Xiong Chen (review), Dong Yin (revised)
Funds: Guangxi Key R&D Program (No.: Guike AB16380230)
[Abstract] At present, bone grafting is an important means for the treatment of bone defects caused by various reasons, and how to accelerate bone healing and reduce complications will be an important topic that needs to be solved urgently in clinical application. This article reviews the research progress of autologous bone transplantation and allogeneic bone, as well as the experimental research and clinical application of combined bone transplantation, and expounds the advantages and feasibility of combined bone transplantation.
1674-3806(2018)03-0307-04doi:10.3969/i.issn.1674-3806.2018.03.31
Progress in the study of autogenous bone graft intermingled with bone allograftCHEN Xiong,YIN Dong
Guangxi Medical University, Nanning 530021,China[ Abstract ]At present, bone transplantation is an important method for treatment of various causes of bonedefects. How to aceelerate bone healing and reduce complications remains a thorny problem, also an urgent and unre.solved issue. The clinical application of autogenous bone grat and bone allograt , and the research progress of autogenous bone graft combined with allogeneie bone transplantation are reviewed in this paper, and the advantages and thefeasibility of the combined bone graft are expounded.
Key words]Autologous bone: Allogeneie bone: Bone defect;Combined transplantation
For more than 300 years, bone grafting has been widely used in orthopedic clinics. Autologous bone grafting refers to the surgical method of obtaining fresh bone tissue from another part of the patient's body and transplanting it to the bone defect, and autologous bone grafting does not cause rejection. Autologous osteochondral transplantation can provide intact hyaline cartilage and better restore the structural, biomechanical and functional properties of articular cartilage, especially autologous iliac bone is the preferred bone graft", but autologous bone materials are limited. Allogeneic bone grafting refers to a surgical method in which the same non-autologous bone tissue is obtained and transplanted to a bone defect. Both autologous bone and allogeneic bone grafting have their own advantages and disadvantages, and if the two are used together in clinical practice, their shortcomings can be overcome and their advantages can be maximized. At the beginning of the 19th century, Walther replanted the annularly excised skull, which was the first bone graft in clinical practice. After autologous bone grafting, most of the bone tissue is dissolved and resorbed, and only the periosteum, bone marrow, and bone tissue on the surface of the grafted bone survive. The autologous bone cortex had vascular invasion after 6 days of implantation, and the blood supply could be completely restored after 1~2 days. Autologous cancellous bone implantation was surrounded by hematoma for 2 days, and blood supply was restored after 2 weeks!. Thus, it can be seen that bone cancellous is easier to repair bone defects. As early as 1881, Macewen was the first to report his success in bone grafting. In 1908, Lexer performed allogeneic joint transplantation, which laid a reliable foundation for the development of modern allogeneic bone transplantation in clinical applications. With the advancement of science and technology, allogeneic bone transplantation has been widely used in clinical practice to repair bone defects caused by trauma, infection and tumor, thereby greatly preserving the integrity and function of the affected limb and improving the quality of life of patients. This article reviews the results of recent basic and clinical research on bone transplantation.
1 Autologous bone grafting
Autologous bone is the most traditional and effective bone graft material, which has the advantages of good biocompatibility, strong osteogenic ability, and high osteoinduction activity, and is the most commonly used material for the treatment of bone defects in clinical practice. From a biological point of view, the ideal bone graft material should provide three factors at the same time: bone conduction matrix, osteinduction factors, and osteogenic cells. Autologous bone grafting is widely used in clinical practice because it meets all the characteristics, and autologous bone is still the gold standard for bone grafting, including cancellous bone, cortical bone, and bone marrow transplantation. As a conventional donor area for autologous bone transplantation, the iliac bone has a large number of active hematopoietic bone marrow cells, which have a positive effect on bone healing. 4。 Autologous bone grafting also plays an important role in major orthopedic joint surgery. From the perspective of cell biology, fracture healing requires some osteocyte secretion inducing factors at the fracture end to stimulate the growth of bone and microvasculature, and there are many factors in autologous bone that can induce bone growth, and some studies have shown that epidermal growth factor EGFL7 promotes fibroblast and vascular migration by enhancing cell adhesion, strengthens the cytoskeleton, and reduces cell-to-cell aggregation7. Materials other than autologous bone cannot obtain satisfactory therapeutic effects because they only have bone-guiding activity and lack osteoinductive activity". When some bone defects are large, autologous bone resection will inevitably increase additional trauma and operation time, and a series of complications may occur in the donor bone area after surgery, including infection, blood loss, hematoma, nerve damage, deformity, chronic persistent pain, etc., with a ., incidence of up to 20% [1.13][14.1S] and increased operation and hospital stay. Therefore, although autologous bone is good, it is affected by many factors such as limited autologous bone mass, so it is necessary to consider finding other bone grafting alternatives or bone grafting with some allogeneic bones. The advantages of donor collateral injury caused by autologous bone transplantation make allogeneic bone a common material for clinical repair of bone defects, but allogeneic bone transplantation also has deficiencies such as disease transmission, fracture, nonunion, and delayed union. In view of these shortcomings, we can synthesize and explore more in-depth joint research and exploration in the application of allogeneic bone in the treatment of bone defects in the future, and find better bone grafting methods.
