Designer Supersurfaces via Bioinspiration and Biomimetics for Dental Materials and Structures
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The design of surfaces and interfaces gives rise to superior qualities and properties to materials and structures. The interface between biology and materials in nature is being closely examined at the smallest scales for a number of significant reasons. It is recognised that the properties of surfaces have definite biological effects that can be harnessed in clinical regeneration biology. Also the deeper understanding of surface interactions between cells and matrices in human biology is spurring the fabrication of biomimetic and bioinspired versions of these natural designs. The new emerging science of bioinspired surface engineering is helping to improve clinical performances for biomaterials and biostructures because it resolves the problems necessary to optimise integration of implant biomaterials and structures. One of the major developments is the use of surface topography, which is now being exploited for microbial control, steering stem cell behaviours in proliferation and differentiation and adhesive surfaces for better bonding with tissues. In this Chapter we will explore the status of these super surfaces and examine the possibilities for the next generation of dental biomaterials and implants.
KeywordsAntibacterial surfaces Bactericidal surfaces Cell influencing surfaces Microtopography Surface nanotopography
The structural and chemical details at surfaces of biomaterials and the meeting between surfaces is vitally important in the mechanical design of organisms, structural biomaterials, anti-wetting, self-cleaning properties, cell adhesion and migration. These superior and sophisticated properties are what can be termed super surfaces. Evolution has selected for adaptations that include various styles of physical structuring, chemical coatings and molecular patterning to create superior and sophisticated functions at surfaces. These are the best possible adaptations, in the design of surfaces that also apply to the same intrinsic problems faced in applications for biology and medicine. They have been tried, tested and optimized over millions of years of evolution. A result is that many of the adaptations discovered in nature are often new to science and technology. Hence this is the reason why biomimetic based researchers search across nature for new potent ideas in solving materials based problems. There are added advantages in following biomimetic approaches such as, learning how to reduce energy during the construction of materials and features at the surfaces . There are now large catalogues where this kind of innovation information can be easily accessed, interpreted and used for the interrogators problem in hand . An important distinction is to be made between biomimetic and bioinspired approaches. In biomimetics the objective is to simulate or copy a structure, process or mechanism directly from nature. Bioinspiration is the strategy where an influential component from biology is used in the problem solving and its eventual solution. So with bioinspiration there is a confluence of biological and human ingenuity. Each strategy has been used effectively in biomedicine.
In this chapter, we focus on two biomedically significant topics where the design of surfaces can be improved for better clinical outcomes. These topics are bacterial and human cell adhesion and detachment. Specifically, the clinical problem at biomaterial implant surfaces is to drive a strong yet stable biointegration and the second is an effective control of pathogenic microbes at the outer surface of implants. The construction and refinement by optimisation of the surfaces and interfaces of traditional restoration dental materials is a large topic of research but will not be included here. Material scientists are infact still grappling to control these phenomena and having the ability to programme their surfaces to work in tune with biology. The examples we will focus on in this chapter for developing biomedical supersurfaces are mainly studies in bioinspiration.
A major quest for regeneration scientists is the ability to control cell behaviour and activity for a variety of roles. Cell manipulation engineers have achieved some success in defining the mechanisms for influencing cells in predictable ways. Cells are influenced and guided by physical forces and contacts with surfaces. This environment conditions the cells future role. This means that cells in tissue organizing collectives are ultimately programmed outside in than inside out. Considerable research has been underway to develop surface features that can be used to sensitize and direct cell growth, proliferation and differentiation. More advanced surface engineering employs changes in the characteristics of topography, symmetry, geometry, stiffness and elasticity of the underlying material all-together. It has been challenging to systematize all of these elements into cause and effect relationships. The desire is to produce a blueprint for designs that have predicted effects. Programmable biomaterials with influential topography are a realistic prospect for interplay with human cells and bacteria cells. There is tremendous array of data showing the diverse pairings of nanotopography arrays with fibroblasts, endothelial, epithelial, pluripotent, mesenchymal and embryonic [3, 4, 5, 6, 7, 8, 9, 10, 11, 12]. There are numerous instances of conflicting results but there are strong trends emerging. For example, certain topographic structures induce clear differentiation responses within contacting cells. The best example is osteogenesis by Mesenchymal Stem Cells (MSCs) subject to disordered nanopits . Significantly adding to this is evidence of the molecular pathways involved in this process, the main one being integrin-activated focal adhesion kinase (FAK). Another trend is that low aspect ratio structures are favourable to attachment and spreading phenomena whereas higher aspect ratio structures lead to cell sheets that self detach .
Eukaryotic and Prokaryotic cells are also influenced strongly by the chemistry of the surface. The chemistry aspect and the physical features are interlinked. Each influences the downstream effects of the other factor. A surface with a homogenous chemistry on a smooth surface once modified with surface topography redistributes the chemistry and introduces new heterogeneity. In the next section, we map the surfaces and boundaries in and around the tooth organ and describe briefly their biological and mechanical functions.
