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.

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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 Its popularity was soon superseded by faster resorbable polymers which had fewer perceived disadvantages associated with long term degradation (up to 3-4 years) and intracellular resorption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

Cement augmentation of pedicle screws is one of the most promising approaches to enhance the anchoring of screws in the osteoporotic spine. To date, there is no ideal cement for pedicle screw augmentation. The purpose of this study was to investigate whether an injectable, bioactive, and degradable calcium sulfate/hydroxyapatite (CaS/HA) cement could increase the maximum pull-out force of pedicle screws in osteoporotic vertebrae. Herein, 17 osteoporotic thoracic and lumbar vertebrae were obtained from a single fresh-frozen human cadaver and instrumented with fenestrated pedicle screws. The right screw in each vertebra was augmented with CaS/HA cement and the un-augmented left side served as a paired control. The cement distribution, interdigitation ability, and cement leakage were evaluated using radiographs. Furthermore, pull-out testing was used to evaluate the immediate mechanical effect of CaS/HA augmentation on the pedicle screws. The CaS/HA cement presented good distribution and interdigitation ability without leakage into the spinal canal. Augmentation significantly enhanced the maximum pull-out force of the pedicle screw in which the augmented side was 39.0% higher than the pedicle-screw-alone side. Therefore, the novel biodegradable biphasic CaS/HA cement could be a promising material for pedicle screw augmentation in the osteoporotic spine.

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Evaluation of an Injectable Biphasic Calcium Sulfate/Hydroxyapatite Cement for the Augmentation of Fenestrated Pedicle Screws in Osteoporotic Vertebrae: A Biomechanical Cadaver Study

Additive manufacturing of polymers and ceramics for tissue engineering applications

Design und Fertigung individueller, kunstlicher Ersatzgewebe sind grose Herausforderungen der biomedizinischen Forschung. Extrusionsbasierte additive Fertigungsmethoden eroffnen neue Moglichkeiten, um Biomaterialien nach einem individuellen Design anzuordnen. Der Schwerpunkt aktueller Forschungstatigkeiten liegt in der Generierung individueller biodegradierbarer Scaffolds sowie der Etablierung automatisierter Prozessketten zur Modellerstellung.

Bildgebungsbasiertes individuelles Design und additive Fertigung von osteochondralen Knochenersatzstrukturen

Their excellent mechanical properties, degradability and suitability for processing by 3D printing technologies make the thermoplastic polylactic acid and its derivatives favourable candidates for biomaterial-based bone regeneration therapies. In this study, we investigated whether bioactive mineral fillers, which are known to promote bone healing based on their dissolution products, can be integrated into a poly(L-lactic-co-glycolic) acid (PLLA-PGA) matrix and how key characteristics of degradation and cytocompatibility are influenced. The polymer powder was mixed with particles of CaCO3, SrCO3, strontium-modified hydroxyapatite (SrHAp) or tricalcium phosphates (α-TCP, β-TCP) in a mass ratio of 90 : 10; the resulting composite materials have been successfully processed into scaffolds by the additive manufacturing method Arburg Plastic Freeforming (APF). Degradation of the composite scaffolds was investigated in terms of dimensional change, bioactivity, ion (calcium, phosphate, strontium) release/uptake and pH development during long-term (70 days) incubation. The mineral fillers influenced the degradation behavior of the scaffolds to varying degrees, with the calcium phosphate phases showing a clear buffer effect and an acceptable dimensional increase. The amount of 10 wt% SrCO3 or SrHAp particles did not appear to be appropriate to release a sufficient amount of strontium ions to exert a biological effect in vitro. Cell culture experiments with the human osteosarcoma cell line SAOS-2 and human dental pulp stem cells (hDPSC) indicated the high cytocompatibility of the composites: For all material groups cell spreading and complete colonization of the scaffolds over the culture period of 14 days as well as an increase of the specific alkaline phosphatase activity, typical for osteogenic differentiation, were observed.

A comparative analysis of 3D printed scaffolds consisting of poly(lactic-co-glycolic) acid and different bioactive mineral fillers: aspects of degradation and cytocompatibility.

Tilman Ahlfeld

Papers

Evaluation of an Injectable Biphasic Calcium Sulfate/Hydroxyapatite Cement for the Augmentation of Fenestrated Pedicle Screws in Osteoporotic Vertebrae: A Biomechanical Cadaver Study

Additive manufacturing of polymers and ceramics for tissue engineering applications

Bildgebungsbasiertes individuelles Design und additive Fertigung von osteochondralen Knochenersatzstrukturen

A comparative analysis of 3D printed scaffolds consisting of poly(lactic-co-glycolic) acid and different bioactive mineral fillers: aspects of degradation and cytocompatibility.