This review gives an updated overview on keratinocyte transplantation in burn wounds concentrating on application methods and future therapeutic cell delivery options with a special interest in ...hydrogels and spray devices for cell delivery.
To achieve faster re-epithelialisation of burn wounds, the original autologous keratinocyte culture and transplantation technique was introduced over 3 decades ago. Application types of keratinocytes transplantation have improved from cell sheets to single-cell solutions delivered with a spray system. However, further enhancement of cell culture, cell viability and function in vivo, cell carrier and cell delivery systems remain themes of interest.
Hydrogels such as chitosan, alginate, fibrin and collagen are frequently used in burn wound care and have advantageous characteristics as cell carriers.
Future approaches of keratinocyte transplantation involve spray devices, but optimisation of application technique and carrier type is necessary.
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Magnesium oxychloride cement (MOC) has been used in civil engineering for more than 100years, but its application has been limited by its poor water resistance. This property, however, could be ...exploited in the formulation of a resorbable orthopaedic biomaterial. In this study, H3PO4 was added to control the degradation process of MOC to provide a predictable and clinically appropriate resorption time. The effects of H3PO4 on the phases, microstructures, mechanical properties, hydration and degradation of MOC have been evaluated. The results revealed that the crystalline phases in MOC before and after adding H3PO4 were the same, but that the needle-like phase 5 (5Mg(OH)2·MgCl2·8H2O) crystals were formed more extensively in MOC with H3PO4 than that in MOC without H3PO4. Furthermore, the addition of H3PO4 was shown to retard the hydration process. H3PO4 did significantly improve the water resistance of MOC though its addition resulting in a reduction in compressive strength.
There have been a number of recently reported approaches for the manufacture of complex 3D printed cell‐containing hydrogels. Given the fragility of the parts during manufacturing, the most ...successful approaches use a supportive particulate gel bed and have enabled the production of complex gel structures previously unattainable using other 3D printing methods. The supporting gel bed provides protection to the fragile printed part during the printing process, preventing the structure from collapsing under its own weight prior to crosslinking. Despite the apparent similarity of the particulate beds, the way the particles are manufactured strongly influences how they interact with one another and the part during fabrication, with implications to the quality of the final product. Recently, the process of suspended layer additive manufacture (SLAM) is demonstrated to create a structure that recapitulated the osteochondral region by printing into an agarose particulate gel. The manufacturing process for this gel (the application of shear during gelation) produced a self‐healing gel with rapid recovery of its elastic properties following disruption. Here, the physical characteristics of the supporting fluid‐gel matrix used in SLAM are explored, and compared to other particulate gel supporting beds, highlighting its potential for producing complex hydrogel‐based parts.
Shear caused by passage of the needle through a fluid‐gel support bed causes thinning, which allows deposition of a secondary gel. Subsequent rapid recovery in viscosity and elastic properties enables the bed to support the formation of a complex gel structure. The process is gentle enough to allow cell deposition.
Advances in bioprinting have enabled the fabrication of complex tissue constructs with high speed and resolution. However, there remains significant structural and biological complexity within ...tissues that bioprinting is unable to recapitulate. Bone, for example, has a hierarchical organization ranging from the molecular to whole organ level. Current bioprinting techniques and the materials employed have imposed limits on the scale, speed, and resolution that can be achieved, rendering the technique unable to reproduce the structural hierarchies and cell–matrix interactions that are observed in bone. The shift toward biomimetic approaches in bone tissue engineering, where hydrogels provide biophysical and biochemical cues to encapsulated cells, is a promising approach to enhancing the biological function and development of tissues for in vitro modeling. A major focus in bioprinting of bone tissue for in vitro modeling is creating dynamic microenvironmental niches to support, stimulate, and direct the cellular processes for bone formation and remodeling. Hydrogels are ideal materials for imitating the extracellular matrix since they can be engineered to present various cues whilst allowing bioprinting. Here, recent advances in hydrogels and 3D bioprinting toward creating a microenvironmental niche that is conducive to tissue engineering of in vitro models of bone are reviewed.
This review focuses on hydrogels and 3D bioprinting in bone tissue engineering for development of in vitro models of bone. It highlights challenges in recapitulating the biological complexity seen in bone and how synergistic application of dynamic hydrogels and innovative bioprinting pipelines can address these challenges to achieve bone models.
One of the main challenges in additive manufacturing (AM) of medical implants for the treatment of bone tissue defects is to optimise the mechanical and biological performance. The use of ...post-processing can be a necessity to improve the physical properties of customised AM processed implants. In this study, Ti-6Al-4V coupons were manufactured using selective laser melting (SLM) in two build orientations (vertical and horizontal) and subsequently post-processed using combinations of hot isostatic pressing (HIP), sandblasting (SB), polishing (PL) and chemical etching (CE). The effect of the different post-manufacturing strategies on the tensile and fatigue performance of the SLMed parts was investigated and rationalised by observing the surface topography. Vertically built samples showed higher yield strength (YS) and ultimate tensile strength (UTS) than the horizontal samples, increasing from 760.9 ± 22.3 MPa and 961.3 ± 50.2 MPa in the horizontal condition to 820.09 ± 16.5 MPa and 1006.7 ± 6.3 MPa in the vertical condition, respectively. After the HIP treatment, the ductility was substantially improved in both orientations; by 2.1 and 2.9 folds in the vertical and horizontal orientations, respectively. The vertically built samples demonstrated a superior ductility of 22% following HIP and polishing. Furthermore, chemical etching was found to be the most effective surface post-processing treatment to improve the fatigue performance after HIP, achieving the highest run-out strength of 450 MPa. Most importantly, chemical etching after HIP enhanced the cellular affinity of the surface, in addition to its good fatigue performance, making it a promising post-processing approach for bone implants where tissue integration is needed.
