rett syndrome (rtt) is a rare, neurodevelopmental disorder primarily affecting females1 often resulting in early loss of acquired skills including hand use, walking, and verbal communication. disorders of gastrointestinal (gi) motility such as gastroesophageal reflux disease (gerd) and constipation are common for individuals diagnosed with rtt. few studies have examined the characteristics, clinical sequalae, medication and healthcare service utilization in response to gi comorbidities associated with rtt.

Background: One of the main challenges for extrusion 3D bioprinting is the identification of non-synthetic bioinks with suitable rheological properties and biocompatibility. Our aim was to optimize and compare the printability of crystal, fibril and blend formulations of novel pulp derived nanocellulose bioinks and assess biocompatibility with human nasoseptal chondrocytes. Methods: The printability of crystalline, fibrillated and blend formulations of nanocellulose was determined by assessing resolution (grid-line assay), post-printing shape fidelity and rheology (elasticity, viscosity and shear thinning characteristics) and compared these to pure alginate bioinks. The optimized nanocellulose-alginate bioink was bioprinted with human nasoseptal chondrocytes to determine cytotoxicity, metabolic activity and bioprinted construct topography. Results: All nanocellulose-alginate bioink combinations demonstrated a high degree of shear thinning with reversible stress softening behavior which contributed to post-printing shape fidelity. The unique blend of crystal and fibril nanocellulose bioink exhibited nano- as well as micro-roughness for cellular survival and differentiation, as well as maintaining the most stable construct volume in culture. Human nasoseptal chondrocytes demonstrated high metabolic activity post printing and adopted a rounded chondrogenic phenotype after prolonged culture. Conclusions: This study highlights the favorable rheological, swelling and biocompatibility properties of nanocellulose-alginate bioinks for extrusion-based bioprinting.

Affimer proteins can bind to a wide variety of target molecules. They can complement and represent a promising alternative to conventional antibodies as they can target molecules with high affinity, specificity, and stability. In addition, they can be selected and expressed in bacterial and mammalian systems. Affimer protein technology shows promise as a tool in the biologist's arsenal of the future in imaging, diagnostic, and therapeutic applications.

Congenital or acquired tissue loss and dysfunction is an enormous socioeconomic burden for healthcare systems globally. Tissue engineering holds promise to repair or replace human tissues and organs in order to restore normal function. One facet of tissue engineering is three-dimensional (3D) bioprinting which has emerged as an attractive method for assembling living and nonliving biological materials into spatially controlled, precise, and well-defined structures. It is essential that bioinks have the desired functional and mechanical properties that closely match the tissue it is to replace. Therefore it is imperative to correlate process and print parameters and factors that affect printability with shape fidelity and print resolution of the final fabricated 3D construct.

Bacterial species are now being mixed with various bioinks to produce functional complex materials using 3D printing. These systems show enormous potential in applications such as bioremediation, sensors that can detect toxic chemicals, oil spill filters, and wound dressings. In particular, 3D-printed minibiofactories represent a potential paradigm shift in biotechnology.

Bioinspiration from hierarchical structures found in natural environments has heralded a new age of advanced functional materials. Nanocellulose has received significant attention due to the demand for high-performance materials with tailored mechanical, physical and biological properties. In this study, nanocellulose fibrils, nanocrystals and a novel mixture of fibrils and nanocrystals (blend) were prepared from softwood biomass using the AVAP® biorefinery technology. These materials were characterized using transmission and scanning electron microscopy, and atomic force microscopy. This analysis revealed a nano- and microarchitecture with extensive porosity. Notable differences included the nanocrystals exhibiting a compact packing of nanorods with reduced porosity. The NC blend exhibited porous fibrillar networks with interconnecting compact nanorods. Fourier transform infrared spectroscopy and X-ray diffraction confirmed a pure cellulose I structure. Thermal studies highlighted the excellent stability of all three NC materials with the nanocrystals having the highest decomposition temperature. Surface charge analysis revealed stable colloid suspensions. Rheological studies highlighted a dominance of elasticity in all variants, with the NC blend being more rigid than the NC fibrils and nanocrystals, indicating a double network hydrogel structure. Given these properties, it is thought that these materials show great potential in (bio)nanomaterial applications where careful control of microarchitecture, surface topography and porosity are required.

