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Whey protein isolate (WPI) hydrogels are attractive biomaterials for application in bone repair and regeneration. However, their main limitation is low mechanical strength. Therefore, to improve these properties, the incorporation of ceramic phases into hydrogel matrices is currently being performed. In this study, novel whey protein isolate/calcium silicate (WPI/CaSiO 3 ) hydrogel biomaterials were prepared with varying concentrations of a ceramic phase (CaSiO 3 ). The aim of this study was to investigate the effect of the introduction of CaSiO 3 to a WPI hydrogel matrix on its physicochemical, mechanical, and biological properties. Our Fourier Transform Infrared Spectroscopy results showed that CaSiO 3 was successfully incorporated into the WPI hydrogel matrix to create composite biomaterials. Swelling tests indicated that the addition of 5% ( w / v ) CaSiO 3 caused greater swelling compared to biomaterials without CaSiO 3 and ultimate compressive strength and strain at break. Cell culture experiments demonstrated that WPI hydrogel biomaterials enriched with CaSiO 3 demonstrated superior cytocompatibility in vitro compared to the control hydrogel biomaterials without CaSiO 3 . Thus, this study revealed that the addition of CaSiO 3 to WPI-based hydrogel biomaterials renders them more promising for bone tissue engineering applications.

In this work, composite filaments in the form of sticks and 3D-printed scaffolds were investigated as a future component of an osteochondral implant. The first part of the work focused on the development of a filament modified with bioglass (BG) and Zn-doped BG obtained by injection molding. The main outcome was the manufacture of bioactive, strong, and flexible filament sticks of the required length, diameter, and properties. Then, sticks were used for scaffold production. We investigated the effect of bioglass addition on the samples mechanical and biological properties. The samples were analyzed by scanning electron microscopy, optical microscopy, infrared spectroscopy, and microtomography. The effect of bioglass addition on changes in the SBF mineralization process and cell morphology was evaluated. The presence of a spatial microstructure within the scaffolds affects their mechanical properties by reducing them. The tensile strength of the scaffolds compared to filaments was lower by 58-61%. In vitro mineralization experiments showed that apatite formed on scaffolds modified with BG after 7 days of immersion in SBF. Scaffold with Zn-doped BG showed a retarded apatite formation. Innovative 3D-printing filaments containing bioglasses have been successfully applied to print bioactive scaffolds with the surface suitable for cell attachment and proliferation.

As the application of bone scaffolds becomes more and more widespread, the requirements for the high performance of bone scaffolds are also increasing. The stiffness and porosity of porous structures can be adjusted as needed, making them good candidates for repairing damaged bone tissues. However, the development of porous bone structures is limited by traditional manufacturing methods. Today, the development of additive manufacturing technology has made it very convenient to manufacture bionic porous bone structures as needed. In the present paper, the current state-of-the-art optimization techniques for designing the scaffolds and the settings of different optimization methods are introduced. Additionally, various design methods for bone scaffolds are reviewed. Furthermore, the challenges in designing high performance bone scaffolds and the future developments of bone scaffolds are also presented.

Bone scaffolds must fulfil numerous and sometimes contradictory characteristics: biocompatibility, bioactivity, high porosity, and appropriate mechanical strength. To tackle some of these issues, this study has several aims for the development of such scaffolds for dentistry applications: (i) to utilize appropriate materials (ceramics and sponges) and to introduce a novel, potentially performant ceramic material; (ii) to characterize the obtained scaffolds by using a range of methods; (iii) to compare and to correlate the assessment results with the scope to validate them reciprocally. There are two commercially available dental ceramics (i.e., Ceramco iC Natural Enamel (E) and Ceramco iC Natural Dentine (D), (DeguDent GmbH, Hanau-Wolfgang, Deutschland)) that are considered, as well as a new-developed porcelain (ceramic C). To obtain porous structures of scaffolds, each ceramic is introduced in two different sponges: a denser one, green (G) and a less dense one, blue (B). A total of 60 samples are manufactured and divided in six study groups, obtained by combining the above materials: GE, BE, GD, BD, GC, and BC (where the first letter represents the sponge type and the second one the utilized ceramic). Several methods are applied to characterize their chemical composition, as well as their macro- and micro-porosity: X-ray Diffraction (XRD), apparent porosity measurements, scanning electronic microscopy (SEM), and confocal microscopy (CM). The latter two methods image the inner (porous) and the outer/cortical (denser) areas of the samples. The results show a good porosity (i.e., dimensions and uniformity of pores) of around 65% for the final group BC, with satisfactory values of around 51% for BD and GC. A certain correlation is made between SEM, CM, and the apparent porosity results. The biocompatibility of the new ceramic C is demonstrated. Finally, a necessary trade-off is made with the mechanical strength of the obtained scaffolds, which was also evaluated. From this point of view, Group BD has the highest compressive strength of around 4 MPa, while Group BC comes second, with around 2 MPa. This trade-off between porosity and mechanical strength suggests a choice between Groups BC and BD, which are the best with regard to the porosity and mechanical strength criterium, respectively.

