Practical Transfusion Medicine 4th Ed.

44. Tissue banking

Akila Chandrasekar, Paul Rooney & John Kearney

NHS Blood and Transplant Tissue Services, Liverpool, UK

Regulation

The European Union Tissue and Cells Directives (EUTCD) set a benchmark for the standards that must be met when carrying out any activity involving tissues and cells for human application (patient treatment) by all member states. The EUTCD is made up of three Directives, the parent Directive (2004/23/EC), which provides the framework legislation, and two technical directives (2006/17/EC and 2006/86/EC), which provide the detailed requirements of the EUTCD.

The Human Tissue Act (2004) established the Human Tissue Authority (HTA) as the competent authority, with the responsibility for regulating tissues and cells (other than gametes and embryos) for human application within England, Wales and Northern Ireland. There is separate legislation in Scotland - the Human Tissue (Scotland) Act 2006 – with a high degree of similarity between both acts. The EU Directives were fully implemented into UK law in 2007, via the Human Tissue (Quality and Safety for Human Application) Regulations 2007. The HTA codes of practice provide guidance and lay down expected standards for the sectors regulated by the organization. The revised codes, effective since 2009, are designed to support professionals with advice and guidance based on real-life experience. More information is available at http://www.hta.gov.uk.

Tissue banks in the USA are regulated by the Food and Drug Administration (FDA) with standards set by the American Association of Tissue Banks (AATB).

Consent

Consent is the fundamental principle of the Human Tissue Act and underpins the lawful removal, storage and the use of donated tissue for any purpose. The Act provides for financial and custodial penalties for breaches of its requirements. While provisions of the Human Tissue (Scotland) Act 2006 are based on authorization rather than consent, these are essentially both expressions of the same principle. In Europe, the legal requirements for obtaining permission for retrieval of tissues after death vary from country to country [1]. However, even where ‘opting out’ or ‘presumed consent’ systems are operated, it is considered best professional practice to confirm that no relatives object to the donation proceeding.

To ensure that tissue donation for any purpose, either for clinical use or research purposes, is lawful, informed and valid consent must be obtained from an appropriate person, prior to tissue retrieval. Different consent requirements apply when dealing with tissue from deceased and living donors. With a living donor, the appropriate person is generally the donor themselves. For deceased donors, this can be the wishes of the deceased themselves expressed in life, e.g. through the organ donor register, or their nominated representative, a person who was appointed in life by the deceased to make these decisions. In the absence of either of these, the consent of a person in a ‘qualifying relationship’ with them immediately before they died must be sought. This may be (in order of priority) a spouse or partner, blood relation or friend.

Consent must be given voluntarily. It is also important that the person giving consent is fully informed about all aspects of the donation process and, where appropriate, what the risks are. The information should be provided on the following areas:

·        the tissues donated and the intended clinical use of the donation, in general terms;

·        the need for testing for transmissible infections and the implications and follow-up of positive results;

·        information on how tissues are retrieved and stored;

·        the possible need for a review of medical records;

·        if applicable, the potential use of the tissue for research and development if it proves unsuitable for clinical use.

The duration of the consent must also be specified; this may be enduring (it remains in force unless it is specifically withdrawn) or time limited. The person giving consent may also withdraw it at any point before or after donation, providing that the tissue has not already been used, and it is important that they are informed of this right.

Consent should be taken only by those trained to do so. Seeking and obtaining consent is a sensitive issue; hence, staff seeking consent should have a good understanding of the activities they are seeking consent for. With the exception of anatomical examination or public display, where written consent is required, the Human Tissue Act does not specify the format in which consent should be recorded. Verbal consent documented either by audio recording or in the patient's notes is also valid.

Donor selection and testing

Tissue donors must be carefully selected to minimize the risk of transmitting diseases and to ensure suitable quality of grafts for transplantation. The major donor exclusion criteria described in the EU Directive is based on these two principles. The major reasons for deferral of donors include: malignancy, sepsis or significant local infection in the tissues to be donated, history or evidence of risk of transmissible viral infections such as HIV and hepatitis, risk of prion diseases and diseases of unknown aetiology [2]. Donors with a history of chronic or systemic autoimmune disease that could have a detrimental effect on the tissues to be donated must be excluded. In the case of deceased donors, the donors must be excluded where the cause of death is not known, although the post mortem report is likely to provide this information after tissue retrieval. Detailed donor selection guidance for living and deceased tissue donors for the UK Blood and Tissue Transplantation Services is available at http://www.transfusionguidelines.org.uk.

