The interface between implanted devices and their host tissue is complex and is often optimized for maximal integration and cell adhesion. However, this also gives a surface suitable for bacterial colonization. We have developed a novel method of modifying the surface at the material-tissue interface with an antimicrobial peptide (AMP) coating to allow cell attachment while inhibiting bacterial colonization. The technology reported here is a dual AMP coating. The dual coating consists of AMPs covalently bonded to the hydroxyapatite surface, followed by deposition of electrostatically bound AMPs. The dual approach gives an efficacious coating which is stable for over 12 months and can prevent colonization of the surface by both Gram-positive and Gram-negative bacteria.
Inorganic cements have found utility in tissue replacement since the late nineteenth century, one of the first examples being calcium sulphates in the augmentation of bone defects. In the intervening period of time countless formulations of calcium phosphate, sulphate and silicate cement have been researched and as a result, many are now commercially available for a variety of biomedical applications. This review summarises the applications, formulations, advantages and drawbacks of such inorganic cements, suggesting future work that will drive progress in this area into the future of biomaterials research.
Calcium phosphate (CaPO) tubes with features comparable to mineralized biological microstructures, such as Haversian canals, were grown from a calcium gel/phosphate solution chemical garden system. A significant difference in gel mass in response to high and low solute phosphate equivalent environments existed within 30 min of solution layering upon gel (p = 0.0067), suggesting that the nature of advective movement between gel and solution is dependent on the solution concentration. The transport of calcium cations (Ca) and phosphate anions (PO) was quantified and changes in pH were monitored to explain the preferential formation of tubes within a PO concentration range of 0.5-1.25 M. Ingress from the anionic solution phase into the gel followed by the liberation of Ca ions from the gel was found to be essential for acquiring self-assembled tubular CaPO structures. Tube analysis by scanning electron microscopy (SEM), X-ray diffraction (XRD), and micro X-ray florescence (μ-XRF) revealed hydroxyapatite (HA, Ca(PO)(OH)) and dicalcium phosphate dihydrate (DCPD, CaHPO·2HO) phases organized in a hierarchical manner. Notably, the tubule diameters ranged from 100 to 150 μm, an ideal size for the permeation of vasculature in biological hard tissue.
Bone is a highly responsive organ, which continuously adapts to the environment it is subjected to in order to withstand metabolic demands. These events are difficult to study in this particular tissue in vivo, due to its rigid, mineralised structure and inaccessibility of the cellular component located within. This manuscript presents the development of a micron-scale bone organoid prototype, a concept that can allow the study of bone processes at the cell-tissue interface. The model is constructed with a combination of primary female osteoblastic and osteoclastic cells, seeded onto femoral head micro-trabeculae, where they recapitulate relevant phenotypes and functions. Subsequently, constructs are inserted into a simulated microgravity bioreactor (NASA-Synthecon) to model a pathological state of reduced mechanical stimulation. In these constructs, we detected osteoclastic bone resorption sites, which were different in morphology in the simulated microgravity group compared to static controls. Once encapsulated in human fibrin and exposed to analogue microgravity for 5 days, masses of bone can be observed being lost from the initial structure, allowing to simulate the bone loss process further. Constructs can function as multicellular, organotypic units. Large osteocytic projections and tubular structures develop from the initial construct into the matrix at the millimetre scale. Micron-level fragments from the initial bone structure are detected travelling along these tubules and carried to sites distant from the native structure, where new matrix formation is initiated. We believe this model allows the study of fine-level physiological processes, which can shed light into pathological bone loss and imbalances in bone remodelling.
A diverse range of complex patterns and mineralised hierarchical microstructures can be derived from chemobrionic systems. In this work, we explore chemobrionic calcium phosphate tubes as cellular scaffolds.
Various injectable biomaterials are developed for the minimally invasive delivery of therapeutics. Typically, a mechanical tester is used to ascertain the force required to inject these biomaterials through a given syringe‐needle system. However, currently there is no method to correlate the force measured in the laboratory to the perceived effort required to perform that injection by the end user. In this article, the injection force (F) for a variety of biomaterials, displaying a range of rheological properties, is compared with the effort scores from a 50 person panel study. The maximum injection force measured at crosshead speed 1 mm s−1 is a good proxy for injection effort, with an R2 of 0.89. This correlation leads to the following conclusions: participants can easily inject 5 mL of substance for F < 12 N; considerable effort is required to inject 5 mL for 12 N < F < 38 N; great effort is required and <5 mL can be injected for 38 N < F < 64 N; and materials are entirely non‐injectable for F > 64 N. These values may be used by developers of injectable biomaterials to make decisions about formulations and needle sizes early in the translational process.
Chemical gardens are an example of a chemobrionic system that typically result in abiotic macro-, micro- and nano- material architectures, with formation driven by complex out-of-equilibrium reaction mechanisms. From a technological perspective, controlling chemobrionic processes may hold great promise for the creation of novel, compositionally diverse and ultimately, useful materials and devices. In this work, we engineer an innovative custom-built liquid exchange unit that enables us to control the formation of tubular chemical garden structures grown from the interface between calcium loaded hydrogel and phosphate solution. We show that systematic displacement of phosphate solution with water (H2O) can halt self-assembly, precisely control tube height and purify structures in situ. Furthermore, we demonstrate the fabrication of a heterogeneous chemobrionic composite material composed of aligned, high-aspect ratio calcium phosphate channels running through an otherwise dense matrix of poly(2-hydroxyethyl methacrylate) (pHEMA). Given that the principles we derive can be broadly applied to potentially control various chemobrionic systems, this work paves the way for fabricating multifunctional materials that may hold great potential in a variety of application areas, such as regenerative medicine, catalysis and microfluidics.
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