Additively manufactured Ti scaffolds have been used for bone replacement and orthopaedic applications. In these applications, both morphological and mechanical properties are important for their in vivo performance. Additively manufactured Ti6Al4V triply periodic minimal surface (TPMS) scaffolds with diamond and gyroid structures are known to have high stiffness and high osseointegration properties, respectively. However, morphological deviations between the as-designed and as-built types of these scaffolds have not been studied before. In this study, the morphological and mechanical properties of diamond and gyroid scaffolds at macro and microscales were examined. The results demonstrated that the mean printed strut thickness was greater than the designed target value. For diamond scaffolds, the deviation increased from 7.5 μm (2.5% excess) for vertical struts to 105.4 μm (35.1% excess) for horizontal struts. For the gyroid design, the corresponding deviations were larger, ranging from 12.6 μm (4.2% excess) to 198.6 μm (66.2% excess). The mean printed pore size was less than the designed target value. For diamonds, the deviation of the mean pore size from the designed value increased from 33.1 μm (-3.0% excess) for vertical struts to 92.8 μm (-8.4% excess) for horizontal struts. The corresponding deviation for gyroids was larger, ranging from 23.8 μm (-3.0% excess) to 168.7 μm (-21.1% excess). Compressive Young's modulus of the bulk sample, gyroid and diamond scaffolds was calculated to be 35.8 GPa, 6.81 GPa and 7.59 GPa, respectively, via the global compression method. The corresponding yield strength of the samples was measured to be 1012, 108 and 134 MPa. Average microhardness and Young's modulus from α and β phases of Ti6Al4V from scaffold struts were calculated to be 4.1 GPa and 131 GPa, respectively. The extracted morphology and mechanical properties in this study could help understand the deviation between the as-design and as-built matrices, which could help develop a design compensation strategy before the fabrication of the scaffolds.

A novel manufacturing approach was used to fabricate metallic scaffolds. A calibration of the laser cutting process was performed using the kerf width compensation in the calculations of the tool trajectory. Welding defects were studied through X-ray microtomography. Penetration depth and width resulted in relative errors of 9.4%, 1.0%, respectively. Microhardness was also measured, and the microstructure was studied in the base material. The microhardness values obtained were 400 HV, 237 HV, and 215 HV for the base material, HAZ, and fusion zone, respectively. No significant difference was found between the microhardness measurement along with different height positions of the scaffold. The scaffolds' dimensions and porosity were measured, their internal architecture was observed with micro-computed tomography. The results indicated that geometries with dimensions under 500 µm with different shapes resulted in relative errors of ~2.7%. The fabricated scaffolds presented an average compressive modulus ~13.15 GPa, which is close to cortical bone properties. The proposed methodology showed a promising future in bone tissue engineering applications.

Additive manufacturing is a valid solution to build complex geometries, including lightweight structures. Among these, gyroids offer a viable concept for bone tissue application, although many preliminary trials would be required to validate the design before actual implantation. In this frame, this study is aimed at presenting the background and the steps to build a numerical simulation to extract the mechanical behaviour of the structure, thus reducing the experimental effort. The results of the simulation are compared to the actual outcome resulting from quasi-static compressive tests and the effectiveness of the model is measured with reference to similar studies presented in the literature about other lightweight structures.

Ideal bone scaffolds for tissue engineering should be highly porous allowing cell attachment, spreading, and differentiation and presenting appropriate biomechanical properties. These antagonistic characteristics usually require extensive experimental work to achieve optimised balanced properties. This paper presents a simulation approach to determine the mechanical behaviour of bone scaffolds allowing the compressive modulus and the deformation mechanisms to be predicted. Polycaprolactone scaffolds with regular square pores and different porosities were considered. Scaffolds were also printed using an extrusion-based additive manufacturing and assessed under compressive loads. Similar designs were used for both simulation and fabrication steps. A good correlation between numerical and experimental results was obtained, highlighting the suitability of the simulation tool for the mechanical design of 3D-printed bone scaffolds.

In this review, we summarize the challenges of the three-dimensional (3D) printing of porous bioceramics and their translational hurdles to clinical applications. The state-of-the-art of the major 3D printing techniques (powder-based and slurry-based), their limitations and key processing parameters are discussed in detail. The significant roadblocks that prevent implementation of 3D printed bioceramics in tissue engineering strategies, and medical applications are outlined, and the future directions where new research may overcome the limitations are proposed. In recent years, there has been an increasing demand for a nanoscale control in 3D fabrication of bioceramic scaffolds via emerging techniques such as digital light processing, two-photon polymerization, or large area maskless photopolymerization. However, these techniques are still in a developmental stage and not capable of fabrication of large-sized bioceramic scaffolds; thus, there is a lack of sufficient data to evaluate their contribution. This review will also not cover polymer matrix composites reinforced with particulate bioceramics, hydrogels reinforced with particulate bioceramics, polymers coated with bioceramics and non-porous bioceramics.

