John Hunter (1728–1793), British Surgeon and Physician who contributed much to medicine. His work on bone physiology was monumental and ahead of his time.
(Reference: Ottley D. The Life of John Hunter, FRS Haswell, Barrington and Haswell. 1839, Philadelphia.)
The history of bone transplantation starts with a chicken. The first successful bone grafting on record was performed by John Hunter (1728–1793) who transplanted a spur of a hen into the leg of a cock. Extraordinary additions to the knowledge of bone transplantation and bone growth were made by this individual.* Despite technical limitations, compared to today, Hunter carried out some of the most significant experiments with bone that stand unique to the present. It would not be an exaggeration to say that never has a single man devoted as much energy and time to the study of bone as did John Hunter. His observations on the effects of castration on the growth of deer antlers laid the foundation to the study of the effect of endocrine secretions on bone.
At Hunter's time the prevailing doctrine of bone growth stated it took place by interstitial accretion. Hunter put this idea to test by implanting two shots 2 inches apart in the tibias of pigs and fowls. He discovered in his studies of sacrificed animals that the shots remained the same distance apart, but were much further from the ends of the tibia, thus proving the bones grew in length. Knowing the discovery that madder (a red dye obtained from the roots of Rubia tinctorum) is deposited in the bones, Hunter periodically fed young pigs madder and was thus able to prove that bones also grow in thickness by the addition of the new layers of bone on the outer surface as the inner layers, next to the bone marrow cavity, are resorbed.
Since Hunter's fundamental discoveries on bone growth, many scientists have contributed to the knowledge of bone growth, healing and grafting. These have led to the acceptance of bone transplantation as a clinical entity and the development of tissue banking, which allowed the development of the transplantation of allogeneic bone on a large scale.
It has been disappointing to see the gospel of bone transplantation and tissue banking preached by Hyatt, Kreutz and the present authors to be subverted to pecuniary interests propagated by commercial advertisement. The latter has been frequently based neither on documented clinical results nor on applicable laboratory studies. We have struggled to write with detachment and concentrate on the well-established facts and findings.
In 1865, NA Pirogoff, who, among other things, pioneered the use of plaster casts, noted that bone regeneration and repair were not entirely understood (Voloshin and Bernini (1998). Although much progress in the study of bone physiology and repair have been made since John Hunter's time, Pirogoff's statement of some 150 years ago still holds true, at least partially.
If a missing segment of bone cannot regenerate itself, but if closely approximated bone ends can unite, then why not replace the missing segments with other bones and have these heal to the ends of the host bone? The accounts of replacing injured and diseased bones and joints are provided by Ollier (1867), Lexer (1925), Küttner (1911) and others. In the 6th and 7th decades of the past century Ottolenghi (1966), Parrish (1973), Zatzepin (1984), Mankin et al (1983) and Mnaymneh et al (1983) have performed transplantation of massive bone allografts. However, the earliest and persistent efforts in bone transplantation can be justifiably attributed to Albee, although he worked mainly with autografts (Albee 1923).
The modern era of bone allograft transplantation has been ushered in large measure by the development of tissue banks through which bone allografts became readily available (Malinin 1976; Kreutz 1951). Initial experience with transplantation of large bone allografts was gained from tumor surgery (Mnaymneh et al 1985). Later, encouraged by the results with reconstructions of the extremities following resection of tumors, massive allografts started being used with regularity for non-tumorous conditions, particularly for the revision of failed hip arthroplasties.
As with all surgical procedures, the more operations are performed and the longer the patients are observed, the more complications are recorded. Some of these include infections. Some can be attributed to technical errors, the correction of which resulted in the reduction of complications. However, some complications, such as late fractures of large grafts are inherent and are undoubtedly related either to the allografts themselves or to the interactions between the allograft and the host. To this end, it is important to be fully aware of what happens to transplanted bone.
A large body of information has been collected on bone, cartilage and tissue transplantation through experimental studies, although not all of it might be applicable to man. Despite this limitation, the success of clinical transplantation depends on the biological behavior of musculoskeletal allografts and the host-graft interactions. Therefore, it is worthwhile to apply information gathered on animals in the laboratory to humans, but this must be done with caution.
Because of the relative paucity of information on the long-term behavior of bone allografts initially transplanted into humans, the development of methods for bone allograft preparation proceeded largely along empirical lines. Virtually everything was tried. Bone allografts were boiled, steam autoclaved, immersed in mercurial solutions, washed with a garden hose in the yard then sterilized with ethylene oxide, immersed in beta-propiolactone, extracted with ether, methanol and chloroform, irradiated and sterilized by repeated freeze-thawing, to name but a few. On the other hand, bone allografts were likewise excised under aseptic conditions and preserved by freezing or freeze-drying. For clinical transplantation, aseptically excised frozen or freeze-dried allografts have over the years emerged as the allografts of choice. The immunogenicity of these grafts is reduced, more so in freeze-dried allografts than frozen ones, as compared to fresh bone allografts. The reason for this is most likely the destruction of the antigen presenting cells that reside in the bone marrow. Because of the general acceptance of the allografts prepared by these methods, in this book, we will deal primarily with allografts which were either freeze-dried, rapidly frozen, or frozen at a controlled cooling velocity after exposure to cryoprotective agents. In addition, because of the magnitude of the subject and the need to focus on specific aspects of musculoskeletal tissue transplantation, the results as well as the techniques of clinical transplantation will be emphasized.
