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11.1 What are the advantages and disadvantages of synthetic, auto, and allografts?
The key disadvantages of using synthetic materials for grafts is that they tend to be thrombogenic, do not integrate with recipient tissue and are more prone to infection. This is counterbalanced by convenience (theoretically available in unlimited quantities to precise specifications) and the fact that they can be supplied sterile with no risk of donor-recipient disease transmission. Allografts address some of these deficiencies in that they are of biological origin, hence integrate more effectively and are more resistant to infection, but are (in some cases) limited in availability and carry a perceived risk of donor to recipient disease transmission. Autografts are the ‘gold standard’ with respect to tissue grafts as they carry no risk of disease transmission, do not provoke an immune response and can actively promote healing through the co-grafting of autologous cells with the tissue. The key disadvantage with autografts is donor site morbidity, and limited or no availability (for example limited amounts of bone autograft can be taken from the iliac crest, at the expense of a second operation site to harvest the graft, but for other tissues, e.g. eye cornea, autografting is not an option, as we are effectively ‘robbing Peter to pay Paul’)
11.2 What is the role (in the UK) of the HTA?
The HTA is a watchdog that licenses and inspects tissue banks. It enforces the UK Human Tissue Act (2004) and is the competent body in the UK for ensuring compliance with the European Cell and Tissue Directive. It issues guidance, policies, and codes of practice with which tissue banks must comply
11.3 What steps are taken when retrieving tissues to reduce the risk of bacterial contamination?
Tissue retrieval takes place as soon as possible post mortem. With minimal warm ischaemia it takes place mostly in hospital mortuaries when no other routine mortuary activities are taking place. Prior to retrieval, the donor is cleaned using surgical disinfectants. Retrieval staff wear surgical gowns and utilize sterile, single-use instrumentation throughout the retrieval process. Any equipment that must be re-used (dermatomes, surgical saws) is sterilized in between uses. Retrieved tissue is sealed in sterile bags and placed on wet ice immediately following retrieval.
11.4 What are the three main reasons for processing tissues? Briefly outline the two methods commonly used to preserve tissues.
To improve clinical efficacy, make them safer, and to permit long-term storage. The two most commonly used methods are lyophilization (drying the tissue at low temperature under a vacuum) and low temperature reservation, either by deep freezing for non-viable tissues, or cryopreservation where viability is desirable.
11.5 How is bone processed and stored?
The bone is dissected to remove adherent soft tissues and cut and/or ground to its required specification. It is then marrow depleted, using warm water washing, chemical washing (to remove lipid components of the marrow), and centrifugation to physically remove the marrow from the bone. The efficacy of these processed is enhanced by applying them at elevated temperatures (up to 60°C) to soften the marrow components and enhance their solubility in the washing fluids. It is then freeze dried or frozen for longterm storage, and may be terminally sterilized with irradiation. Freeze dried bone is stored at ambient temperature, frozen bone at low (-80°C) temperature. Frozen bone may be stored at higher temperatures (up to -20°C), but its expiry date will be reduced.
11.6 What are the advantages and disadvantages of xeno-, auto-, and allografts, and synthetic grafts?
Xenografts can be widely available especially with the emergence of transgenic animals, however a significant disadvantage is their rejection as they present a multitude of different antigens to the host. The xenograft (unless genetically modified) also does not functionally respond to complement and produce human hormones and/or growth factors. Autografts have the advantage that they are perfectly matched to the host, but clearly are not appropriate for certain grafts (for example heart and lungs) as they may be damaged beyond their functionality. Allografts are extremely useful in that they may induce some graft versus tumour effects, which is effective in the destruction of liquid tumours (e.g. leukemia) but graft versus host effects where the graft is not well matched can be life threatening. Allografts almost invariably require some degree of immunosuppression.