BURN CARE AND PREVENTION JOURNAL

Tissue banks are a relatively new concept in the emerging world. This review aims to comprehensively analyze the challenges and solutions for establishing tissue banks in developing nations. The burden of burns and road traffic accidents in the developing nations is disproportionately higher than in developed countries and so are the mortality rates associated with them. There is an unmet need for more tissue banks to counteract these problems. This was obvious from the historical aspect, with the era of tissue transplant emerging 3 decades later in developing nations versus developed nations and with many regions that have still not yet initiated tissue transplantation. The challenges ahead involve a lack of infrastructure, a lack of awareness, and many legal and ethical issues. A multidisciplinary team effort, even despite a lack of resources, is the mainstay of progress in tissue banks in resource-limited regions. The potential solutions to overcome this problem include simplified and applicable legislations, the development of continuous and long-term awareness programs, and integrated and harmonious efforts from all regions of the world. We hope that this review will help transplant authorities throughout the world to understand this problem statement and the need for timely action for concerting the path to successful tissue banking in emerging nations.

KEY WORDS: Burns, Legislations, Skin allograft, Skin bank, Tissue procurement, Tissue transplantation

In developing nations, the processes of organ and tissue transplantation are still evolving compared with in developed countries, with considerable deficits in deceased donations in most of the developing world.^1,2 In the context of tissue transplantation, the lag is even worse. This has remained a neglected field of transplantation. In actuality, tissue transplantation is an old concept in the medical field, which has boomed in recent years. Tissue transplantation involves donation of tissues such as skin, amnions, blood vessels, heart valves, and bones and transplanting them to a debilitated recipient. Herculean efforts have been made to establish tissue banks because banks remain a cornerstone for conducting systematic tissue transplants. As per the American Association of Tissue Banks (AATB),³ a tissue bank is defined as "An entity that provides or engages in one or more services involving tissue from living or deceased persons for transplantation purposes. These services include obtaining authorization and/or informed consent, assessing donor eligibility, recovery, collection, acquisition, processing, storage, labelling, distribution and dispensing of tissue."

The simplicity of tissue transplantation lies in the fact that, unlike organ transplants, where few recipients benefit, in tissue transplants, a single tissue transplant donor can benefit a large number of recipients. Likewise, the burden of lifelong immunosuppression in organ transplant is not a necessary aspect in tissue transplant, as tissues are not that immunogenic, and also there is extensive processing of tissues before transplant. It comes as no astonishment then that establishing tissue banks will improve the quality of lives of many ailing patients and even save lives in patients with large whole thickness burns. This is a growing matter of concern in that tissue transplantation still lags in many emerging nations, with the problem seeming to encompass a lack of knowledge, infrastructure, legislation, and implementation.

HISTORICAL PERSPECTIVE OF TISSUE BANKING

Tissue transplant may appear to be a new field, but it is an old entity that has recently flourished. From a historical perspective,^4,5 in 1871, George Pollock utilized his skin graft in a burn case, and, in 1881, Girdner was the first to use a deceased donor allograft in a burn patient. In 1881, William Macewen was the first orthopedic surgeon to transplant an allograft from a rachitic child to humeral shaft reconstruction. In 1869, skin grafting was first described by Reverdin. In 1903, Wentscher demonstrated that skin grafts can be stored and refrigerated for later use. In 1908, Erich Lexer started using bone allografts from amputees for reconstruction surgeries in bone tumors and osteomyelitis. In 1910, Bauer first reported refrigeration of bone allograft with successful transplants. In 1911, Tuffier used thin refrigerated bone slices for transplantation. In 1947, Bush and Wilson were among the first to build a bone bank. In 1948 and in 1952, respectively, Baxter and Medawar were the early companies to broaden tissue research involving storage and preservation techniques. In 1949, George Hyatt established the first tissue bank in the United States. In 1952, Rudolph Klen started a tissue bank in Czechoslovakia. In 1955, the first tissue bank in the United Kingdom was formed in Leeds. Other European countries followed in the footsteps of the United Kingdom; in Germany, the first tissue bank was started in Berlin and in 1963 Poland inaugurated its first tissue bank.