Journal of 3D Printing in MedicineVol. 2, No. 1 EditorialFree AccessTo print or not to print, that is the question: how close are we to clinical translation of contemporary bioinks?Stuart Kyle & Iain S WhitakerStuart Kyle*Author for correspondence: E-mail Address: stuart.kyle@doctors.org.uk Reconstructive Surgery & Regenerative Medicine Research Group (www.ReconRegen.com), Institute of Life Sciences, Swansea University Medical School, Swansea, SA2 8PP, UK The Welsh Centre for Burns & Plastic Surgery, Morriston Hospital, Swansea, SA6 6NL, UK & Iain S Whitaker**Author for correspondence: E-mail Address: iainwhitaker@fastmail.fm Reconstructive Surgery & Regenerative Medicine Research Group (www.ReconRegen.com), Institute of Life Sciences, Swansea University Medical School, Swansea, SA2 8PP, UK The Welsh Centre for Burns & Plastic Surgery, Morriston Hospital, Swansea, SA6 6NL, UKPublished Online:15 Dec 2017https://doi.org/10.2217/3dp-2017-0021AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: 3D printingbiofabricationbioprintingprintabilityprint resolutionshape fidelitystructural integrityDespite the continual addition of names to organ transplant registers worldwide, and the many millions of individuals with tissue loss resulting in structural, cosmetic and functional problems, there is still no sustainable solution. One promising approach to alleviate these problems and revolutionize current medical treatments is biofabrication, which over the last decade has rapidly evolved from a niche research area into more mainstream, integrated bioprinting platforms. The success of this shift has been attributed to advances in engineering of bioprinters using automated robotics that have enabled bioinks to be temporo–spatially deposited layer-by-layer in 3D in a precise manner. Certain systems have become more economically viable for custom-made production and, in combination with advances in 3D medical imaging, offer the potential to replace tissues and organs in a scalable, patient-specific approach revolutionizing personalized medicine.Biofabrication falls within the multidisciplinary field of tissue engineering that aims to create or restore tissues and/or organs through hierarchical assembly of cells, bioactive/biofunctional molecules and biomaterials/bioinks into well-defined composite structures. This approach relies on careful interplay between the 'printability' of biomaterials, the ability to incorporate cells and enhance viability and durability. Next-generation bioinks are now being designed to improve shape and print fidelity through careful control of printing parameters while maintaining physicochemical and biological properties. We have recently reviewed the current state of play in understanding the importance of 'printability' of bioinks in order to dispense small units of cells and biomaterials with micrometer precision and high resolution so that tissue-like structures can be fabricated [1].In the biofabrication and bioprinting community, we consider 'printability' as the relationship between bioinks and substrates that results in the layer-by-layer additive manufacturing of accurate, well-defined structures with structural fidelity and integrity. The added complexity that comes with the introduction of living cells is the next challenge, as is the delivery in a well-controlled micro- and macro-environment.The key areas to consider while assessing 'printability' are the manipulation and control of nozzle and printing parameters, and the interaction between the bioink and substrate when forming the first layer. This means that both the printing on the substrate surface and the subsequent 'layer-on-layer' must have tunable properties, and ensure that each layer can withstand forces imposed upon them to maintain structural integrity. A deep insight into the physics of bioprinting is important, to allow understanding of varying contact angles and surface tensions between bioinks and substrates. Coating with thin polymer layers is often used to enhance the printing surface.Viscosity and rheology of bioinks are key parameters for successful extrusion-based 3D bioprinting that are gaining further attention in research communities worldwide. As viscosity is determined by bioink concentration, molecular weight and temperature, low viscosity bioinks lead to structural collapse of printed structures. Sufficient viscosity is required to overcome surface tension forces and the formation of continuous extruded filaments. The optimal situation is the formation of separate elegant filaments resulting in cylindrical rather than spheroidal shapes. The refinement and accurate control of shear thinning behavior of bioinks will also be essential in improving print resolution and shape fidelity of complex, 3D structures. The balance of shear stress and viscosity is the key issue as they are not working synergistically: decreased viscosity and hence shear stress favors cell survival whereas higher viscosities result in print fidelity. The aim is to encapsulate cells with >95% viability within bioinks of sufficiently high viscosity deposited via a precise nozzle. Carefully selected bioinks at optimal concentrations and molecular weights lead to better printability while providing enhanced microenvironments for cell differentiation, migration, proliferation and extracellular matrix formation.A number of strategies have been adopted to address this trade-off between 'printability' and cell biology within complex 3D geometries. Rheological modifiers or 'thickening agents' enhance the viscoelastic properties, which help to improve: filament/line printing; mechanical properties; cell encapsulation and viability; and, pore geometry and structural integrity. Various crosslinking systems have also been employed to allow the extrusion of cell-laden polymer solutions in combination with immediate gelation to improve print fidelity. Contemporary crosslinking techniques involve the use of chemicals, heat, UV light or a mixture of strategies. 'Support baths' and a range of delivery methods, such as spraying, have been used to create an environment conducive to crosslinking. The incorporation of sacrificial materials, such as agarose, gelatin and alginate, is currently being trialed to enhance mechanical support and strength.Advances in computer simulation, imaging and modelling are incrementally advancing the biofabrication of smart, tunable, responsive and multifunctional materials within the 3D bioprinting arena. The revolution in 3D bioprinting by imaging, designing and printing complex geometries is fuelled by increased computational power. Advanced biological imaging is also allowing study of the interaction between the material/cell interface at the 'nano' level.Due to recent advances in technology, knowledge and equipment, we are currently in a position to image, design and bioprint tissues of clinically relevant and patient-specific sizes. We have the ability to temporo–spatially place multiple cell types in 3D in order to biomimic the native tissue histoarchitecture. The current major hurdle to clinical translation of 3D printed tissue is durability for their targeted applications. There are many biological and technological strategies being employed to this end, alongside computer simulations to predict changes in structure and function of bioprinted materials.Although research in the area of 3D bioprinting is evolving at a rapid pace, there are very few examples of successful clinical translation. The future is exciting, with the prospect of multimaterial bioinks that are smart, adaptive and multifunctional. Through incremental improvements and rationalized design, we expect such materials to maintain excellent 'printability' and shape fidelity alongside enhanced mechanical and biomimetic properties. A better understanding of the surface interactions and functionalization will enhance the physicochemical and biological properties of next-generation bioinks. Other factors impacting clinical translation that must also be considered include degradability, support of vascularization and migration of endogenous progenitor cells, implantability, affordability, commercial availability and anti-immunogenicity of bioinks. Continual advances in medical knowledge, engineering and technology means 3D bioprinting has the potential to revolutionize personalized medicine within a generation. The fabrication of complex, heterogeneous and multicellular constructs, at scales with clinical relevance, is an exciting prospect for the future. It is definitely a question of 'when' will we see the routine use of 3D bioprinted tissues and organs clinically, not 'if'.Financial & competing interest disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.References1 Kyle S, Jessop Z, Al-Sabah A, Whitaker I. 'Printability' of candidate biomaterials for extrusion based 3D printing: state of the art. Adv. Healthcare Mater. 6(16), doi: 10.1002/adhm.201700264 (2017).Medline, Google ScholarFiguresReferencesRelatedDetailsCited By3D Printing and Nanotechnology: A Multiscale Alliance in Personalized Medicine11 February 2021 | Advanced Functional Materials, Vol. 31, No. 163D Bioprinting for Organs, Skin, and Engineered Tissues Vol. 2, No. 1 Follow us on social media for the latest updates Metrics History Received 28 September 2017 Accepted 17 November 2017 Published online 15 December 2017 Published in print January 2018 Information© 2017 Future Medicine LtdKeywords3D printingbiofabricationbioprintingprintabilityprint resolutionshape fidelitystructural integrityFinancial & competing interest disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Regenerative medicine has been highlighted as one of the UK's 8 'Great Technologies' with the potential to revolutionize patient care in the 21st Century. Over the last decade, the concept of '3D bioprinting' has emerged, which allows the precise deposition of cell laden bioinks with the aim of engineering complex, functional tissues. For 3D printing to be used clinically, there is the need to produce advanced functional biomaterials, a new generation of bioinks with suitable cell culture and high shape/print fidelity, to match or exceed the physical, chemical and biological properties of human tissue. With the rapid increase in knowledge associated with biomaterials, cell-scaffold interactions and the ability to biofunctionalize/decorate bioinks with cell recognition sequences, it is important to keep in mind the 'printability' of these novel materials. In this illustrated review, we define and refine the concept of 'printability' and review seminal and contemporary studies to highlight the current 'state of play' in the field with a focus on bioink composition and concentration, manipulation of nozzle parameters and rheological properties.