The donor selection process includes a structured interview with the living donors to obtain a detailed medical and behavioural history. In the case of deceased donors this interview is conducted with someone who knew the donor well – usually, but not always, a relative. The reliability of a family interview depends on how well the interviewee knew their deceased relative. Family members or even partners may be unaware of some aspects of the donor's medical history or may not wish to disclose certain information or they may be in denial about some risk behaviours such as intravenous drug use. Additional sources of information can supplement the process of donor selection. Information is sought from the general practitioner and, when necessary, from the referring hospital practitioner if the donor was admitted to hospital prior to death, to obtain as accurate a medical history as possible. The result of post mortem examination is reviewed, if one was carried out.

Donor blood samples for testing of the mandatory and any additional discretionary microbiological markers (determined by the donor's medical or travel history, e.g. malaria and Trypanosoma cruzi) must be obtained at the time of donation or within seven days postdonation for living donors. The sample from deceased donors must be obtained just prior to death or within 24 hours after death. Fluids administered in the 48 hours prior to death must be recorded to allow an estimation of any plasma dilution effect. Tissues from donors with plasma dilution of more than 50% can be accepted only if testing procedures used for screening are validated for such plasma dilution or if a pretransfusion sample is available.

The minimum requirement for mandatory tests required by the EU Directive includes screening for hepatitis C (anti-HCV), hepatitis B (HBsAg and anti-HBc), HIV (anti-HIV I and II) and syphilis. Individual nations are permitted to set higher standards than the minimum requirements. For example, anti-HTLV testing is mandatory in UK Blood Service guidelines whereas the EU Directive requires anti-HTLV testing only for donors living in or originating from high incidence areas or if the donor's sexual partner or donor's parents originate from high incidence areas. In the USA, HTLV testing is not required for tissues that are acellular. There is a requirement in the EU Directive to quarantine living tissue donations to obtain a second blood sample from the donor after an interval of 180 days to repeat the mandatory tests; however, if the blood sample taken at the time of donation is additionally tested by the nucleic acid amplification method (NAT) for HIV, HCV and HBV, a retesting is not required after 180 days. In UK blood services, all tissue donors are screened by NAT for HIV, hepatitis C and hepatitis B, in addition to the antibody and antigen tests mentioned above. The interval between the time of infection to the onset of detectable infection on screening tests is known as the ‘window period’. This window period for genome detection by NAT is much shorter than the window period for antibody detection. NAT thereby reduces the risk of transmission of infection during the early phase of the infection following exposure to the virus, before antibodies can be detected on screening. However, the serology screen may serve as an indicator of a past exposure and as an indicator of lifestyle risks. This combination of NAT and antibody test is especially important for testing of deceased tissue donors, where only a single blood sample can be taken at the time of donation. A negative NAT at the time of donation from a seronegative individual also removes the requirement for quarantining the donation from living donors, as explained above.

Tissue procurement

Tissue procurement or retrieval is a very different procedure for living and deceased donations. By necessity, living donations are retrieved during surgery by the operating team. Clear, written instructions, staff training and standard sterile kits are provided by the tissue bank for tissue collection. Regular auditing to ensure compliance with agreed procedures, detailed in a written agreement between the tissue bank and the hospital, is an integral part of a living donation programme. The critical aspect of retrieval is the identification of the donor, the donation and associated blood samples for donor testing and tissue samples for bacteriology and fungal testing. The use of barcoded donation number labels for donations, samples and associated documentation greatly increases the security in this step (see below).

With deceased donors, it is important to ensure the quality of the tissues removed. Tissues can deteriorate post mortem due to microbial contamination and autolysis, or be contaminated during the retrieval process. The optimal time and place to procure tissues from deceased donors is in an operating theatre, immediately after death or postcessation of circulation. However, the availability of these facilities for tissue donation is limited, and is generally restricted to tissue grafts that can be obtained during routine organ procurement procedures, such as removal of the heart for valve donation. In the UK, the large majority of tissue donations are performed in hospital mortuaries or on rare occasions in funeral homes. In addition, NHSBT Tissue Services (Liverpool) has a dedicated tissue donation facility, equipped with laminar air flow, for tissue retrieval; similar donation suites can be found both in Europe and in the USA. Consent is obtained from the donor family for moving the donor to the facility for tissue donation and returning the donor to the hospital or the funeral home within specified time limits. The environment is controlled to a defined specification, which is easier to maintain and monitor. The other advantages of an on-site dedicated facility are reduction in staff travelling time and the opportunity for close supervision and training of staff as senior expertise is available on-site.

