Pamela Walsh

Designs from the deep: marine organisms for bone tissue engineering.

Current strategies for bone repair have accepted limitations and the search for synthetic graft materials or for scaffolds that will support ex vivo bone tissue engineering continues. Biomimetic strategies have led to the investigation of naturally occurring porous structures as templates for bone growth. The marine environment is rich in mineralizing organisms with porous structures, some of which are currently being used as bone graft materials and others that are in early stages of development. This review describes the current evidence available for these organisms, considers the relative promise of each and suggests potential future directions.

Marine organisms for bone repair and regeneration

Abstract: Bioprospecting has led to increased interest in potential applications for marine organisms and their by-products. As a rich source of mineralising porous organisms, our seas and oceans could provide new directions for bone tissue engineering, particularly in the supply of biomimetic templates that may enhance in vivo and ex vivo bone formation. In this chapter we examine the history of marine organism use in this field; exploring how these organisms could be utilised, given the problems of sustainability, and reviewing the current evidence to support their use for bone repair and regeneration.

Exploratory Testing of Diatom Silica to Map the Role of Material Attributes on Cell Fate

Porous silica is an attractive biomaterial in many applications, including drug-delivery systems, bone-graft fillers and medical devices. The issue with porous silica biomaterials is the rate at which they resorb and the significant role played by interfacial chemistry on the host response in vivo. This paper explores the potential of diatom-biosilica as a model tool to assist in the task of mapping and quantifying the role of surface topography and chemical cues on cell fate. Diatoms are unicellular microalgae whose cell walls are composed of, amorphous nanopatterned biosilica that cannot be replicated synthetically. Their unique nanotopography has the potential to improve understanding of interface reactions between materials and cells. This study used Cyclotella meneghiniana as a test subject to assess cytotoxicity and pro-inflammatory reactions to diatom-biosilica. The results suggest that diatom-biosilica is non-cytotoxic to J774.2 macrophage cells, and supports cell proliferation and growth. The addition of amine and thiol linkers have shown a significant effect on cytotoxicity, growth and cytokine response, thus warranting further investigation into the interfacial effects of small chemical modifications to substrate surfaces. The overall findings suggest diatom-biosilica offers a unique platform for in-depth investigation of the role played by nanotopography and chemistry in biomedical applications.

A study of the relationship between process conditions and mechanical strength of mineralized red algae in the preparation of a marine-derived bone void filler

Bone void fillers that can enhance biological function to augment skeletal repair have significant therapeutic potential in bone replacement surgery. This work focuses on the development of a unique microporous (0.5–10 µm) marine-derived calcium phosphate bioceramic granule. It was prepared from Corallina officinalis, a mineralized red alga, using a novel manufacturing process. This involved thermal processing, followed by a low pressure-temperature chemical synthesis reaction. The study found that the ability to maintain the unique algal morphology was dependent on the thermal processing conditions. This study investigates the effect of thermal heat treatment on the physiochemical properties of the alga. Thermogravi-metric analysis was used to monitor its thermal decomposition. The resultant thermograms indicated the presence of a residual organic phase at temperatures below 500°C and an irreversible solid-state phase transition from mg-rich-calcite to calcium oxide at temperatures over 850°C. Algae and synthetic calcite were evaluated following heat treatment in an air-circulating furnace at temperatures ranging from 400 to 800°C. The highest levels of mass loss occurred between 400–500°C and 700–800°C, which were attributed to the organic and carbonate decomposition respectively. The changes in mechanical strength were quantified using a simple mechanical test, which measured the bulk compressive strength of the algae. The mechanical test used may provide a useful evaluation of the compressive properties of similar bone void fillers that are in granular form. The study concluded that soak temperatures in the range of 600 to 700°C provided the optimum physiochemical properties as a precursor to conversion to hydroxyapatite (HA). At these temperatures, a partial phase transition to calcium oxide occurred and the original skeletal morphology of the alga remained intact.

Blueprints for the Next Generation of Bioinspired and Biomimetic Mineralised Composites for Bone Regeneration

Coccolithophores are unicellular marine phytoplankton, which produce intricate, tightly regulated, exoskeleton calcite structures. The formation of biogenic calcite occurs either intracellularly, forming ‘wheel-like’ calcite plates, or extracellularly, forming ‘tiled-like’ plates known as coccoliths. Secreted coccoliths then self-assemble into multiple layers to form the coccosphere, creating a protective wall around the organism. The cell wall hosts a variety of unique species-specific inorganic morphologies that cannot be replicated synthetically. Although biomineralisation has been extensively studied, it is still not fully understood. It is becoming more apparent that biologically controlled mineralisation is still an elusive goal. A key question to address is how nature goes from basic building blocks to the ultrafine, highly organised structures found in coccolithophores. A better understanding of coccolithophore biomineralisation will offer new insight into biomimetic and bioinspired synthesis of advanced, functionalised materials for bone tissue regeneration. The purpose of this review is to spark new interest in biomineralisation and gain new insight into coccolithophores from a material science perspective, drawing on existing knowledge from taxonomists, geologists, palaeontologists and phycologists.

An in vitro Study to Assess the Potential of a Unique Micro porous Algal Derived Cap Bone Void Filler in Comparison with Clinically-Used Bone Void Fillers

Macroporosity(>100?m) in bone void fillers is a known prerequisite for tissue regeneration, but recent literature has highlighted the added benefit of microporosity(0.5 - 10?m). The aim of this study was to compare the in vitro performances of a novel interconnective microporous hydroxyapatite (HA) derived from red algae to four clinically available macroporous calcium phosphate (CaP) bone void fillers. The use of algae as a starting material for this novel void filler overcomes the issue of sustainability, which overshadows continued use of scleractinian coral in the production of some commercially available materials, namely Pro-Osteon TM and Bio-Coral ® . This study investigated the physicochemical properties of each bone voidfiller material using x-ray diffraction, fourier transform infrared spectroscopy, inductive coupled plasma, and nitrogen gas absorption and mercury porosimetry. Biochemical analysis, XTT, picogreen and alkaline phosphatase assays were used to evaluate the biological performances of the five materials. Results showed that algal HA is non-toxic to human foetal osteoblast (hFOB) cells and supports cell proliferation and differentiation. The preliminary in vitro testing of microporous algal-HA suggests that it is comparable to the four clinically approved macroporous bone void fillers tested. The results demonstrate that microporous algal HA has good potential for use in vivo and in new tissue engineered strategies for hard tissue repair.