The advent of tissue banking in developing nations began nearly 3 decades after the developed world. In 1981, Burma was the first nation among Asian countries to establish a tissue bank; the bank was established in Rangoon under a program supported by the International Atomic Energy Agency (IAEA). In 1984, Thailand acquired its first tissue bank at the Bangkok Biomedical Center. In both Myanmar and Thailand, there are no specific laws for tissue donation. In 1988, The China Institute for Radiation Protection Tissue Bank was established in Shanxi Province of China. In 2000, the tissue bank of China obtained an influential upgrade and became known as the OsteoRad Biomaterial Co. Ltd. In 1988, India established its first tissue bank (the Tata Memorial Hospital Tissue Bank in Mumbai) under the IAEA. In India, an organ act was established in 1994 as the Transplantation of Human Organs Act, which was amended in 2000 as the Transplantation of Human Organs and Tissue Act; this Act laid out norms for skin and tissue banks in India. In 1988, Singapore received its first bone bank, the National University of Singapore Bone Bank, which also became a training center and is a major success in tissue banking in the Asia Pacific region. In 1988, the first tissue bank in Indonesia, known as BATAN, was established in Jakarta. Most nations in the developing world have opt-in informed consent and preliminary staged deceased donor programs, hence contributing further to the hurdles of broadening the initial work of tissue banking. In 1990, Hong Kong developed its first tissue bank. In 1993, the Hanoi tissue bank was formed in Vietnam, which has separate laws for organ and tissue transplants. In 1996, a tissue bank was established in Sri Lanka with collaboration from the IAEA. Overall, there are only a few centers in developing nations, with many nations yet to start tissue bank centers.

THE URGENCY FOR TISSUE BANKS IN DEVELOPING NATIONS

The bulk of the ongoing need for allografts comes from burn injuries. As per the World Health Organization, an estimated 180 000 deaths every year are caused by burns, and these are one of the leading causes of disability-adjusted life years in the emerging world.⁶ Among emerging nations, India leads in the number of burn cases, with around 1 million cases every year and most cases requiring an allograft.⁷ Children with burns from developing nations have 2 times higher chance of mortality and 20 times higher chance of hospitalization compared with children with burns in the developed world.⁶ The skin allograft can be lifesaving in these scenarios.

Previous studies have shown that early skin grafting in cases of life-threatening burns like full-thickness burns can significantly improve mortality.^8-10 The skin graft can also be used in conditions like nonhealing ulcers, pressure sores, other exfoliating skin disorders, and for cosmetic purposes. Another relevant area where skin and bone transplants are required is polytrauma. The World Health Organization reported that approximately 1.35 million people die every year as a result of road traffic crashes. Almost 93% of the world’s fatalities on the roads occur in low- and middle-income countries.¹¹ The statistics easily depict the gap between need and supply of skin and tissues in the developing world.

POTENTIAL IMPACT OF TISSUE BANKS IN THE MANAGEMENT OF BURNS IN DEVELOPING NATIONS

Because of the unmet need of allograft availability and burden of burn wounds,⁶ developing a tissue bank that serves burn patients is a top priority. Skin grafting is now the standard of care for all burn centers across the world.¹² Allografts can accomplish the job of wound dressing in cases of small burns; however, in larger burns, allografts are lifesaving. Allograft skin is the best and least expensive substitute compared with artificial skin substitutes in this part of the world; therefore, there should be mandated attempts to expand deceased donation programs in the developing world. There also remains enthusiasm in modifying tissues for better suitability, cost-effectiveness, and outcomes from the very beginning. The development of “AlloDerm” was one such innovation that intended to provide a nonimmunogenic way to overcome problems with skin allograft availability.^13,14 Fetal skin has also been used as an allograft with fascinating results in pediatric burns.¹⁵ Apart from skin, another high-utility tissue is amnion, which has been used for burns for over a century^16-18 owing to its inherent property of being a reservoir for growth factor and cytokines, with minimal immunogenicity. In low-economy nations, amnion, because it is cost-effective, is used as a temporary dressing in burns. Chemicals like silver nitrate in amniotic membranes have been used with great success as a biological dressing for moderate to severe burns.¹⁹ Preservation methods like glycerol have been used where amnion can be stored for extended periods.²⁰ The glycerol preservation technique is an attractive option compared with the cryopreservation technique, mainly due to financial reasons.²¹

CHALLENGES IN THE DEVELOPMENT OF TISSUE BANKS AND POTENTIAL SOLUTIONS

Filling the knowledge gap
Lack of awareness remains in developing nations on organ and tissue transplants,²² which are not just limited to a lack of awareness in the general population. Some qualified health professionals still have little knowledge about the legislation and procedures of tissue banking.²³ To ensure progress in tissue transplantation, regular mass campaigns on organ donations involving tissue donations should be done. Awareness programs should also include medical and paramedical professionals from every level. The Nepal model,²⁴ which is a long-term awareness program in tissue banking, is an excellent approach that can be followed by others. In the medical school curriculum, clear and concise chapters involving organ and tissue transplants should be upgraded, as it will boost knowledge among medical students, thus greatly affecting the cause. Combating false myths, social taboos, and false religious beliefs involved in deceased donation are daunting tasks in some regions of the world.^25-27 In Iran,²⁸ professional transplant counselors have improved organ donation rates; similarly, initiatives are needed in other regions to increase tissue transplant rates. Cultural beliefs in some parts of the world that the unmutilated body should be buried are difficult to change. It is unarguably correct that boosting knowledge and influencing changes in attitudes and practices for skin tissue transplant can increase the overall human development index.