3D bioprinting has the potential to replicate complex tissue architecture and biomanufacture physiologically relevant multicellular constructs on demand. In article number 1700264, Stuart Kyle, Iain S. Whitaker, and co-workers review a new generation of bioinks with suitable biocompatibility and high shape/print fidelity, that have the potential to match or exceed the physical, chemical and biological properties of human tissue, when combined with the appropriate cell source. Image of 3D Bioprinter kindly provided by Aether.

Over the years, nanotechnology has greatly developed, moving from careful design strategies and synthesis of novel nanostructures to producing them for specific medical and biological applications. The use of nanotechnology in diagnostics, drug delivery, and tissue engineering holds great promise for the treatment of stroke in the future. Nanoparticles are employed to monitor grafted cells upon implantation, or to enhance the imagery of the tissue, which is coupled with a noninvasive imaging modality such as magnetic resonance imaging, computed axial tomography or positron emission tomography scan. Contrast imaging agents used can range from iron oxide, perfluorocarbon, cerium oxide or platinum nanoparticles to quantum dots. The use of nanomaterial scaffolds for neuroregeneration is another area of nanomedicine, which involves the creation of an extracellular matrix mimic that not only serves as a structural support but promotes neuronal growth, inhibits glial differentiation, and controls hemostasis. Promisingly, carbon nanotubes can act as scaffolds for stem cell therapy and functionalizing these scaffolds may enhance their therapeutic potential for treatment of stroke. This Progress Report highlights the recent developments in nanotechnology for the detection and therapy of stroke. Recent advances in the use of nanomaterials as tissue engineering scaffolds for neuroregeneration will also be discussed.

Patients who understand their injuries, the aims and potential of their treatment are likely to experience superior outcomes. We review the literature on positive, encouraging doctor–patient communication, and the impact of health literacy and education on patient knowledge in medicine and surgery, with a particular emphasis on orthopaedic surgery. We also highlight methods of improving doctor–patient communication and patient knowledge.

Rational molecular design of self- assembling peptide-based materials that spontaneously form self-supporting hydrogels shows potential in many healthcare applications. Binary peptides based on complementary charged sequences are developed, and the use of biophysical analysis and cell-based studies highlights that the charged interactions can influence the properties of peptide materials and ultimately affect biomaterial applications.