There has been a consistent increase in the mean life expectancy of the population of the developed world over the past century. Healthy life expectancy, however, has not increased concurrently. As a ...result we are living a larger proportion of our lives in poor health and there is a growing demand for the replacement of diseased and damaged tissues. While traditionally tissue grafts have functioned well for this purpose, the demand for tissue grafts now exceeds the supply. For this reason, research in regenerative medicine is rapidly expanding to cope with this new demand. There is now a trend towards supplying cells with a material in order to expedite the tissue healing process. Hydrogel encapsulation provides cells with a three dimensional environment similar to that experienced in vivo and therefore may allow the maintenance of normal cellular function in order to produce tissues similar to those found in the body. In this review we discuss biopolymeric gels that have been used for the encapsulation of mammalian cells for tissue engineering applications as well as a brief overview of cell encapsulation for therapeutic protein production. This review focuses on agarose, alginate, collagen, fibrin, hyaluronic acid and gelatin since they are widely used for cell encapsulation. The literature on the regeneration of cartilage, bone, ligament, tendon, skin, blood vessels and neural tissues using these materials has been summarised.
Airborne pathogens pose high risks in terms of both contraction and transmission within the respiratory pathways, particularly the nasal region. However, there is little in the way of adequate ...intervention that can protect an individual or prevent further spread. This study reports on a nasal formulation with the capacity to combat such challenges, focusing on severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). Formulation of a polysaccharide‐based spray, known for its mucoadhesive properties, is undertaken and it is characterized for its mechanical, spray distribution, and antiviral properties. The ability to engineer key mechanical characteristics such as dynamic yield stresses and high coverage is shown, through systematic understanding of the composite mixture containing both gellan and λ‐carrageenan. Furthermore, the spray systems demonstrate highly potent capacities to prevent SARS‐CoV‐2 infection in Vero cells, resulting in complete inhibition when either treating, the cells, or the virus, prior to challenging for infection. From this data, a mechanism for both prophylaxis and prevention is proposed; where entrapment within a polymeric coating sterically blocks virus uptake into the cells, inactivating the virus, and allowing clearance within the viscous medium. As such, a fully preventative spray is formulated, targeted at protecting the lining of the upper respiratory pathways against SARS‐CoV‐2.
There is a high risk of transmission of airborne pathogens through the nasal epithelium. This study reports a novel nasal spray, which is designed to maximize surface coverage and prevent infection through physical entrapment and inhibition of infection by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2).
Alginate hydrogels are commonly used in biomedical applications such as scaffolds for tissue engineering, drug delivery, and as a medium for cell immobilisation. Multivalent cations are often ...employed to create physical crosslinks between carboxyl and hydroxyl moieties on neighbouring polysaccharide chains, creating hydrogels with a range of mechanical properties. This work describes the manufacture and characterisation of sodium alginate hydrogels using the divalent cations Mg2+, Ca2+ and Sr2+ to promote gelation via non-covalent crosslinks. Gelation time and Young׳s modulus are characterised as a function of cation and alginate concentrations. The implications of this work towards the use of environmental elasticity to control stem cell differentiation are discussed.
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•Manufacture of sodium alginate hydrogels using divalent cations.•Force–displacement data measured using spherical indentation.•Gelation time and Young׳s modulus as a function of cation and polymer concentration.•Young׳s modulus and rate of gelation scaled according to Ca2+>Sr2+>Mg2+.•Hydrogel moduli in the range 150–550kPa were achieved.
A method for the production of complex cell‐laden structures is reported, which allows high‐levels of spatial control over mechanical and chemical properties. The potential of this method for ...producing complicated tissues is demonstrated by manufacturing a complex hard/soft tissue interface and demonstrating that cell phenotype can be maintained over four weeks of culture.
The development of new materials for clinical use is limited by an onerous regulatory framework, which means that taking a completely new material into the clinic can make translation economically ...unfeasible. One way to get around this issue is to structure materials that are already approved by the regulator, such that they exhibit very distinct physical properties and can be used in a broader range of clinical applications. Here, the focus is on the structuring of soft materials at multiple length scales by modifying processing conditions. By applying shear to newly forming materials, it is possible to trigger molecular reorganization of polymer chains, such that they aggregate to form particles and ribbon‐like structures. These structures then weakly interact at zero shear forming a solid‐like material. The resulting self‐healing network is of particular use for a range of different biomedical applications. How these materials are used to allow the delivery of therapeutic entities (cells and proteins) and as a support for additive layer manufacturing of larger‐scale tissue constructs is discussed. This technology enables the development of a range of novel materials and structures for tissue augmentation and regeneration.
Structured soft materials have the potential to revolutionize regenerative medicine. By imparting shear during processing, it is possible to take the small number of materials approved by medical regulators and create self‐healing polymeric structures. How so‐called fluid gels can facilitate the delivery of cells and proteins and enable additive layer manufacturing of complex biological structures is discussed.
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