Donor identification by means of a wristband, toe-tag or by mortuary staff is a crucial step before commencing the retrieval. A minimum of three points of identification such as name, date of birth, hospital number, address and tattoos (described by the family) are required to positively identify the donor. Before the tissue retrieval, a thorough external examination of the donor body appearance is conducted and recorded as a part of donor assessment. This examination should include detection and recording of tattoos, jaundice, evidence of drug use, body piercing, open wounds or signs of infection, scars and bruises, intravenous cannula sites, operation incision sites and other significant abnormalities.

Following death, autodegradation of all tissues commences as cells die and release lytic enzymes into the tissue. The intestinal microflora begins to migrate throughout the body, contaminating other tissues. The rate of both these processes is critically dependent on temperature; therefore it is crucial that warm ischaemia time is minimized and the body is refrigerated as soon as possible after death. In general, tissues should be recovered within the shortest possible period from the time of death. Standards vary around the world from 12 to 48 hours depending on the tissue and the processing method to which it will be subjected.

Minimizing bacterial contamination is further ensured by staff wearing sterile clothing and applying an aseptic technique during the tissue recovery process. This includes cleaning the donor using surgical detergents, alcohol wipes and sterile water; shaving the incision and skin retrieval areas; and draping the donor body before commencing the retrieval. Single-use equipment is used where possible.

Generally, skin grafts (if consented for) will be retrieved first to prevent the skin becoming contaminated by internal body fluids following incisions to remove internal tissues. In the UK, skin grafts are retrieved from the back of the torso and the back and front of both legs. Other tissue grafts are located internally and must be retrieved by incision. If retrieving heart, pericardium and thoracic aorta, the chest cavity must be exposed. Many other tissue grafts are obtained from the lower limbs, including bone (femur and proximal tibia), tendons and ligaments (Patellar, Achilles and hamstrings), meniscal cartilage and femoral arteries. An important aspect of tissue recovery is the careful reconstruction of the donor body. Extendable plastic or wooden prostheses are used to replace large bones.

Tissue processing

Tissue grafts are processed to improve safety, efficacy and for long-term storage of the donated material. There are multiple ways of processing, depending on the properties of the graft that need to be retained [3]. The core methodology by which viable tissues (skin, heart valve, cardiovascular and meniscus grafts) are processed comprises dissection, decontamination by antibiotic cocktail and cryopreservation. Whilst it may be desirable to sterilize a graft to increase safety, this is not practical where retention of donor cell viability is required. For many types of tissue allograft, in particular musculoskeletal allografts, the presence of viable cells is not required and, in these cases, processing reduces the risk of disease transmission by removal of blood and marrow and by reducing or eliminating contamination by chemical or physical means. Pooling of tissues from different donors during processing is not permitted by standards in Europe or the USA.

Each tissue bank should have a policy for acceptance or rejection of tissues if certain organisms are detected in bacterial screening during different stages of processing. The policy should be based on the pathogenicity of the organism and the validated effectiveness of any subsequent decontamination or sterilization steps.

Femoral heads from living donors removed during surgery in an operating theatre can be frozen and transplanted without further processing in the absence of bacterial or fungal contamination in validated tests.

Processing facilities

The required standard of EU tissue processing facilities is defined in Directive 2006/86/EC and is recognized as a key factor for the safety of tissues at risk of contamination. In general, the directive defines the minimum air quality in which tissues are exposed as Grade A (as defined in the European Guide to Good Manufacturing Practice, Annex 1) with a minimum background air quality of Grade D. The Directive defines a number of circumstances where lower standards must be justified and shown to give adequate protection to the tissue. Individual member states may apply more stringent criteria and may require a background of Grade B for some or all tissues exposed to the environment without terminal sterilization.

Supply and traceability of tissues

Directive 2006/86/EC requires the development of a European coding system, which will facilitate tracking of tissue from the donor to the recipient. A variety of different coding systems are currently in use, some using manually recorded codes and others using computerized systems with barcoding. The use of ISBT128 coding standard for blood is widespread in blood services in Europe and in the USA and has been further developed to include tissue product nomenclature (see www.iccbba.org).

Currently most tissue banks supply tissues direct to operating theatre departments and it is the responsibility of the receiving hospital to track from the receipt of the tissue to the graft's ultimate fate. Many tissue banks supply the hospital with a recipient record to be completed for each graft and returned to the bank. The users should always be advised:

·        to keep a log of tissue received and used;

·        to record any allograft unit numbers in the patient's notes;

·        to inform the tissue bank immediately of any adverse reaction that might be attributable to the tissue graft.