11.2 Materials Dentistry: A World of Surfaces and Interfaces
In the regenerative sciences precise control of cell proliferation and differentiation is unresolved and therefore remains of considerable future significance. In cell engineering surface structures over large surface areas have been developed to select, maintain, expand and invoke phenotype changes in cell populations with some important successes. Topography at the nanoscale is showing enormous promise as a device to influence cell behaviours in predictable and useful ways for benefits in cell therapy and tissue engineering. Research on surface continues to be a crux in materials dentistry and regenerative dentistry. The major areas would be surfaces for bacteria control and selectivity and surfaces for cell and tissue integration. The basic work on programmed surfaces for cell selection, growth and lineage specification also relate heavily to regenerative dentistry strategies and offer new therapeutic routes. In the next sections of this chapter we hone in on the programmed surfaces with topography for bacteria control, tissue adhesion and biointegration.
11.3 Bactericidal and Antibacterial Surfaces
Bacterial biofilms are notoriously difficult to eradicate from surfaces such as implants. There are different ways of preventing bacteria adhesion and colonisation. The first most extensively investigated is chemical and molecular engineering of surfaces. In these approaches surfaces are built with adjuncts such as dendrimers, cationic peptides, photoactivation, lysostaphin, deactivators of quorum sensing and grafted antibiotics .
In dentistry, there is the added complexity by which the main aim is to selectively control different bacterial populations and not to eradicate everything. The mechanisms of attachment for bacteria are not fully understood. Surface roughness, wettability and surface energy are known to influence bacteria attachment and adhesion most profoundly. The range of limits for these properties has been difficult to measure precisely. Surface roughness above 0.2 μm is known to promote plaque formation. The influence of surface energy properties is complicated by the nature of the bacterial cell wall charge properties. Hydrophobic interactions in bacteria are common since adhesions located on pilli are themselves hydrophobic. According to some evidence acquired in vitro hydrophobic processes drives attachment. However, the greatest task is to unravel the complexities of surface properties and bacteria adhesion in living biological environments. Of greatest prominence is the effect of serum proteins at the surface, which conditions all other biological responses.
11.3.1 Controlling Oral Pathogens via Surface Structuring
The oral cavity is colonised by a whole community of microbes that include bacteria, viruses and fungi. The ecology or interrelationships between the members of the various microbial communities are highly intricate and under constant investigation with new links in the network being uncovered regularly. It is thought that changes in community structure invoke degenerative diseases that cause tissue destruction of dentine, periodontal ligament, gingiva and bone. Once the environment and conditions favour the acceleration of pathogenic growth the disease and tissue destruction is highly likely to occur. Effective ways must be sought to control and eradicate pathogenic microbes from the mouth. A degree of control is often required to reset the community structure of bacteria. There has been voluminous research to effectively kill pathogenic outright. Antibiotics are the most effective altogether. However, there is increasing evolved resistance to antibiotics and the targeted delivery of antibiotics remains imperfect. Other main treatments implement chemical toxins, photodynamic elements and nanoparticles to destroy bacterial biofilms and kill bacteria. There is also renewed interest in prospecting for new antibacterial compounds from sessile invertebrates renowned for the complex defensive chemistry, e.g. Marine sponges and Ascidians. As such there are many examples in nature where evolution has selected for sophisticated adaptations to kill microbes or prevent contact with the organism. A significant adaptation that has emerged is structural devices at surfaces.
The structure consists of nanometric pillars 200 nm tall, 100 nm in diameter at the base and 60 nm at the tip spaced 170 nm apart in a highly regular and tight pattern. This precision piece of Nano architecture being ten times smaller than the cell itself punctured settling bacterial cells and killed them with 60 min from attachment (Fig. 11.2). The killing power has been measured for this wing surface and was described as being efficient with 6 × 106 bacterial cells made inoperable in every square centimeter after 30 min . These initial results represent are of supreme usefulness for control of clinical infections anchored onto biomaterial and implant surfaces. However, the topography did not kill gram-positive species of bacteria: B. subtilis, P. maritimus, and S. aureus species of bacteria. Other wing topographies are being actively pursued as potential antibacterial and bactericidal devices. It has been reported that Dragonfly wings Diplacodes bipunctata have strong and rapid bactericidal effects on a broader range of bacteria classes-both gram negative and gram-positive types as well as bacterial spores. A synthetically created surface with the exact same features of densely packed protruding nanospikes as the Dragonfly wing demonstrated the same bactericidal effects. It was estimated that 45,000 bacterial cells every minute in every cm squared were killed. Black silicon is this equivalent and is generated using ion beam technology. This is costly and cannot be transferred onto just any surface and specifically onto the type of materials useful in biomedicine .
