In 2013, the “biofabrication window” was introduced to reflect the processing challenge for the fields of biofabrication and bioprinting. At that time, the lack of printable materials that could ...serve as cell‐laden bioinks, as well as the limitations of printing and assembly methods, presented a major constraint. However, recent developments have now resulted in the availability of a plethora of bioinks, new printing approaches, and the technological advancement of established techniques. Nevertheless, it remains largely unknown which materials and technical parameters are essential for the fabrication of intrinsically hierarchical cell–material constructs that truly mimic biologically functional tissue. In order to achieve this, it is urged that the field now shift its focus from materials and technologies toward the biological development of the resulting constructs. Therefore, herein, the recent material and technological advances since the introduction of the biofabrication window are briefly summarized, i.e., approaches how to generate shape, to then focus the discussion on how to acquire the biological function within this context. In particular, a vision of how biological function can evolve from the possibility to determine shape is outlined.
Advances in bioinks and bioprinting technologies have expanded the “biofabrication window”, achieving unprecedented resolution, shape fidelity, and mimicry of living tissues. The next challenge is guiding bioprinted constructs to mature, acquiring biological functions, to enable successful applications in regenerative medicine and advanced in vitro models. The vision of how biological function can evolve from the possibility to determine shape is outlined.
Bioprinting can be defined as the art of combining materials and cells to fabricate designed, hierarchical 3D hybrid constructs. Suitable materials, so called bioinks, have to comply with challenging ...rheological processing demands and rapidly form a stable hydrogel postprinting in a cytocompatible manner. Gelatin is often adopted for this purpose, usually modified with (meth‐)acryloyl functionalities for postfabrication curing by free radical photopolymerization, resulting in a hydrogel that is cross‐linked via nondegradable polymer chains of uncontrolled length. The application of allylated gelatin (GelAGE) as a thiol–ene clickable bioink for distinct biofabrication applications is reported. Curing of this system occurs via dimerization and yields a network with flexible properties that offer a wider biofabrication window than (meth‐)acryloyl chemistry, and without additional nondegradable components. An in‐depth analysis of GelAGE synthesis is conducted, and standard UV‐initiation is further compared with a recently described visible‐light‐initiator system for GelAGE hydrogel formation. It is demonstrated that GelAGE may serve as a platform bioink for several biofabrication technologies by fabricating constructs with high shape fidelity via lithography‐based (digital light processing) 3D printing and extrusion‐based 3D bioprinting, the latter supporting long‐term viability postprinting of encapsulated chondrocytes.
Allylated gelatin as a thiol–ene clickable bioink platform provides application for distinct biofabrication techniques. Cross‐linking of this cytocompatible system results in controlled homogeneous dimerized networks without additional nondegradable components, in contrast to conventional free radical polymerization. Moreover, UV‐ and visible‐light initiation of the hydrogels are compared.
We have demonstrated downsizing effects of the soft porous crystal, Zn(isophthalate)(4,4'-bipyridyl)(n) (CID-1), on the adsorption behavior between CID-1 and CID-1 nanocrystal (NCID-1). The ...difference results from the packing crystal structures and the dynamics of the frameworks.
Hydrogels are hydrophilic, highly water swellable polymer networks capable of converting chemical energy into mechanical energy and vice versa. They can be tailored regarding their chemical nature ...and physical structure, sensitiveness to external stimuli and biocompatibility; they can be formed in various structures and integrated into (micro-)systems. Accordingly, over the last decade, these materials have gained considerable recognition as valuable tool for sensors and in diagnostics. This article reviews the use of hydrogels in sensor development with focus on recent efforts in the application of stimuli responsive hydrogels as sensors, hydrogels as suitable matrices in which the sensing (bio-)molecules are embedded and hydrogels for modification and protection of sensor surfaces. In the first part of the review, both sensors and hydrogels are defined and a basic theoretical overview of hydrogels and their behavior is given. Subsequent chapters focus on hydrogels in physicochemical and biochemical sensing mechanisms with a primary emphasis on the hydrogels as such and the applied sensing mechanism. Finally, the review is concluded by a summary and discussion including an outlook on future perspectives for hydrogels in sensing applications.