Bone grafting arose from clinical need more than 100 years ago. Paradoxically, the practice led to the science. This is largely still the case, but the field has expanded so rapidly that it is difficult to synthesize all findings. The purpose of this book is to bring together information on bone grafting, cartilage and soft tissue transplantation as well as tissue banking in a systematic and comprehensive manner. This has been aided by the authors’ long-standing endeavors in tissue banking and musculoskeletal transplantation. It is hoped that the information presented herein will aid the surgeon in the treatment of disorders and diseases of bone and other musculoskeletal structures.
The publication of this book follows two important events in bone physiology. First, the isolation and encoding of several bone growth proteins named bone morphogenetic proteins, BMP 1–7. These are members of a large family of growth and differentiation factors (TGF-B). Second, the synthesis of bone growth factors by genetic engineering that stimulates osteogenesis. The function of the latter, however, is still under scrutiny. In addition, the work with pluripotent stem cells has captured the imagination of scientists and clinicians concerned with bone regeneration. These efforts, in turn, resulted in a new field, tissue engineering. Various technologies described in this field may well have a lasting impact on the treatment of musculoskeletal diseases in the future, but so far their impact has been limited.
Any new developments in medicine have a potential to become controversial. Stem cell research and therapy are no exception. However, it can be hoped the imagination and skill of new researchers will result in a new means of treating patients with diseases of the skeletal system. At present, cell therapies and tissue banking share common ground as banked bone and other tissues can provide scaffolding and matrix for growth of new tissues from cells. Thus, even with the anticipation of the new developments, tissue banking will retain its place in regenerative medicine.
Bone grafting and tissue transplantation is performed by several surgical specialties. Orthopedic surgeons have always pioneered bone grafting. However, plastic surgeons, neurologic surgeons, otolaryngologists, oral and maxillofacial surgeons and dentists have also performed musculoskeletal tissue transplantation. Since allogeneic bone transplantation is performed by many specialties, members of these specialties should be adept in excising bone grafts and knowledgeable of bone allograft biology. This knowledge will be helpful in assessing the final outcomes.
The repair of musculoskeletal tissues and bone healing are of vital concern to all surgeons. While the majority of surgical techniques now practiced are based on methods developed long ago, the techniques cumulatively referred to as “tissue engineering” have lately made their appearance. The subject is still controversial, as is usually the advent of any new therapeutic modality. Although it can be believed the developments in this field may result in significant advances, in practice these still have not materialized to a significant degree. Therefore, it seems too early to abandon conventional methods of musculoskeletal tissue transplantation and tissue banking, subjects to which this book is dedicated.
Despite numerous publications on bone transplantation and bone banking, few books combining the topics have appeared. The present book deals with both topics in a historical perspective.
The history of bone transplantation, autologous and allogeneic, is long and complicated, but one could not expect something simple in an endeavor that spans over 100 years. Bone transplantation elicited many controversies resulting both from laboratory investigation and surgical practice. Some of these have not been resolved. Research on skeletal grafting did not proceed at a uniform rate. Instead, periods of intense activity were intermittent with periods of relative dormancy. In the last decade, research on skeletal grafting has once again gathered momentum.
Organized tissue banking is of a more recent vintage. The US Navy Tissue Bank and several scientists and clinicians who gained experience in this institution provided the impetus for its development. The Office of Naval Research had also a long period of supporting endeavors in musculoskeletal transplantation and tissue preservation.
The University of Miami Tissue Bank was established in 1970 to fill the void left by the US Navy Tissue Bank when it successfully completed the demonstration of practicality of tissue banking and discontinued supplying civilian surgeons with tissue allografts. The experience of over 40 years gained by the authors in this institution allowed for the gathering and organizing of the material on which this book is based. Gathering and going over the accumulated data and experience has reinforced our feeling that long-term success with musculoskeletal tissue transplantation warrants not only an incentive for further investigation, but also for continued use of these allografts in reconstruction of the skeletal system.
- Albee FH. A Surgeon's Fight to Rebuild Men. EP Dutton & Co, Inc. New York, 1923.
- Kreutz FP, Hyatt GW, Turner TC, Bassett AL. The preservation and clinical use of freeze-dried bone. J Bone & Joint Surg (Am), 1951;33:836–72.
- Küttner H. Einige Dauerresultete der Transplantation aus der Leiche und aus der Affe. Verhandlungen Deutsche Gesselschaft für Chirurgie, 1913;11:353–65.
- Lexer, Erich. Joint transplantation and arthroplasty. Surg. Gyn. & Obst., 1925;40:782.
- Malinin TI. University of Miami Tissue Bank: Collection of postmortem tissues for clinical use and laboratory investigation. Transpl Proc, 1976; 8 (Suppl 1): 53–58.
- Mankin HJ, Doppelt S, Tomford WW. Clinical experience with allograft transplantation: The first ten years. Clinical Orthopaedics and Related Research, 1983;174:69–86.
- Mnaymneh W, Malinin TI, Makley JT, Dick HM. Massive osteoarticular allografts in the reconstruction of extremities following resection of tumors not requiring chemotherapy and radiation. Clin Orthopaedics & Related Research, 1985;187:76–87.
- Ollier L. Traite Experimental et Clinique de la Regeneration des os et de la Production Artificielle du Tissu Osseux, Victor Masson et Fils, Paris, 1867.
- Ottolenghi CE. Massive osteoarticular bone grafts.Transplantation of the whole femur. J Bone & Joint Surg (Br), 1966;48:646–59.
- Parrish FF. Allograft replacement of all or part of the end of a long bone following excision of a tumor. J Bone & Joint Surg (Am), 1973;55:1–22.
- Voloshin I, Berninin PM. Nikolay Ivanovich Pirogoff: Innovative scientist and clinician. Spine, 1998;23: 2143–46.
- Zatzepin ST. Limb sparing operations in bone tumors. Medizina, Moscow, 1984.