In many cases, tissues are supplied for specific cases and stocks are not held locally, but some units prefer to keep stocks of tissue immediately at hand for use in emergency or unexpected cases. Depending on the type of tissue, the hospital may require a licence to store tissue grafts for more than 48 hours; tissues containing donor cells such as cryopreserved skin grafts require a licence for storage, whereas acellular tissues, such as processed freeze dried bone grafts, do not.

Clinical applications

Tissue allografts are used in a variety of clinical indications in orthopaedic, spinal, cardiac, vascular, ophthalmic and plastic and reconstructive surgical procedures. Some of them are listed in Table 44.1.

Table 44.1 Indications for tissue allografts.

Types of graft

Surgical specialty

Surgical procedure (examples)

Heart valves

Cardiac

Valve replacement

Tendons and ligaments

Knee surgery

Ligament reconstruction

Meniscus

Knee surgery

Replacement of damaged meniscus (in selected cases)

Frozen femoral head, morcellized bone grafts

Orthopaedic (hip and knee)

Impaction grafting at revision joint surgery

Massive bone allograft

Orthopaedics

Post-trauma or tumour excision reconstruction

Demineralized bone

Spinal surgery, orthopaedic, oral and maxillofacial

Spinal fusion, nonunion or trauma defects, to fill cysts and tumour cavity defects

Cornea

Ophthalmology

Keratoconus, corneal ulcers, trauma, chemical burns

Skin

Burns

Burns, toxic epidermal necrolysis

Decellularized dermis

Plastic and reconstructive, breast surgery, abdominal surgery

Chronic wounds, breast reconstruction, abdominal wall repair

Blood vessels

Vascular

To replace infected prosthetic graft, lower limb ischaemia

Pericardium

Cardiac, andrology, ophthalmology

Vessel wall repair, Peyronie's disease, glaucoma surgery

Serious adverse events and reactions

Directive 2006/86/EC requires member states to have systems for reporting adverse reactions and events related to the procurement, processing, storage, testing or distribution of the tissue, which might seriously affect the recipient. The EUTCD definitions are as follows:

Adverse event:

Any untoward occurrence associated with the procurement, testing, processing, storage and distribution of tissues and cells that might lead to the transmission of communicable disease, to death or life-threatening, disabling or incapacitating conditions for patients or which might result in or prolong hospitalisation or morbidity.

Adverse reaction:

An unintended response, including a communicable disease in the donor or in the recipient associated with the procurement or human application of tissues and cells that is fatal, life-threatening, disabling, incapacitating or which results in or prolongs hospitalisation or morbidity.

In the UK, the HTA has developed an electronic reporting system for tissue and cell facilities, in line with the requirements of Directive 2006/86/EC. Each tissue bank receiving information about such a reaction or event must report it to the HTA when it comes to their attention and then again when the investigation of the event is completed. Such reactions and events can also be reported by the organization applying the graft, direct to the HTA.

Advances in tissue processing and regenerative medicine

There is still a need for traditionally banked human tissue, skin, bone, tendon, etc., but there is a recognition that, when grafted, these tissues may not provide the optimal environment for tissue regeneration; e.g. the presence of cells in the allograft (viable or dead) can give rise to an immune response and a delay or inhibition of recipient cellular infiltration or incorporation into the recipient. As such, traditionally processed and banked tissue essentially provides a replacement to damaged or diseased host tissue and some tissue, such as massive bone allografts, will never become fully incorporated into a recipient.

Regenerative medicine uses techniques of tissue engineering to remove donor cells without affecting the biological, biomechanical or biochemical parameters of the tissue [4]. Decellularized tissue, in particular decellularized dermis, has been available as an allograft since 1995 and several tissue banks now offer decellularized dermis and decellularized heart valves to surgeons. Clinical evaluation of results indicate that the decellularized tissue scaffold performs well, aids healing (if used in chronic wounds) and becomes infiltrated with recipient cells. Importantly, the infiltrating cells are not inflammatory cells resorbing the graft; instead they include progenitor and precursor cells, which can differentiate into an appropriate cell type, often influenced by factors remaining in the scaffold.