Scaffolds for bone tissue engineering are porous structures that serve as support for cellular growth and, therefore, new tissue formation. The present work assessed the influence of the porous architecture of triply periodic minimal surface (TPMS) scaffolds on their macroscopic permeability behavior, combining numerical and experimental methods. The TPMS scaffolds considered were Schwartz D, Schwartz P, and Gyroid, which have been previously studied for bone tissue engineering, with 70% porosity. On the experimental side, these scaffolds were produced by MultiJet 3D printing and tested for fluid passage to calculate their permeability through Darcy's Law. On the numerical side, finite element (FE) models of the scaffolds were simulated on ABAQUS® for fluid passage under compression to assess potential fluid concentration spots. The outcomes revealed that the design of the unit cell had a noticeable effect on both calculated permeability and FE computed fluid flow velocity, regardless of the identical porosity, with the Gyroid scaffold having higher permeability and the Schwartz P a lower probability of fluid trapping. Schwartz D had the worst outcomes in both testing modalities, so these scaffolds would most likely be the last choice for promoting cell differentiation onto bone cells. Gyroid and Schwartz P would be up for selection depending on the application and targeted bone tissue., Competing Interests: The authors declare no conflict of interest.

Bone is a vascularized and connective tissue. The cortical bone is the main part responsible for the support and protection of the remaining systems and organs of the body. The trabecular spongy bone serves as the storage of ions and bone marrow. As a dynamic tissue, bone is in a constant remodelling process to adapt to the mechanical demands and to repair small lesions that may occur. Nevertheless, due to the increased incidence of bone disorders, the need for bone grafts has been growing over the past decades and the development of an ideal bone graft with optimal properties remains a clinical challenge. This review addresses the bone properties (morphology, composition, and their repair and regeneration capacity) and puts the focus on the potential strategies for developing bone repair and regeneration materials. It describes the requirements for designing a suitable scaffold material, types of materials (polymers, ceramics, and composites), and techniques to obtain the porous structures (additive manufacturing techniques like robocasting or derived from marine skeletons) for bone tissue engineering applications. Overall, the main objective of this review is to gather the knowledge on the materials and methods used for the production of scaffolds for bone tissue engineering and to highlight the potential of natural porous structures such as marine skeletons as promising alternative bone graft substitute materials without any further mineralogical changes, or after partial or total transformation into calcium phosphate.

Developments in selective laser melting (SLM) have enabled the fabrication of periodic cellular lattice structures characterized by suitable properties matching the bone tissue well and by fluid permeability from interconnected structures. These multifunctional performances are significantly affected by cell topology and constitutive properties of applied materials. In this respect, a diamond unit cell was designed in particular volume fractions corresponding to the host bone tissue and optimized with a smooth surface at nodes leading to fewer stress concentrations. There were 33 porous titanium samples with different volume fractions, from 1.28 to 18.6%, manufactured using SLM. All of them were performed under compressive load to determine the deformation and failure mechanisms, accompanied by an in-situ approach using digital image correlation (DIC) to reveal stress-strain evolution. The results showed that lattice structures manufactured by SLM exhibited comparable properties to those of trabecular bone, avoiding the effects of stress-shielding and increasing longevity of implants. The curvature of optimized surface can play a role in regulating the relationship between density and mechanical properties. Owing to the release of stress concentration from optimized surface, the failure mechanism of porous titanium has been changed from the pattern of bottom-up collapse by layer (or cell row) to that of the diagonal (45°) shear band, resulting in the significant enhancement of the structural strength., Competing Interests: The authors declare no conflict of interest.

The use of both bioglass (BG) and β tricalcium phosphate (β-TCP) for bone replacement applications has been studied extensively due to the materials' high biocompatibility and ability to resorb when implanted in the body. 3D printing has been explored as a fast and versatile technique for the fabrication of porous bone scaffolds. This project investigates the effects of using different combinations of a composite BG and β-TCP powder for 3D printing of porous bone scaffolds. Porous 3D powder printed bone scaffolds of BG, β-TCP, 50/50 BG/β-TCP and 70/30 BG/β-TCP compositions were subject to a variety of characterization and biocompatibility tests. The porosity characteristics, surface roughness, mechanical strength, viability for cell proliferation, material cytotoxicity and in vitro bioactivity were assessed. The results show that the scaffolds can support osteoblast-like MG-63 cells growth both on the surface of and within the scaffold material and do not show alarming cytotoxicity; the porosity and surface characteristics of the scaffolds are appropriate. Of the two tested composite materials, the 70/30 BG/β-TCP scaffold proved to be superior in terms of biocompatibility and mechanical strength. The mechanical strength of the scaffolds makes them unsuitable for load bearing applications. However, they can be useful for other applications such as bone fillers., Competing Interests: The authors declare no conflict of interest.