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Symposium on ‘The Anatomy of Tissue Engineering’

The winter symposium of the Anatomical Society of Great Britain and Ireland incorporated a symposium entitled ‘The Anatomy of Tissue Engineering’. This symposium volume incorporates the review manuscripts and some original papers emanating from that symposium. The first papers consider the biology of regeneration and how those mechanisms might be harnessed to induce regeneration or to engineer new tissues or organs in the adult. Brockes et al. review the role of the immune response in regeneration and indicate that whilst suppression of some aspects of the immune system facilitates regeneration, other aspects of immune function (e.g. dendritic cells) appear essential to stimulate some elements of the regenerative response. Moreover, regeneration and repair share some common signalling molecules (e.g. thrombin) complement factors and growth factors (e.g. of the TGFβ super family). Continuing the theme of regeneration, Tsonis et al. review the factors involved in lens regeneration and how they might be harnessed for tissue engineering. Finally, Metcalfe et al. review regeneration in the mammal, focusing on the MRL mouse strain, which possesses the ability to completely and perfectly regenerate through and through punch holes to the ear. 
 
Following on the theme of regeneration, the embryonic signals required for bone formation and induction are reviewed by Ripamonti, with a particular focus on experiments conducted in non-human primates. In non-human primates, a number of signalling molecules belonging to the TGFβ super family appear to be able to induce bone formation in a variety of settings: interestingly, different TGFβ family members may act synergistically in bone induction. Continuing the skeletal/embryonic induction theme, Hardingham et al. review the induction of tissue engineered cartilage, particularly focusing on signals provided by the Sox 8 and notch pathways. 
 
The key challenge for all tissue engineered constructs is how to integrate the construct with the host. Archer et al. review this in the context of tissue engineered cartilage. Frequently, failures such as scarring or failure of vascular connection at the interface lead to a poorly functioning or failed tissue engineering construct. 
 
The engineering of specific organs or tissues is considered by Stephan et al. in the context of small-diameter blood vessels. Interestingly, analysis of the interactions of domains of the elastin family members with endothelial and smooth muscle cells has led to a deeper understanding of the vascular cell matrix interactions that are necessary to engineer an appropriately compliant non-thrombogenic vascular tissue engineered construct. In the same tone, Sharpe et al. describe the factors and principals underlying the tissue engineering of teeth for biological replacement. Equally, Kingham et al. consider the scaffold and soluble signals necessary to induce peripheral nerve regeneration following injury. Mansbridge considers the commercial aspects of tissue engineering, including very important issues of scale-up, quality assurance, shelf life, handling, etc., all features that are important in the development of a clinically applicable tissue engineering construct and that are often forgotten at the laboratory experimentation/discovery phase. 
 
Finally, two original papers describe work that was presented as part of the symposium. Wong et al. describe in detail the anatomy of the mouse hind paw digit, with particular focus on the tendons and ligaments. This detailed anatomical description is important for subsequent experiments investigating factors involved in tendon and ligament repair and experimental strategies for enhancing such repair and diminishing adhesions and scarring. Beare et al. describe experiments in the MRL mouse, in which through-and-through punch wounds to the ear regenerate perfectly with the replacement of cartilage, dermis, skin, skin appendages, etc., in a pattern that is indistinguishable from the normal. By contrast, punch wounds made to the dorsal skin of the backs of the same animals do not regenerate and heal with scarring. These observations are important not only in demonstrating that the MRL mouse does not regenerate all of its tissues, but also in indicating that both repair with scarring and perfect tissue regeneration can occur in the same animal at the same time with similar wounds in different tissues. These observations give further strength to the emerging view that only subtle differences in the types, timing or amount of various signalling molecules may underlie the difference between regeneration and repair with scarring. This has important therapeutic implications: pharmacological manipulation of these factors may allow regeneration as opposed to scarring repair in the adult. 
 
This symposium clearly demonstrated how understanding the anatomical principles – tissue structure, inductive signals, cell matrix interactions, immunological interactions, etc. – of embryonic development, regeneration and repair are of the utmost importance in designing novel strategies to enhance regeneration/repair or artificially to engineer tissues for replacement in the adult. Moreover, the integration of these engineered tissues and organs and their appropriate function again requires detailed understanding of the microscopic and molecular anatomy. The commercialization of such knowledge, for patient benefit, requires an integrated multidisciplinary approach combining biomaterials, mathematical modelling, and cellular and molecular biology, together with a detailed understanding of tissue anatomy, physiology and repair. Elucidating the principals underlying tissue development and regeneration and determining how they might be used to regenerate/engineer tissues or organs for the adult is an exciting challenge with great potential for the improvement of human health.