A major advantage of decellularized tissue becoming repopulated by recipient cells is that, over time, the grafted tissue becomes remodelled by the recipient cells, the donor extracellular matrix is replaced with recipient matrix and the allograft becomes part of the host. Two consequences of this are (1) a lack of the need for anti-inflammatory/antirejection drugs and (2) the ability of the grafted/remodelled tissue to grow and be able to repair itself as part of the recipient. Recent studies on implantation of decellularized heart valves indicate that the tissue does become repopulated with recipient cells and there is a reduction in complications and the need for further operations with time when compared to conventionally cryopreserved valves [5]. The use of decellularized heart valves opens up the possibility that when used in paediatric patients, only one heart valve transplant may be required during the lifetime of the patient and the implanted valve will increase in size when required as part of the recipient's natural growth.

The ability to add cells to banked tissue allografts is a major step forward in regenerative medicine treatment. Amniotic membrane has been used as a conventional allograft to treat severe ocular surface diseases for several years due to its ability to facilitate corneal re-epithelialization and reduce scarring and inflammation; however, more recently amniotic membrane has been used as a substrate on which epithelial stem cells can be expanded prior to transplant. The epithelial stem cells are derived from biopsies of the limbal region of the corneum; the stem cells can locate to stem cell niches when transplanted and thus provide a long-term solution to limbal stem cell deficiency. Limbal stem cells can be obtained either from the patient or from a donor.

Recent advances in regenerative medicine have involved adding recipient cells to a decellularized tissue, either in advance in the laboratory or at the point of transplant, making the procedure ‘personalised’ regenerative medicine. In 2008, a patient in Spain received a transplant of a portion of trachea that had been decellularized and then repopulated with her own cells, within a bioreactor [6]. Cells of different lineages, epithelial from bronchus and chondrocytes from bone marrow, were added to the inside and the outside of the trachea respectively at the University of Bristol (UK) before the repopulated tissue was shipped back to Spain. The cells were cultured in the bioreactor for four days before shipping. Similar procedures have been performed in the UK in 2010 using the entire trachea and adding stem cells 2–4 hours prior to transplant [7]. The initial transplant required 42 days for decellularization, but more recent transplants have been decellularized in 10 days or less.

Regenerative medicine may not always require human tissue for generation of a graft but it does require the addition of human cells. In 2006, it was reported that seven children/youths suffering from myelomeningocele and resultant dysfunctional bladder received successful transplants of artificial bladders impregnated with smooth muscle and bladder urothelial cells [8]. The bladders had been produced by erecting a scaffold and adding the cells in the laboratory. All patients reported improvement.

More recently, in June 2011, an entire artificial trachea was produced by scientists at University College London using a polymer-based nanocomposite and shipped to the Karolinska Institute in Sweden where recipient stem cells were added in a bioreactor for two days before being transplanted into a 36-year-old patient by the same surgeon who performed the first tissue-engineered tracheal transplant in 2008 [9].

Research is currently being performed on micronizing or solubilizing decellularized extracellular matrices such that the tissue is capable of being percutaneously injected to a site of required repair rather than incision. These matrices are biphasic in that they are a viscous fluid at low temperatures but set into a solid state at physiological temperature; therefore when injected into a repair site, the fluid becomes a solid tissue-like structure. These biphasic gels could be added with either bioactive factors or host cells to stimulate more rapid repair.

Regenerative medicine opens up the possibility of replacing almost every damaged or worn-out tissue with a new tissue capable of becoming part of the patient and returning normal functionality.

Summary

The banking of tissues is increasing within blood services, where expertise in donor selection, donor testing and quality management is being applied to the banking of many tissues including bone, tendons, heart valves and skin. Living donors can donate bone, amnion and heart valves during joint replacement, delivery of an infant or heart transplant surgery, respectively. All other types of tissue donation are made after death. For deceased donors, a thorough medical and behavioural history from a number of alternative sources is recorded to compensate for the lack of a face-to-face donor interview. This additional information should be sought from the donor's family doctor and the post mortem examination report (where applicable).

Living donations are retrieved during surgery by the operating team. In the UK, the large majority of tissue donations after death are performed in hospital mortuaries. Tissues should be retrieved within the shortest possible time period after death. Delayed tissue recovery increases the risk of bacterial contamination. Minimizing bacterial cross-contamination is ensured by applying aseptic retrieval techniques.

Tissue processing is necessarily open and usually involves decontamination or terminal sterilization. As a minimum, facilities for tissue processing in the EU should be designed to achieve class C for tissues destined for terminal sterilization and class A, with class D background, for the manipulation of tissues in the absence of a terminal sterilization step, but following chemical or antibiotic decontamination. Many EU member states apply more stringent requirements.