Simplicity in legislations of tissue transplant acts
In developed nations like Australia and Europe, opt-in and opt-out consent practices exist, and these practices have partly contributed to the success of organ and tissue transplants.²⁹ As shown recently, the Spain model of transplant remains at the top with regard to donation efforts,^30,31 and the concept of presumed donation or opt-in donation is a major reason for this success. In many developing nations like India, individual informed consent is mandatory before donation; therefore, in these regions of the world, knowledge among the population on tissue donation is a key factor for the establishment of new tissue banks. Similarly, an altruistic donation is common in developed nations, which is not allowed in many legislations in emerging nations, to avoid exploitation of the weak and to avoid organ trafficking.

Although changes to organ transplant practices in developing nations has made rather slow progress, changes in aspects of withdrawal of life support treatment, brain dead declaration, and donation after cardiac death have helped to successfully expand transplant programs. One major problem is the applicability and implementation of tissue rules. For example, in many countries, brain death declaration and reporting may be mandatory in all cases; however, actual reporting and conversion rates of brain dead to brain dead donor remain astonishingly low.

State and national legislative bodies continue to take further steps to formulate rules that are better suited for organ and tissue transplant. A recent example comes from Kerala, a state in the Indian subcontinent, where the state government passed a landmark decision that gave authority to concerning physicians to withdraw and end support in cases of brain death.³²

Unresolved issues in ethics
Donating an organ or tissue is considered a gift for humanity and is a selfless act. There are some obvious issues with tissue transplants, especially with regard to monetary aspects. Unlike an organ transplant, where the organ is transplanted quickly so as to maintain its vitality, with tissue transplant, the graft needs to be processed and preserved in many ways, and sometimes it may take years before it is used. Here, the cost involved is taken up by nonprofit or profit organizations, with commercialization unavoidable. All forms of organ and tissue acts condemn any form of financial profiting during the transplant process,³³ but financial neutrality can be easily broken in tissue transplants. The only way to combat this aspect will be a regulated and centralized authority for all forms of tissue processing and distribution. Families of donors never get any financial incentives after donation,³⁴ and this matter is still subject to debate, especially in developing countries, where on the one hand it can promote donation and on the other can create a loophole for commercial profiting.

Contrary to organ transplants, where a recipient’s death is halted from the donation, in tissue donation, only the crippling condition of the recipient improves. Thus, convincing a family to donate tissue can be relatively difficult, especially for skin grafts, which in addition to use for extensive burns are also used for cosmetic purposes. In the bulk of transplant centers, retrieval of different organs and tissues is done by different teams, thus, understandably, further lengthening the psycho-social trauma of the family of donors, with the end result sometimes being an unwillingness for further donation. An integrated approach of retrieval of all organs will help to solve this matter, although resource limitations can slow the process.

Safety of grafts
In developing nations, infectious complications remain cumbersome and complicate all aspects of skin banking.^35,36 There is no fixed series of investigations that should be applied to screen donors, as various geographic regions can have diverse infectious culprits. Hence, blood investigations should vary according to the location and clinical suspicion. An excellent example comes from the screening of human T-cell lymphotropic virus type 1 under AATB³ in the United States and screening of parvovirus B19 in Japan,³⁷ which are considered contraindications for transplant if positive. In some parts of the world, these organisms are not even tested because of the extremely low endemicity. In general, donors should be negative for organisms like hepatitis C virus, hepatitis B virus, human immunodeficiency virus, and syphilis. It is a matter of deliberation whether other organisms like cytomegalovirus should be regularly screened in deceased donors. There is also an important concern of donors with regard to the incubation period after infection; hence, the possibility and possible consequences to recipients should be disclosed beforehand to avoid medical chaos after transplant. There are endemic regions where parasites like dengue and Zika are common; hence, a travel history is important to rule out any chances of disease transmission. The decision to test for any organism should be based on history and physical examination and should measure all aspects of benefit and risk to the recipient.³⁸

Because SARS-CoV-2 has affected all aspects of health care facilities, organ and tissue transplant centers are not an exception. As of now, there is limited information on the effects of physical and chemical tissue processing methods on SARS-CoV-2 neutralization; therefore, stringent measures are needed in screening of donors to avoid possible transmission in tissue transplants.³⁹

Another aspect is microbiological contamination during transport, storage, and processing techniques. Stringent sterilization measures with a regular quality check should be obligatory. Even after transplant, most recipients have infectious complications, and, for this, antibiotic stewardship program and infectious disease specialist departments should be strengthened. Because there are different laboratory methods with different accuracies for testing viability of tissues before transplant,⁴⁰ a harmonized and universal standard of measurement should be made.

