PADOVA STUDY CLUB

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BONE TISSUE REMODELING  I think we should reconsider the dynamics of bone/tissue remodeling and how signal-proteins are involved in this process. Referring to the current knowledge of bone/tissue biology there are only a few facts that we know:   1. growth of tissue requires cell division   2. properties of the daughter cell need to be identical to the mother cell, otherwise the resulting tissue would loose its original properties   3. these properties of a cell are in accordance with its location and function (cornea, heart, bone, pancreas, liver, connective tissue...) ,and are "frozen" within its DNA   4. during cell cycle the DNA doubles and thus ensures the transfer of the properties   5. to initiate cell division especially during healing, the cells need certain proteins, called cytokines of the injured cell, which are being released by the content spill on the occasion of the injury   6. these cytokines need specific receptors on the target cell to initiate its accelerated cell division   7. a cell of a different tissue does not provide these specific receptors thus avoiding an increased cell division of a non-injured tissue/cell, that doesn't need healing   8. in transplanting tissue pieces to a different location even within an individual body, the target environment does not match the receptor-system for the cytokines of the injured cells of the transplant (the reason for kidney rejection)   9. in exchanging bone pieces from the hip, the mandible or the maxilla, the miss-match of the receptors and the cytokines of the source and the target environment leads to a stop of the cell cycle, ultimately of the healing process   10. in accordance with its embryologic origin of the neural crest tube (a very early stage of development) there are three different bone types with different cytokine/receptor systems:   a. skull with the maxilla (forebrain) b. mandible (midbrain) c. skeleton (hindbrain)   11. there are numerous natural blocking membranes which avoid unintentional mixing of tissue-specific signal-proteins like cytokines: e.g. dura mater, pericardium, kidney capsule, pleura and so on   12. in bone this is the periosteum   13. the denudation of periosteum not only leads to swelling because the fluid comes out (kind of 'leaking'), but also to the development of a new blocking 'membrane', a new periosteum as a result of the competing cytokines of the soft tissue and the bone.   14. an artificial blocking membrane inhibits this competition.   In principle this is it. Of course it’s more complicated than described here, only my humble list. For those who are interested in further reading I may refer to the textbook of Bruce Alberts: The Molecular Biology Of The Cell, 4th Ed., and with regard to the origin of the bone types to Helms, J.A. et al. and their review article in Nature 423, 2003; abstract available at Medline.   I agree with the suggestion of using a blocking membrane. This membrane separates the signal proteins of the soft tissue from those of the original bone site. It enables an undisturbed regeneration of the bone tissue within its own encysted environment. However, the role of the bone transplant is reduced to being a space-holder. This piece will never be integrated as bone. In contrast it will be disintegrated into resorbable components by means of MMP’s, other enzymes and enzyme-catalysed addition of water (hydrolysis) as every biologic/synthetic (TCP and HP) foreign substance will be. Depending on the amount of its volume this process takes a more or less long time (app. 1-2 years). As to your question for anything different: your first intention was to place too big an implant into a too narrow bone. Instead of trying to adjust the bone to the implant you may circumnavigate these futile surgical attempts (imagine the effort of a hip bone transplant) and the disappointment for you and your patient in switching to a different implant that fits into the available bone in the first place.   Questions are welcome.   ===============================