The worldwide demand for the organ replacement or tissue regeneration is increasing steadily. The advancements in tissue engineering and regenerative medicine have made it possible to regenerate such damaged organs or tissues into functional organ or tissue with the help of 3D bioprinting. The main component of the 3D bioprinting is the bioink, which is crucial for the development of functional organs or tissue structures. The bioinks used in 3D printing technology require so many properties which are vital and need to be considered during the selection. Combination of different methods and enhancements in properties are required to develop more successful bioinks for the 3D printing of organs or tissue structures. This review consists of the recent state-of-art of polymer-based bioinks used in 3D printing for applications in tissue engineering and regenerative medicine. The subsection projects the basic requirements for the selection of successful bioinks for 3D printing and developing 3D tissues or organ structures using combinations of bioinks such as cells, biomedical polymers and biosignals. Different bioink materials and their properties related to the biocompatibility, printability, mechanical properties, which are recently reported for 3D printing are discussed in detail. Many bioinks formulations have been reported from cell-biomaterials based bioinks to cell-based bioinks such as cell aggregates and tissue spheroids for tissue engineering and regenerative medicine applications. Interestingly, more tunable bioinks, which are biocompatible for live cells, printable and mechanically stable after printing are emerging with the help of functional polymeric biomaterials, their modifications and blending of cells and hydrogels. These approaches show the immense potential of these bioinks to produce more complex tissue/organ structures using 3D bioprinting in the future.

/pdf/recent-trends-in-bioinks-for-3d-printing-3mb3rshzkc.pdf

Recent trends in bioinks for 3D printing.

During the resorbable-polymer-boom of the 1970s and 1980s, polycaprolactone (PCL) was used in the biomaterials field and a number of drug-delivery devices. Its popularity was soon superseded by faster resorbable polymers which had fewer perceived disadvantages associated with long term degradation (up to 3-4 years) and intracellular resorption pathways; consequently, PCL was almost forgotten for most of two decades. Recently, a resurgence of interest has propelled PCL back into the biomaterials-arena. The superior rheological and viscoelastic properties over many of its aliphatic polyester counterparts renders PCL easy to manufacture and manipulate into a large range of implants and devices. Coupled with relatively inexpensive production routes and FDA approval, this provides a promising platform for the production of longer-term degradable implants which may be manipulated physically, chemically and biologically to possess tailorable degradation kinetics to suit a specific anatomical site. This review will discuss the application of PCL as a biomaterial over the last two decades focusing on the advantages which have propagated its return into the spotlight with a particular focus on medical devices, drug delivery and tissue engineering.

The return of a forgotten polymer : Polycaprolactone in the 21st century

Three-dimensional (3D) printed scaffold and material selection for bone repair

Biofabrication aims to fabricate biologically functional products through bioprinting or bioassembly (Groll et al 2016 Biofabrication 8 013001). In biofabrication processes, cells are positioned at defined coordinates in three-dimensional space using automated and computer controlled techniques (Moroni et al 2018 Trends Biotechnol. 36 384-402), usually with the aid of biomaterials that are either (i) directly processed with the cells as suspensions/dispersions, (ii) deposited simultaneously in a separate printing process, or (iii) used as a transient support material. Materials that are suited for biofabrication are often referred to as bioinks and have become an important area of research within the field. In view of this special issue on bioinks, we aim herein to briefly summarize the historic evolution of this term within the field of biofabrication. Furthermore, we propose a simple but general definition of bioinks, and clarify its distinction from biomaterial inks.

https://iopscience.iop.org/article/10.1088/1758-5090/aaec52/pdf

A definition of bioinks and their distinction from biomaterial inks.

3D printing alias additive manufacturing can transform 3D virtual models created by computer-aided design (CAD) into physical 3D objects in a layer-by-layer manner dispensing with conventional molding or machining. Since the incipiency, significant advancements have been achieved in understanding the process of 3D printing and the relationship of component, structure, property and application of the created objects. Because hydrogels are one of the most feasible classes of ink materials for 3D printing and this field has been rapidly advancing, this Review focuses on hydrogel designs and development of advanced hydrogel-based biomaterial inks and bioinks for 3D printing. It covers 3D printing techniques including laser printing (stereolithography, two-photon polymerization), extrusion printing (3D plotting, direct ink writing), inkjet printing, 3D bioprinting, 4D printing and 4D bioprinting. It provides a comprehensive overview and discussion of the tailorability of material, mechanical, physical, chemical and biological properties of hydrogels to enable advanced hydrogel designs for 3D printing. The range of hydrogel-forming polymers covered encompasses biopolymers, synthetic polymers, polymer blends, nanocomposites, functional polymers, and cell-laden systems. The representative biomedical applications selected demonstrate how hydrogel-based 3D printing is being exploited in tissue engineering, regenerative medicine, cancer research, in vitro disease modeling, high-throughput drug screening, surgical preparation, soft robotics and flexible wearable electronics. Incomparable by thermoplastics, thermosets, ceramics and metals, hydrogel-based 3D printing is playing a pivotal role in the design and creation of advanced functional (bio)systems in a customizable way. An outlook on future directions of hydrogel-based 3D printing is presented.