Traceability is an essential aspect of the quality chain and should be supported by machine readable identification codes. If these are compatible with blood coding systems, traceability within the transplanting hospital can be greatly enhanced. Requirements are now in place for the reporting of serious adverse events and reactions to regulatory authorities to support the further enhancement of safety and quality in tissue banking.

Tissue banking and processing is a rapidly evolving field and is becoming more and more related to personalized regenerative medicine. Conventional tissue allografts often require replacement (with another allograft) with time, but tissue engineered allografts raise the possibility that, particularly in children, only one allograft will be required for the lifetime of the patient.

Key points

1. Tissue grafts are used in surgical procedures to replace damaged or lost tissues in patients. Most tissue allografts are donated by deceased donors and some by living donors undergoing surgery.

2. The European Union Tissue and Cells Directives (EUTCD) set out to establish a harmonized approach to the regulation of tissues and cells across Europe, requiring EC member states to have inspection and accreditation systems to ensure that all tissue banks comply with mandated technical requirements.

3. Consent should be taken only by those trained to do so and the associated discussion should include information on intended clinical use of the tissue, including research use, virological testing and the implications of positive results.

4. The primary source of donor selection information for deceased donors is the interview with someone who knew the donor well and this may not necessarily be the person who gives consent for the donation. Where a post mortem examination has been performed or is scheduled, the results should be reviewed as part of the donor selection process.

5. An external examination of the donor body should be conducted, recorded and form part of the donor selection assessment prior to the tissue recovery. After tissue recovery, it is important to carefully reconstruct the donor body. Aseptic procedures must be followed to minimize bacterial contamination.

6. Processing tissue reduces the risk of disease transmission by removing blood and marrow and by reducing or eliminating contamination by chemical and physical means. Pooling of donations during processing is not permitted by standards in Europe or the USA.

7. Tissue allografts have been used in surgical procedures for many years with great success but with known limitations. Regenerative medicine using decellularized and tissue engineered allografts may allow full incorporation of the graft into the patient such that it becomes part of the patient and is able to grow with and repair itself.

References

1. Schulz-Baldes A, Biller-Andorno N & Capron AM. International perspectives on the ethics and regulation of human cell and tissue transplantation. Bull World Health Org 2007; 85: 941–948.

2. Chandrasekar A, Warwick RM & Clarkson A. Exclusion of deceased donors post-procurement of tissues. Cell Tissue Bank 2011; 12: 191–198.

3. Galea E (ed.). Essentials of Tissue Banking, 1st edn. Springer; 2010, 245 pp.

4. Mirsadraee S, Wilcox H, Korossis S et al. Development and characterisation of an acellular human pericardial matrix for tissue engineering. Tissue Engng 2006; 12: 763–773.

5. da Costa FD, Santos LR, Collatusso C et al. Thirteen years' experience of the Ross operation. J Heart Valve Dis 2009; 18: 84–94.

6. Macchiarini P, Jungebluth P, Go T et al. Clinical transplantation of a tissue-engineered airway. Lancet 2008; 372: 2023–2030.

7. Baiguera S, Birchall MA & Macchiarini P. Tissue engineered tracheal transplantation. Transplantation 2010; 89: 485–491.

8. Atala A, Bauer SB, Soker S et al. Tissue engineered autologous bladder for patients needing cystoplasty. Lancet 2006; 367: 1241–1246.

9. Jungebluth P, Alici E, Baiguera S et al. Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet 2011; 378: 1997–2004.

Further reading

Barron DJ, Khan NE, Jones TJ, Willets RG & Brawn WJ. What tissue bankers should know about the use of allograft heart valves. Cell Tissue Bank 2010; 11: 47– 55.

Eagle MJ, Rooney P, Lomas R & Kearney JN. Validation of radiation dose received by frozen unprocessed and processed bone during terminal sterilisation. Cell Tissue Bank 2005; 6: 221–230.

Fehily S, Warwick RM, Kearney J & Galea G. Bone banking in the UK blood services. Organs and Tissues 2004; 3: 177–182.

Getgood A & Bollen S. What tissue bankers should know about the use of allograft tendons and cartilage in orthopaedics. Cell Tissue Bank 2010; 11: 87– 97.

Kearney JN. Guidelines on processing and clinical use of skin allografts. Clinics in Dermatology 2005; 23: 357– 364.

McDermott ID. What tissue bankers should know about the use of allograft meniscus in orthopaedics. Cell Tissue Bank 2010; 11: 75–85.