Yu Xiaodong
Department of Orthopedics, Changsha Hospital of Traditional Chinese Medicine (Changsha Eighth Hospital), Changsha 410100, Hunan Province
【Abstract】This paper mainly studies xenotransplantation and describes the research progress of this scientific research topic
【Keywords】xenogeneous bone ; Graft; Study; investigate
Bone grafting is a commonly used treatment for nonunion and bone defects caused by trauma, tumors, etc. Since 1668, when VanMeekren performed the first bone graft, bone grafting has been the most common tissue transplant in humans. According to the material of bone grafting, it can be divided into autologous bone grafting, allogeneic bone grafting and xenogeneic bone grafting, as well as tissue engineering artificial bone grafting carried out in recent years. With the deepening of the treatment methods, bone induction experiments and clinical research, the research on xenogeneic bone grafting, especially composite xenotransplantation, has made great progress. The purpose of this article is to review the research status and progress of immunogenicity and immune response of xenogeneic bone, preparation of xenogeneic bone, bone induction of xenogeneic bone, and composite xenotransplantation.
1 Immunogenicity of xenogeneic bone and transplant immune response
Xenogeneic bone has a well-defined immunogenicity. Its immunogen is mainly found in the organic matter of bone, and the minerals in bone are not antigenic. Liu Weisi et al. found for the first time that cortical bone antigenicity was mainly located on bone cells and Harvard's endothelium, while bone matrix did not show obvious antigenicity. Luo Zhuojing et al. found a similar situation to the distribution of cortical bone antigen through the study of cancellous bone antigenicity, which was negative staining in the trabecular bone matrix, while osteocytes, osteoblasts, chondrocytes and bone pits. The important antigen of xenogeneic bone is the surface glycoprotein antigen determined by the major histocompatibility complex MH. After xenotransplantation, antigen uptake, processing, and presentation by helper cells leads to the activation, proliferation, and differentiation of T and B cells, and ultimately cellular immunity and humoral immunity. Both MHC-encoding and non-MHC-encoding antigens can induce the production of anti-graft antibodies.
2 Preparation of xenogeneic bone
The preparation of xenogeneous bone materials is mainly the processing of xenogeneic bone, which is the key link for the success of bone grafting. The goal is to reduce or remove the antigenic components in xenogeneic bone, reduce or eliminate the rejection caused by xenotransplantation, and preserve its ability to induce osteogenesis as much as possible. There are mainly the following types: calcination method: calcination can oxidize and remove all organic matter in the bone, completely eliminate antigens, and retain the original inorganic salt skeleton of animal bones and form a highly porous structure that is suitable for transplantation. The selection of process conditions has a significant impact on the mechanical properties and degradation properties of xenogeneic bone, and its temperature influence is particularly important. It is more beneficial to prepare calcined bone with low knot grade for bone repair, but the mechanical strength of the material may be too low to meet the repair of long bone defects when the crystallization is too low, so there should be a proper balance between low knot grade and high mechanical strength. Freeze-drying method: -30--70 °C preservation of bone graft is a common measure of clinical bone bank, it is generally believed that cryopreservation can reduce the antigenicity of bone grafting, and vacuum drying on the basis of deep and low temperature freezing can further reduce its immunogenicity, which is better than simple decalcification and cryotherapy. However, the clinical application results of lyophilized bone have been mixed. Decalcification method: The decalcification method is to acid treat the xenogeneous bone, and after removing the minerals, there are non-collagen, bone growth factors and collagen complexes, which become the decalcified bone matrix (DBM). DBM has a certain mechanical strength, retains the bioactive components in the bone matrix, and can be tightly bound to collagen in the bone matrix, which can induce the transformation of mesenchymal cells into osteocytes and chondrocytes, and has strong bone induction ability. It is believed that decalcification can release osteogenic inducible factors so that decalcified bone can be replaced by new bone faster, so some decalcified bone has stronger bone induction ability than non-decalcified bone, but although the osteogenic induction activity of completely decalcified bone is good, the inorganic light-based apatite products in natural bone are destroyed, and it is difficult to meet the mechanical requirements of bone tissue engineering for scaffold materials. Deproteinization method: The deproteinization method is to remove the organic matrix, which can eliminate the adverse consequences caused by the difference in histocompatibility between the donor and the recipient, but still retain the ability of bone grafting: the deproteinized bone retains the three-dimensional reticular void structure of the original bone tissue, preserves the porosity, pore size and interpore connection of natural bone, the protein content is very low, and the main components are non-conjunctive phase hydroxyapatite IV composed of calcium and phosphorus. It has certain tensile strength, bending resistance and compression resistance, and its composition and biomechanical strength are different with different treatment methods. The partially deproteinized xenogeneic bone completely retains the inorganic framework and part of the collagen in the raw bone, overcomes the shortcomings of calcined bone brittleness, and avoids the weakness of the poor strength of the collagen bone matrix, and is more widely used as a bone repair scaffold material.
3 Problems faced by xenotransplantation and the study of composite xenogeneic bone
Bone grafting has three biomechanical properties: (1) osteogenesis, which provides cells with osteogenic swimming energy. (2) Bone conduction, providing scaffolds and bridges for host cell tissue growth and precipitation of new bone. (3) Osteoinduction, inducing the differentiation of local mesenchymal cells into osteocytes or chondrocytes. Osteoinduction is the primary purpose of bone grafting. The researchers compounded the deantigenized xenogeneic bone with the osteoactive substance, and the composite xenogeneic bone was born. Complex of xenogeneic bone with bone-forming protein (BMP), complex with autologous red bone marrow, complex with bone matrix gelatin, complex with a variety of growth factors, complex with bone marrow matrix stem cells, etc. It has the dual effects of bone induction and bone conduction, osteinduction substances induce the differentiation of its target cells into bone cells, and bone conduction provides scaffolds for bone growth, which are necessary for xenogeneic bone transplantation, which greatly improves the effect of bone grafting.
In short, now that clinical bone transplantation has entered the era of composite xenotransplantation, there are still many issues worth exploring: such as identifying the interrelationship between bone graft immunity and osteogenic induction, understanding the material basis of the two at the subcellular level: the regulatory network of bone induction factors, etc.: the regulation of bone marrow stromal stem cells, the basic theory and technical methods of induced differentiation, etc.: how to match xenogeneic bone materials, seed cells, and growth factors well, etc., with the deepening of basic and clinical research, Xenotransplantation will be accompanied by the rapid development of bone tissue engineering represented by stem cells, and new progress will be made.
References
[1] Lane JM,Sandhu HS, Orthop clinNorth Am,1987; 18(2):213-225. [2] Liu Wei, Lu Yupu, Hu Yunyu, Immunohistochemical experiments on antigenicity of heterogeneous bone were studied in Chinese Journal of Orthop,1989,91:53-54.
[3] Luo Zhuojing, Hu Yunyu, Wang Qian, Immunohistochemical study of antigen distribution of xenogeneic cancellous bone graft, Chinese Journal of Orthopedics, 1998, 56:539-540.
[4] Cho,Gyunggoo,et al. Detection ofHydroxyl lons in Bone Mineral bySolid State NMR Spectroscopy J. Science,2007,300(5622):1123-1127.
About the Author
Yu Xiaodong (1983-), male, from Changsha City, Hunan Province, holds a master's degree. He is currently working in Changsha Hospital of Traditional Chinese Medicine (Changsha Eighth Hospital). His research interests are trauma orthopedics and microsurgery.