The development and formulation of printable inks for extrusion-based 3D bioprinting has been a major challenge in the field of biofabrication. Inks, often polymer solutions with the addition of ...crosslinking to form hydrogels, must not only display adequate mechanical properties for the chosen application but also show high biocompatibility as well as printability. Here we describe a reproducible two-step method for the assessment of the printability of inks for bioprinting, focussing firstly on screening ink formulations to assess fibre formation and the ability to form 3D constructs before presenting a method for the rheological evaluation of inks to characterise the yield point, shear thinning and recovery behaviour. In conjunction, a mathematical model was formulated to provide a theoretical understanding of the pressure-driven, shear thinning extrusion of inks through needles in a bioprinter. The assessment methods were trialled with a commercially available crème, poloxamer 407, alginate-based inks and an alginate-gelatine composite material. Yield stress was investigated by applying a stress ramp to a number of inks, which demonstrated the necessity of high yield for printable materials. The shear thinning behaviour of the inks was then characterised by quantifying the degree of shear thinning and using the mathematical model to predict the window of printer operating parameters in which the materials could be printed. Furthermore, the model predicted high shear conditions and high residence times for cells at the walls of the needle and effects on cytocompatibility at different printing conditions. Finally, the ability of the materials to recover to their original viscosity after extrusion was examined using rotational recovery rheological measurements. Taken together, these assessment techniques revealed significant insights into the requirements for printable inks and shear conditions present during the extrusion process and allow the rapid and reproducible characterisation of a wide variety of inks for bioprinting.
Abstract Calcium phosphate cements (CPC) are well-established materials for the repair of bone defects with excellent biocompatibility and bioactivity. However, brittleness and low flexural/tensile ...strength so far restrict their application to non-load bearing areas. Reinforcement of CPC with fibers can substantially improve its strength and toughness and has been one major strategy to overcome the present mechanical limitations of CPC. Fiber reinforced calcium phosphate cements (FRCPC) thus bear the potential to facilitate the use of degradable bone substitutes in load bearing applications. This review recapitulates the state of the art of FRCPC research with focus on their mechanical properties and their biological evaluation in vitro and in vivo , including the clinical data that has been generated so far. After an overview on FRCPC constitutes and processing, some general aspects of fracture mechanics of reinforced cementitious composites are introduced, and their importance for the mechanical properties of FRCPC are highlighted. So far, fiber reinforcement leads to a toughness increase of up to two orders of magnitude. FRCPC have extensively been examined in vitro and in vivo with generally good results. While first clinical products focus on the improved performance of FRCPC with regard to secondary processing after injection such as fixation of screws and plates, first animal studies in load bearing applications show improved performance as compared to pure CPCs. Aside of the accomplished results, FRCPC bear a great potential for future development and optimization. Future research will have to focus on the selection and tailoring of FRCPC components, fiber–matrix compatibilization, integral composite design and the adjusted degradation behavior of the composite components to ensure successful long term behavior and make the composites strong enough for application in load bearing defects.
Fabricating a porous scaffold with high surface area has been a major strategy in the tissue engineering field. Among the many fabrication methods, electrospinning has become one of the cornerstone ...techniques due to its enabling the fabrication of highly porous fibrous scaffolds that are of natural or synthetic origin. Apart from the basic requirements of mechanical stability and biocompatibility, scaffolds are further expected to embody functional cues that drive cellular functions such as adhesion, spreading, proliferation, migration, and differentiation. There are abundant distinct approaches to introducing bioactive molecules to have a control over cellular functions. However, the lack of a thorough understanding of cell behavior with respect to the availability and spatial distribution of the bioactive molecules in 3D fibrous scaffolds is yet to be addressed. The rational selection of proper sets of characterization techniques would essentially impact the interpretation of the cell–scaffold interactions. In this timely Review, we summarize the most popular methods to introduce functional compounds to electrospun fibers. Thereafter, the strength and limitations of the conventional characterization methods are highlighted. Finally, the potential and applicability of emerging characterization techniques such as high-resolution/correlative microscopy approaches are further discussed.
Porous scaffolds are widely used in biomedical applications where pore size and morphology influence a range of biological processes, including mass transfer of solutes, cellular interactions and ...organization, immune responses, and tissue vascularization, as well as drug delivery from biomaterials. Ice templating, one of the most widely utilized techniques for the fabrication of porous materials, allows control over pore morphology by controlling ice formation in a suspension of solutes. By fine‐tuning freezing and solute parameters, ice templating can be used to incorporate pores with tunable morphological features into a wide range of materials using a simple, accessible, and scalable process. While soft matter is widely ice templated for biomedical applications and includes commercial and clinical products, the principles underpinning its ice templating are not reviewed as well as their inorganic counterparts. This review describes and critically evaluates fundamental principles, fabrication and characterization approaches, and biomedical applications of ice templating in polymer‐based biomaterials. It describes the utility of porous scaffolds in biomedical applications, highlighting biological mechanisms impacted by pore features, outlines the physical and thermodynamic mechanisms underpinning ice templating, describes common fabrication setups, critically evaluates complexities of ice templating specific to polymers, and discusses future directions in this field.
Ice templating is a simple, accessible, and scalable technique for the fabrication of porous materials. It allows control over the pore morphology by controlling ice formation in a material solution, suspension, or slurry. The fundamental principles, fabrication and characterization approaches, and biomedical applications of ice templating in polymer‐based biomaterials are reviewed.
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