Bioglass Nanocomposite for Human Wharton's-Jelly-Derived Mesenchymal Stem Cell Growing Substrate.

Recently, composite scaffolding has found many applications in hard tissue engineering due to a number of desirable features. In this present study, hydroxyapatite/bioglass (HAp/BG) nanocomposite scaffolds were prepared in different ratios using a hydrothermal approach. The aim of this research was to evaluate the adhesion, growth, viability, and osteoblast differentiation behavior of human Wharton’s-jelly-derived mesenchymal stem cells (hWJMSCs) on HAp/BG in vitro as a scaffold for application in bone tissue engineering. Particle size and morphology were investigated by TEM and bioactivity was assessed and proven using SEM analysis with hWJMSCs in contact with the HAp/BG nanocomposite. Viability was evaluated using PrestoBlueTM assay and early osteoblast differentiation and mineralization behaviors were investigated by ALP activity and EDX analysis simultaneously. TEM results showed that the prepared HAp/BG nanocomposite had dimensions of less than 40 nm. The morphology of hWJMSCs showed a fibroblast-like shape, with a clear filopodia structure. The viability of hWJMSCs was highest for the HAp/BG nanocomposite with a 70:30 ratio of HAp to BG (HAp70/BG30). The in vitro biological results confirmed that HAp/BG composite was not cytotoxic. It was also observed that the biological performance of HAp70/BG30 was higher than HAp scaffold alone. In summary, HAp/BG scaffold combined with mesenchymal stem cells showed significant potential for bone repair applications in tissue engineering.

Polymer–ceramic biocomposites based on PVP/histidine/hydroxyapatite for hard tissue engineering applications

Polymer and hydroxyapatite (HAP) composites have growing interest in bone regeneration. Commonly used for these applications is polyvinylpyrrolidone (PVP), which represents excellent biological inertness, is biocompatible, and do not adversely interact with HAP. For this reason, in our studies, we have focused on 3-igreedient biocomposites based on PVP/histidine/HAP investigating their mechanical performance, morphology, swelling property and incubation response. The objective is to determine the effect of histidine on the UV cross-linked hydroxyapatite-polymers composites particularly focused on the role of their composition on structure, mechanical properties, and biocompatibility. The results confirm bioactivity of this material and it desirable features for orthopedics.

Recycled Porcine Bone Powder as Filler in Thermoplastic Composite Materials Enriched with Chitosan for a Bone Scaffold Application.

This work aims to synthesize biocompatible composite materials loaded with recycled porcine bone powder (BP) to fabricate scaffolds for in-situ reconstruction of bone structures. Polylactic acid (PLA) and poly(ε-caprolactone) (PCL) were tested as matrices in percentages from 40 wt% to 80 wt%. Chitosan (CS) was selected for its antibacterial properties, in the amount from 5 wt% to 15 wt%, and BP from 20 wt% to 50 wt% as active filler to promote osseointegration. In this preliminary investigation, samples have been produced by solvent casting to introduce the highest possible percentage of fillers. PCL has been chosen as a matrix due to its greater ability to incorporate fillers, ensuring their adequate dispersion and lower working temperatures compared to PLA. Tensile tests demonstrated strength properties (6–10 MPa) suitable for hard tissue engineering applications. Based on the different findings (integration of PLA in the composite system, improvements in CS adhesion and mechanical properties), the authors supposed an optimization of the synthesis process, focused on the possible implementation of the electrospinning technique to develop PCL-BP composites reinforced with PLA-CS microfibers. Finally, biological tests were conducted to evaluate the antibacterial activity of CS, demonstrating the applicability of the materials for the biomedical field.

A potential trackable bone filler: Preparation and characterization

AbstractThis study reported the synthesis of fluorescent hydroxyapatite/alginate/carbon quantum dots (HA/Alg/CQDs) nanocomposites via the co‐precipitation technique. The N‐doped CQDs as a new class of fluorescent materials were prepared by the citric acid pyrolysis method, with an average size around 4 nm. Physical, chemical, and optical properties of the synthesized nanocomposites were investigated by X‐ray diffraction (XRD), Fourier‐transformed infrared spectroscopy (FTIR), atomic force microscopy (AFM), field‐emission scanning electron microscopy (FESEM), UV–visible spectroscopy, and photoluminescence (PL) spectroscopy, respectively. The PL spectroscopy data verified the favorable in vitro luminescent emission of the HA/Alg/CQDs nanocomposites in comparison with HA/Alg and HA samples. The XRD patterns of the prepared samples confirmed the formation of crystalline HA in all composites, possessing a Ca/P ratio around 1.5 as obtained by EDX elemental analysis. The FESEM analysis exhibited HA nanoplates that homogeneously distributed throughout the alginate matrix. Therefore, the synthesized nanocomposites could be regarded as potential trackable drug carriers for hard tissue engineering applications.

Subcritical Water Extraction and Hydrolysis of Cod (Gadus morhua) Frames to Produce Bioactive Protein Extracts.

The valorization of Atlantic cod (Gadus morhua) frames from a filleting industry was investigated using subcritical water extraction and hydrolysis (SBW) at different temperatures (90, 140, 190 and 250 °C) and 100 bar to obtain extracts rich in proteins, peptides and amino acids. Up to 57.7 g of extract per 100 g of codfish frames were obtained, with nearly total recovery of the protein fraction. At each temperature, protein extracts of decreasing molecular weight were obtained, according to SEC-GPC results. Most of the protein present in the raw material and extracts was collagen and collagen fragments, as suggested by the amino acid profile. Codfish SBW extracts did not show cytotoxicity in the range of concentrations tested and the protein extract obtained at the lowest temperature (90 °C) showed the highest anti-inflammatory potential in human intestinal epithelium cell model. The mineralized residue left after SBW treatment of cod frames was identified as practically pure, crystalline, hydroxyapatite, that may find applications in biomedical field and hard-tissue engineering. This study shows the possible valorization of cod frames using green extraction methods such as SBW process to obtain protein extracts for food and nutraceutical applications.