Necessity of proper registry with integrated efforts
Role models for advancement of tissue banks include developed nations like the United States, Canada, Australia, and Japan. In the developed world, a general body has managed the liability for initiating tissue banking and for paving its further progress. In the United States, tissue banks are governed by the National Organ Transplant Act, and AATB³ is a transplant organization that has accredited more than 100 tissue banks and is a role model for the development of tissue banking in other nations. In Canada,⁴¹ the Biologics and Genetic Therapies Directorate, Health Products and Food Branch of Health Canada, and the Canadian Standards Association jointly regulate different aspects of cell and tissue banking and transplantation. In Australia,⁴² under the Therapeutic Goods Act, tissue banking was expanded. The European Association of Tissue Banks⁴³ has paved the path for organizing tissue banking in many European regions. The Asia Pacific region cadres the greatest number of emerging nations; so far, there were no clear and simplified consensus or guidelines for tissue banking, although the Asia Pacific Burn Association⁴⁴ has recently provided guidelines that follow recommendations from other successful nations. However, the universal applicability and implementation in various regions will still take more time and effort. In emerging nations, tissue banks face many challenges in terms of infrastructure for tissue retrieval, storage, processing, and preservation techniques.

Another important difference is that a nation-wide registry like the Organ Procurement and Networking Team in the United States has helped to further increase tissue donation rates. Proper nation-wide registry formation in developing countries, coordinating and regulating all aspects of tissue and organ transplant, from the root level of intensivists, surgeons, retrieval centers, to transplant centers, and tissue banks are of utmost relevance to overcome the financial constraints and ensure quality progress in tissue banking.

In India, the rate of deceased donor transplant was augmented in southern states by the efforts of a nongovernment organization called the MOHAN Foundation.⁴⁵ This organization has provided pioneer work in expanding the donor pool. Similarly, a governmental or nongovernmental body carrying the responsibilities of the smooth functioning of tissue transplants can do a great job. This will also ensure a transparent system not only for tissue allocation but also for tissue distribution.

Internal audits conducted monthly and external audits done yearly among individual transplant centers and notifying their findings to a central body can further help in the development of tissue banking programs. The quality check should be a continuous process, as it will further increase the chances of improvement. Centers with expertise should cooperate and guide others in the foundation of tissue banks in their respective regions. An exemplary example is the TATA Memorial Tissue Bank, which has considerably contributed to the development of other tissue banks in India. Similarly, BATAN in Indonesia cooperated in establishing the second tissue bank in Indonesia.

Tissue banking needs a multidisciplinary approach, requiring assistance from medical teams, counselors, laboratory personnel, and experts in storage and processing of tissues. Tissue banks also require highly specialized equipment for processing, like ionizing radiations, and also preservation techniques. Resource-restricted nations often lack staff and equipment; however, compartmentalization of available resources can yield inspiring results, as shown with the TATA Memorial model of Mumbai in India.^46,47 Instead of giving authority to a specialized individual for tissue retrieval, in the initial stages of tissue banking, any health care personnel with appropriate training in process should be appointed. Moreover, the authorization process for starting tissue banks should be staged and lenient. Compared with other tissues, skin bank establishment is relatively easy versus establishment of other banks.

Skin and other tissue banks in developing countries have a long road ahead of them. Flexible and stepwise approaches in the establishment of tissue banks are required. The primary need is to ensure that high-quality and safe allografts are given to the neediest of all individuals and that all feasible attempts are made to reach the minimum standard of care. The developing world has its own set of challenges, from infrastructure to legislation to lack of awareness. During the process of expansion, regulatory bodies must formulate the needed tissue transplant guidelines to monitor for organ trafficking in any form. The basic guidelines involved in skin and other tissue transplants should be common to all emerging nations, with modifications per cultural and regional differences, as this will ensure perpetual progress in tissue banking development. Lastly, a united and harmonized effort of all nations can hasten the progress of tissue transplant in the developing world.

Volume: 1 Issue: 1 March 2021

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