3D printing of hydrogels: Rational design strategies and emerging biomedical applications

Composites consisting of calcium phosphate cements and mesoporous bioactive glasses as a 3D plottable drug delivery system.

Highly viscous bioinks offer great advantages for the three-dimensional fabrication of cell-laden constructs by microextrusion printing. However, no standardised method of mixing a high viscosity biomaterial ink and a cell suspension has been established so far, leading to non-reproducible printing results. A novel method for the homogeneous and reproducible mixing of the two components using a mixing unit connecting two syringes is developed and investigated. Several static mixing units, based on established mixing designs, were adapted and their functionality was determined by analysing specific features of the resulting bioink. As a model system, we selected a highly viscous ink consisting of fresh frozen human blood plasma, alginate, and methylcellulose, and a cell suspension containing immortalized human mesenchymal stem cells. This bioink is crosslinked after fabrication. A pre-crosslinked gellan gum-based bioink providing a different extrusion behaviour was introduced to validate the conclusions drawn from the model system. For characterisation, bioink from different zones within the mixing device was analysed by measurement of its viscosity, shape fidelity after printing and visual homogeneity. When taking all three parameters into account, a comprehensive and reliable comparison of the mixing quality was possible. In comparison to the established method of manual mixing inside a beaker using a spatula, a significantly higher proportion of viable cells was detected directly after mixing and plotting for both bioinks when the mixing unit was used. A screw-like mixing unit, termed “HighVisc”, was found to result in a homogenous bioink after a low number of mixing cycles while achieving high cell viability rates.

Homogeneous and Reproducible Mixing of Highly Viscous Biomaterial Inks and Cell Suspensions to Create Bioinks.

Patients with a simple transversal fracture of the olecranon are often treated with a tension band wiring (TBW), because it is known as a biomechanically appropriate and cost-effective procedure. Nevertheless, the technique is in detail more challenging than thought, resulting in a considerable high rate of implant-related complications like k-wire loosening and soft tissue irritation. In the literature, a distinction is generally only made between transcortical (bi-) and intramedullary (mono-) fixation of the wires. There is the additional possibility to fix the proximal bent end of k-wire in the cortex of the bone and thus create a tricortical fixation. The present study investigates the effectiveness of bi- and tricortical k-wire fixation in a biomechanical approach. TBW of the olecranon was performed at 10 cadaver ulnas from six donors in a usual manner and divided into two groups: In group 1, the k-wire was inserted by bicortical fixation (BC), and in group 2, a tricortical fixation (TC) was chosen. Failure behavior and maximum pullout strength were assessed and evaluated by using a Zwick machine. The statistical evaluation was descriptive and with a paired t test for the evaluation of significances between the two techniques. The average age of the used donors was 81.5 ± 11.5 (62–92) years. Three donors were female, and three were male. Ten k-wires were examined in BC group and 10 in the TC group. The mean bone density of the used proximal ulnas was on average 579 ± 186 (336–899) HU. The maximum pullout strength was 263 ± 106 (125–429) N in the BC group and increased significantly in the TC group to 325 ± 102 (144–466) N [p = .005]. This study confirms for the first time biomechanical superiority of tricortical k-wire fixation in the olecranon when using a TBW and may justify the clinical use of this method.

/pdf/biomechanical-comparison-of-bi-and-tricortical-k-wire-2e7y74b4u3.pdf

Biomechanical comparison of bi- and tricortical k-wire fixation in tension band wiring osteosynthesis.

Anatomically realistic organ replicas or phantoms allow for accurate studies and reproducible research. To recreate a human kidney, mimicry of the elastic properties of the human kidney is crucial. However, none of the related work addressed the design and development of a kidney phantom using only silicone as material. In contrast to paraffin and hydrogel, silicone is an ideal variant for its extended shelf life, soft-tissue-like feeling, and viscoelastic modularity. To this end, we conducted Uniaxial Compression testing and Cauchy stress modeling. Results indicate that none of the available manufacturer silicone brands are suitable for the task of creating a realistic kidney phantom. Indeed, the tested silicone mixtures in low and high strain fall outside the required approximate target compressive moduli of 20 kPa and 500 kPa, respectively. This work provides a frame of reference for future work by avoiding the pitfalls of the selected ready-made silicones and reusing the reported theoretical and experimental setup to design a realistic replica of the kidney organ.

/pdf/uniaxial-compression-testing-and-cauchy-stress-modeling-to-33big1zzs4.pdf

Tilman Ahlfeld

Papers

Composites consisting of calcium phosphate cements and mesoporous bioactive glasses as a 3D plottable drug delivery system.

Homogeneous and Reproducible Mixing of Highly Viscous Biomaterial Inks and Cell Suspensions to Create Bioinks.

Biomechanical comparison of bi- and tricortical k-wire fixation in tension band wiring osteosynthesis.

Uniaxial compression testing and Cauchy stress modeling to design anatomical silicone replicas.

3D-bioprinting of bone grafts for alveolar defects – a preclinical pilot study