Highly osteogenic and mechanically strong nanofibrous scaffolds based on functionalized multi-walled carbon nanotubes-reinforced electrospun keratin/poly(ε-caprolactone)

Here, we fabricated the electrospun scaffolds (so called PCL/Kr and PCL/Kr/CNT) based on poly(ε-caprolactone) (PCL), keratin (Kr), and carboxylated multiwalled carbon nanotubes (CNTs-COOH). Our goal was to evaluate the effect of CNTs-COOH on the osteogenic differentiation and mechanical and physicochemical properties of the scaffolds. We found that the addition of CNTs-COOH to the PCL/Kr scaffold reduced the average fiber diameter from 123 to 55 nm. As a result, the specific surface area of the scaffolds increased from 6 m2/g for the PCL/Kr scaffold to 15 m2/g for the PCL/Kr/CNT scaffold. Also, the PCL/Kr/CNT scaffold showed significantly higher tensile strength (8 vs 3 MPa) and modulus (114 vs 43 MPa) compared to the PCL/Kr scaffold. The formation of hydroxyapatite on the scaffolds incubated in simulated body fluid indicated the excellent osteoconductivity of the CNTs-containing scaffold. The presence of CNTs-COOH in the PCL/Kr/CNT scaffold also improved the osteogenic differentiation of mesenchymal stem cells as confirmed by the increased alkaline phosphatase activity and mineral formation on the surface of the scaffold. The PCL/Kr/CNT scaffold developed here can provide a mechanically strong construct with improved osteogenic properties for a variety of hard tissue engineering applications.

3D-printed biodegradable composite scaffolds with significantly enhanced mechanical properties via the combination of binder jetting and capillary rise infiltration process

For hard tissue engineering applications, biodegradable composite scaffolds have been extensively investigated because of their satisfactory mechanical properties and biocompatibility. Recently, 3D printing processes have received substantial attention in the tissue engineering field because of their ability to be customized for tissues that have suffered different types of loss or damage for each patient. However, previous studies on material extrusion-based techniques lack flexibility in the filler loading amount and cannot fulfill requirements that aim to enhance mechanical properties and biocompatibility. Herein, we propose a biodegradable polymer-based composite scaffolds with high ceramic loadings fabricated using the binder jetting (BJ) technique conjugated with capillary rise infiltration. A calcium sulfate hemihydrate (CSH) scaffold was fabricated using BJ-based 3D printing. Thereafter, CSH was transformed into biphasic calcium phosphate (BCP) using hydrothermal treatment, followed by heat treatment. Melted polycaprolactone (PCL) was infiltrated in the resulting BCP scaffold. BCP was then completely dispersed in the PCL matrix, and the calculated PCL loading in the BCP matrix exceeded 40 vol%. The PCL/BCP composite scaffold demonstrated the highest compressive strength, moduli, and toughness with the fracture mode shifted from brittle to less brittle. Moreover, a stable PCL/BCP surface promotes initial cell responses and shows sufficient proliferation and differentiation of pre-osteoblast cells.

3D Bioprinted Bacteriostatic Hyperelastic Bone Scaffold for Damage-Specific Bone Regeneration.

Current strategies for regeneration of large bone fractures yield limited clinical success mainly due to poor integration and healing. Multidisciplinary approaches in design and development of functional tissue engineered scaffolds are required to overcome these translational challenges. Here, a new generation of hyperelastic bone (HB) implants, loaded with superparamagnetic iron oxide nanoparticles (SPIONs), are 3D bioprinted and their regenerative effect on large non-healing bone fractures is studied. Scaffolds are bioprinted with the geometry that closely correspond to that of the bone defect, using an osteoconductive, highly elastic, surgically friendly bioink mainly composed of hydroxyapatite. Incorporation of SPIONs into HB bioink results in enhanced bacteriostatic properties of bone grafts while exhibiting no cytotoxicity. In vitro culture of mouse embryonic cells and human osteoblast-like cells remain viable and functional up to 14 days on printed HB scaffolds. Implantation of damage-specific bioprinted constructs into a rat model of femoral bone defect demonstrates significant regenerative effect over the 2-week time course. While no infection, immune rejection, or fibrotic encapsulation is observed, HB grafts show rapid integration with host tissue, ossification, and growth of new bone. These results suggest a great translational potential for 3D bioprinted HB scaffolds, laden with functional nanoparticles, for hard tissue engineering applications.

Natural Biomaterials and Their Use as Bioinks for Printing Tissues.

The most prevalent form of bioprinting—extrusion bioprinting—can generate structures from a diverse range of materials and viscosities. It can create personalized tissues that aid in drug testing and cancer research when used in combination with natural bioinks. This paper reviews natural bioinks and their properties and functions in hard and soft tissue engineering applications. It discusses agarose, alginate, cellulose, chitosan, collagen, decellularized extracellular matrix, dextran, fibrin, gelatin, gellan gum, hyaluronic acid, Matrigel, and silk. Multi-component bioinks are considered as a way to address the shortfalls of individual biomaterials. The mechanical, rheological, and cross-linking properties along with the cytocompatibility, cell viability, and printability of the bioinks are detailed as well. Future avenues for research into natural bioinks are then presented.