Table of Contents

Special Section: Bioprinting of 3D Functional Tissue Constructs

Regular Section

Review article

by Shweta Agarwala

Electrically conducting hydrogels are gaining increasing attention due to their potential application in smart patches, biosensors, functional tissue engineering scaffolds, wound management, and implants. The current review focuses on these novel materials, their synthesis routes, and their composites. Special attention is paid to fabrication routes to produce functional composites with organic and inorganic components. The design of conductive hydrogels leads to inheritance of the advantages of each component and offers new features from the synergistic effects between the components, thus opening new application areas. The review also discusses the emerging role of 3D printing as an advanced approach toward new design, functionality, and material combination possibilities. The issue of lack of the spatial control with current techniques is highlighted, and possible new routes to solve it are discussed. The review will provide readers with knowledge tool to select appropriate methodology for designing desired hydrogel material composites.

Original research article

by Ali Zolfagharian, Timothy M Gregory, Mahdi Bodaghi, Saleh Gharaie, Pearse Fay

Despite the frequency of mallet finger injuries, treatment options can often be costly, time-consuming, and ill-fitted. Three-dimensional (3D) printing allows for the production of highly customized and inexpensive splints, which suggests potential efficacy in the prescription of casts for musculoskeletal injuries. This study explores how the use of engineering concepts such as 3D printing and topology optimization (TO) can improve outcomes for patients. 3D printing enables the direct fabrication of the patient-specific complex shapes while utilizing finite element analysis and TO in the design of the splint allowed for the most efficient distribution of material to achieve mechanical requirements while reducing the amount of material used. The reduction in used material leads to significant improvements in weight reduction and heat dissipation, which would improve breathability and less sweating for the patient, greatly increasing comfort for the duration of their recovery.

Original research article

by Shengyang Chen, Tae-Sik Jang, Houwen Matthew Pan, Hyun-Do Jung, Ming Wei Sia, Shuying Xie, Yao Hang, Seow Khoon Mark Chong, Dongan Wang, Juha Song

Composite hydrogels have gained great attention as three-dimensional (3D) printing biomaterials because of their enhanced intrinsic mechanical strength and bioactivity compared to pure hydrogels. In most conventional printing methods for composite hydrogels, particles are preloaded in ink before printing, which often reduces the printability of composite ink with little mechanical improvement due to poor particle-hydrogel interaction of physical mixing. In contrast, the in situ incorporation of nanoparticles into a hydrogel during 3D printing achieves uniform distribution of particles with remarkable mechanical reinforcement, while precursors dissolved in inks do not influence the printing process. Herein, we introduced a “printing in liquid” technique coupled with a hybridization process, which allows 3D freeform printing of nanoparticle-reinforced composite hydrogels. A viscoplastic matrix for this printing system provides not only support for printed hydrogel filaments but also chemical reactants to induce various reactions in printed objects for in situ modification. Nanocomposite hydrogel scaffolds were successfully fabricated through this 3D freeform printing of hyaluronic acid (HAc)-alginate (Alg) hydrogel inks through a two-step crosslinking strategy. The first ionic crosslinking of Alg provided structural stability during printing, while the secondary crosslinking of photo-curable HAc improved the mechanical and physiological stability of the nanocomposite hydrogels. For in situ precipitation during 3D printing, phosphate ions were dissolved in the hydrogel ink and calcium ions were added to the viscoplastic matrix. The composite hydrogels demonstrated a significant improvement in mechanical strength, biostability, as well as biological performance compared to pure HAc. Moreover, the multi-material printing of composites with different calcium phosphate contents was achieved by adjusting the ionic concentration of inks. Our method greatly accelerates the 3D printing of various functional or hybridized materials with complex geometries through the design and modification of printing materials coupled with in situ post-printing functionalization and hybridization in reactive viscoplastic matrices.

Original research article

by Ali Zolfagharian, Martin Denk, Abbas Z. Kouzani, Mahdi Bodaghi, Saeid Nahavandi, Akif Kaynak

Recently, there has been a proliferation of soft robots and actuators that exhibit improved capabilities and adaptability through three-dimensional (3D) bioprinting. Flexibility and shape recovery attributes of stimuli-responsive polymers as the main components in the production of these dynamic structures enable soft manipulations in fragile environments, with potential applications in biomedical and food sectors. Topology optimization (TO), when used in conjunction with 3D bioprinting with optimal design features, offers new capabilities for efficient performance in compliant mechanisms. In this paper, multimaterial TO analysis is used to improve and control the bending performance of a bioprinted soft actuator with electrolytic stimulation. The multimaterial actuator performance is evaluated by the amplitude and rate of bending motion and compared with the single material printed actuator. The results demonstrated the efficacy of multimaterial 3D bioprinting optimization for the rate of actuation and bending.

Original research article

by Yanhao Hou, Weiguang Wang, Paulo Jorge Da Silva Bartolo

Scaffolds, three-dimensional (3D) substrates providing appropriate mechanical support and biological environments for new tissue formation, are the most common approaches in tissue engineering. To improve scaffold properties such as mechanical properties, surface characteristics, biocompatibility and biodegradability, different types of fillers have been used reinforcing biocompatible and biodegradable polymers. This paper investigates and compares the mechanical and biological behaviors of 3D printed poly(ε-caprolactone) scaffolds reinforced with graphene (G) and graphene oxide (GO) at different concentrations. Results show that contrary to G which improves mechanical properties and enhances cell attachment and proliferation, GO seems to show some cytotoxicity, particular at high contents.