Surface roughness and structure influences human cells more acutely than bacterial cells. This is because eukaryotic cells have a much more complicated sensory apparatus than prokaryotes. It was first evidenced that human cells can sense, detect and “react” to structures of >5 nm at very small distances of 3–15 nm . Physical attachments between cells and extracellular matrix (ECM) molecules can only be made at such close distance. There is broad remit to harness the sensory apparatus of the cell and influence their behaviour in many important aspects such as, migration, alignment, polarity, differentiation and proliferation. Such governability opens up many biotechnological and therapeutic avenues from tissue regeneration to biosensing.
11.4 Cell Adhesive Surfaces Using Nanotopography
11.5 Tissue Adhesive Surfaces
Materials with surfaces that can adhere to living tissue and participate in regeneration, development and repair are important. In surgery tough, stretchable and tear resistant tapes able to stick rigidly to tissues would be broadly revolutionary in the treatment of wounds, reducing surgery and complications. Conceivably such a design could be used to replace sutures and staples. Bioglues have been developed as potential candidates for wound closure and sealing. However, they have been dogged by inflammation susceptibility. The reason is that the toughening of these tissue adhesives requires strong chemical reactions to take place, and is the source of biological irritation. Another point is to develop effective glues that bond in wet conditions. In both cases natural ingenuity may offer prospects for success. Adhesives derived from nature may offer a chemistry of bonding which is more favourable to biological systems and less inflammatory. In this vein, analogues (e.g. polydopamine) of the main active ingredient of mussel adhesive proteins, 3,4-dihydroxyphenylalanine (DOPA) have been broadly investigated.
11.6 Surfaces for Cell Proliferation and Differentiation
Structures at surfaces that elicit proliferation and/or differentiation responses are in high demand especially those with high potency and precise reactions [11, 12]. A principal property of the surface with biological implications is wettability feature . Still more information is needed to completely understand the effects of wettability on cell attachment and tissue integration. Surprisingly for dental implants the wettability is usually not measured or considered in biological evaluation. The topic has been scrutinised most widely for implant osseointegration . Generally wettabilities of intermediate values can optimise favourable cell interactions. An important contribution of wettability to biodynamics at the surface is protein adsorption. Proteins are the first biomolecule to arrive at the surface taking milliseconds. The nature of the protein assembly at the surface directs the cell response. This has been studied mainly with osteoblasts as well as fibroblasts and keratinocytes. Synergism between topography and chemical properties occurs but the interrelationship is unpredictable.
One of the purposes is to discover and develop the most efficient platform of expanding the numbers of stem cells in vitro into the population numbers needed for therapeutic tissue regeneration. In addition the ability to specify cell lineages of the expanded populations is another necessity to generate desired tissue types. Once again platform cell-scale microgauged technologies that can achieve this accurately and with high specificity are still needed. These base technologies are useful for the study of basic processes and in modelling responses to new drugs and to build phenotypically accurate populations of cells for tissue regeneration. Much work has been carried out to unravel the mechanisms involved in surface contact and gene expression. The principal contact point is the subcellular macromolecular focal adhesion, which is joined between the cell cytoskeleton and extracellular matrices . The association and clustering of these objects with the matrix is an important effect that allows sensing of mechanical forces. Others have discovered the molecular circuits directly involved in transmitting topography influences into the cell nucleus where it impinges on gene expression patterns.
The interplay between cells and surfaces directs the future activity and behaviour of the contacting cell population. This interaction can be designed or programmed by physical and chemical patterning using sophisticated machines. Originally the patterning geometries did not have equivalents in biological systems. Increasingly cell engineering via surfaces is being lead by mimicking the patterned features on ECM supramolecules and other structures. The physical characteristics used to influence cells on contact include: topography, stiffness and elasticity. A lot of promising results have emerged through the different shaping of nanotopography, which cells can sense. We interpret this sensing feature to result from adaptations to sense features of extracellular matrices that are constructed from nanogauge objects and display nanofeatures in the final ECM product. We highlighted how nanotopography is helping to control bacteria populations and to stimulate stem and pluripotent cells into deliberate actions using natural Cicada wing structures. Construction of a systematic order is needed to connect a feature by shape or dimension with a single or collective response by a cell. We also highlighted the utility of topography design on the physical attachment and biointegration with different tissues. In one instance a group of bioengineers successfully demonstrated the strong tissue attachment of a polymer membrane patterned with nanopillars, and augmented with oxidised dextran, but inspired from the structure and adhesive properties of small hairs on the Gecko footpad. Thus, bioinspiration methodology could be the guide for the next design of plaster for wound healing inside the oral cavity. Biomimetic and bioinspired nanotopographies mined from nature are largely unexplored in these areas of dentistry.
We thank our lab members both Oral Biosciences at HKU and Jung's lab at YUCD for helpful discussion and comments on the manuscript.
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