Original research article

by Lung Chow, Kit-Lun Yick, Mei-Ying Kwan, Chun-Fai Yuen, Sun-Pui Ng, Annie Yu, Joanne Yip

Hypertrophic scars (HS) are considered to be the greatest unmet challenge in wound and burn rehabilitation. The most common treatment for HS is pressure therapy, but pressure garments may not be able to exert adequate pressure onto HS due to the complexity of the human body. However, the development of three-dimensional (3D) scanning and direct digital manufacturing technologies has facilitated the customized placement of additively manufactured silicone gel onto fabric as a component of the pressure therapy garment. This study provides an introduction on a novel and customized fabrication approach to treat HS and discusses the mechanical properties of 3D printed fabric reinforced with a silicone composite. For further demonstration of the suggested HS therapy with customized silicone insert, silicone inserts for the finger webs and HS were additively manufactured onto the fabric. Through the pressure evaluation by Pliance X system, it proved that silicone insert increases the pressure exerted to the HS. Moreover, the mechanical properties of the additively manufactured fabric silicone composites were characterized. The findings suggest that as compared with single viscosity print materials, the adhesive force of the additively manufactured silicone and fabric showed a remarkable improvement of 600% when print materials with different viscosities were applied onto elevated fabric.

Original research article

by Krishna C. R. Kolan, Yue-Wern Huang, Julie A. Semon, Ming C. Leu
The pore geometry of scaffold intended for the use in the bone repair or replacement is one of the most important parameters in bone tissue engineering. It affects not only the mechanical properties of the scaffold but also the amount of bone regeneration after implantation. Scaffolds with five different architectures (cubic, spherical, x, gyroid, and diamond) at different porosities were fabricated with bioactive borate glass using the selective laser sintering (SLS) process. The compressive strength of scaffolds with porosities ranging from 60% to 30% varied from 1.7 to 15.5 MPa. The scaffold’s compressive strength decreased significantly (up to 90%) after 1-week immersion in simulated body fluids. Degradation of scaffolds is dependent on porosity, in which the scaffold with the largest surface area has the largest reduction in strength. Scaffolds with traditional cubic architecture and biomimetic diamond architecture were implanted in 4.6 mm diameter full-thickness rat calvarial defects for 6 weeks to evaluate the bone regeneration with or without bone morphogenetic protein 2 (BMP-2). Histological analysis indicated no significant difference in bone formation in the defects treated with the two different architectures. However, the defects treated with the diamond architecture scaffolds had more fibrous tissue formation and thus have the potential for faster bone formation. Overall, the results indicated that borate glass scaffolds fabricated using the SLS process have the potential for bone repair and the addition of BMP-2 significantly improves bone regeneration.

Original research article

by Robert Owen, Colin Sherborne, Richard Evans, Gwendolen C. Reilly, Frederik Claeyssens

Bone has a hierarchy of porosity that is often overlooked when creating tissue engineering scaffolds where pore sizes are typically confined to a single order of magnitude. High internal phase emulsion (HIPE) templating produces polymerized HIPEs (polyHIPEs): highly interconnected porous polymers which have two length scales of porosity covering the 1–100 µm range. However, additional larger scales of porosity cannot be introduced in the standard emulsion formulation. Researchers have previously overcome this by additively manufacturing emulsions; fabricating highly microporous struts into complex macroporous geometries. This is time consuming and expensive; therefore, here we assessed the feasibility of combining porogen leaching with emulsion templating to introduce additional macroporosity. Alginate beads between 275 and 780 µm were incorporated into the emulsion at 0, 50, and 100 wt%. Once polymerized, alginate was dissolved leaving highly porous polyHIPE scaffolds with added macroporosity. The compressive modulus of the scaffolds decreased as alginate porogen content increased. Cellular performance was assessed using MLO-A5 post-osteoblasts. Seeding efficiency was significantly higher and mineralized matrix deposition was more uniformly deposited throughout porogen leached scaffolds compared to plain polyHIPEs. Deep cell infiltration only occurred in porogen leached scaffolds as detected by histology and lightsheet microscopy. This study reveals a quick, low cost and simple method of producing multiscale porosity scaffolds for tissue engineering.

Original research article

by Yijun Wong, Yihua Xu, Lifeng Kang, Kevin Yi-Lwern Yap
This study explored the potential of three-dimensional printing (3DP) technology in producing a three-dimensional (3D) medication label for blind and visually impaired (BVI) patients to ease their drug administration. Different variations of label wordings, dosing instructions, and medication identifiers were designed with reference to guidelines by the American Foundation for the Blind. Shapes and symbols were used as dosing instructions and medication identifiers to the patient’s medical conditions. Prototype designs were created with common graphics computer-assisted drafting software and 3D-printed using acrylonitrile butadiene styrene as the polymer filament. Feedback was then obtained from five people with normal vision and four BVI persons. The initial prototype comprised four components, namely, medication name and strength, patient’s name, dosing instruction, and medication identifier. A revised label comprising the latter two components was developed after feedback by BVI persons. Words were in all uppercase and regular font type, with a 5-mm center-to-center letter spacing. Elevation heights of the letters alternated between 1 mm and 1.5 mm. A half sphere represented the medication dose unit, while vertical lines and a horizontal center line with alternating elevation of arrowheads represented the frequency of administration and the medication’s consumption in relation to food, respectively. Symbols based on target organs were used as medication identifiers. With rapid advancements in 3DP technologies, there is tremendous potential for producing 3D labels in patients’ medication management.