2 Allogeneic bone grafting
With the passage of time, when autologous bone grafting cannot meet the needs of human bone defect surgery, allogeneic bone grafting technology has gradually developed and many bone banks have been established, and the clinical application of allogeneic bone is increasing. However, compared with autologous bone grafting, allogeneic bone grafting has more limitations in bone grafting performance, and there are still some controversies about the mechanism of bone healing. In the repair of large bone defects, traditional allogeneic bone transplantation also faces the problems of slow replacement of new bone and poor biomechanical properties. Guo et al. [6] pointed out that allogeneic bone grafting has a definite effect in the treatment of bone defects. However, allogeneic bone has disadvantages such as the transmission of bloodborne diseases, immune responses, and bone healing. In addition, allogeneic bone only has bone conduction but no bone induction, and fracture healing may be relatively slow after transplantation. Allogeneic bone grafting can play a certain role as a scaffold in the treatment process, support fracture reduction, and have a certain effect of bone induction activity!7 Zuo Jian et al. (8) expounded the shortcomings of allogeneic bone grafting in the application status of allogeneic bone grafting for the repair of bone defects: bone marrow tissue, osteoblasts, osteoclasts, blood cells, and the cell matrix of nerve fibers and pedicle tissues in bone tissue all have certain antigenicity, among which bone marrow is the strongest, bone cells are second, and bone matrix is the weakest. Allogeneic frozen bone transplantation can also elicit an immune response, but chronic rejection is the main cause, and they also believe that the immune response caused by the difference in leukocyte antigens between donors and recipients is the main cause of frozen bone graft failure. Bi Zhiwei and so on!" In the study of allogeneic bone transplantation in the treatment of bone defects, it is explained that allogeneic bone has the advantages of sufficient bone tissue source, similar structure to autologous bone, significantly weaker rejection than xenogeneic bone, and no secondary injury to the donor site caused by autologous bone transplantation, which makes allogeneic bone a common material for clinical repair of bone defects, but allogeneic bone transplantation also has the advantages of disease transmission, fracture, nonunion, delayed healing, etc. In view of these shortcomings, we can synthesize and explore more in-depth joint research and exploration in the application of allogeneic bone in the treatment of bone defects in the future, and find better bone grafting methods.
3 Overview of autologous bone combined allogeneic bone grafting
Autologous bone is the best material for bone grafting, but its material source is very limited, and the expected results cannot be achieved in some surgeries with large bone defects. Allotogeneic bone material has a rich source, and because of its natural structure, shape and strength, it has a certain induction activity, allogeneic bone makes up for the defects of autologous bone in terms of material extraction, but at the same time, it has the risk of immune rejection, which can lead to adverse reactions such as bone resorption at bone defects, delayed bone healing, and bone nonunion. In recent years, there have been clinical studies on the combined application of autologous bone and allogeneic bone as bone graft materials.
3.1 Experimental studies The generation of new bone in bone grafting is a complex process that requires the activation, migration, differentiation and maturation of various cells, and the synthesis of extracellular matrix and various morphological structures [201]. Early studies have shown that some cytokines, such as bone morphogenetic protein (BMP-2) [2], basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF-1), are beneficial to bone tissue growth!22]. There is an osteoblast in bone tissue that recruits osteoblasts or their progenitor cells from adjacent tissues and blood circulation to the site where osteogenesis will occur, and then the cells proliferate and differentiate into mature functional osteoblasts. Thus, the aggregation of osteoblasts or their progenitor cells at the site of the bone defect is a prerequisite for new bone formation [21]. It was found that osteoclasts and osteoblasts secreted EGFL7 to promote vascular migration and formation, and osteoblasts specifically secreted EGFL6, which had a specific effect on local blood supply. Mesenchymal stem cells (MSCs) share the commonalities of stem cells, as well as the ability to self-renew, differentiate in multiple directions, and homing to multiple types, including osteogenesis, cartilage, and adipocytes [4]. Zhang Xuejun [25] studied the general histological changes in healing after allogeneic bone grafting by general histological observation, tetracycline fluorescent labeling, and BMP immunohistochemical staining through animal experiments: to observe the participation of the Harvard system in allogeneic bone osteogenesis and reconstruction, and to observe the activity of BMP after allogeneic bone grafting. The conclusions are as follows: (1) the healing process after allogeneic bone grafting is completed in allogeneic bone resorption and creeping substitution; (2) osteogenic activity around allogeneic bone is carried out by soft tissue infiltration and formation of bone resorption pits; (3) There is a certain amount of BMP activity in allogeneic bone after allogeneic bone transplantation; (4) Bone metabolic activity after allogeneic bone transplantation is carried out in the Harvard system four weeks after transplantation. Although a large number of allogeneic bone grafts can cause early immune rejection, mixing allogeneic bone with autologous bone will reduce rejection and achieve a stronger fusion effect. In addition, there are viable osteocytes and inducing factors in autologous bone, which can effectively promote bone production and complete bone repair.
3.2 Clinical application research: osteonecrosis of the femoralhead (ONFH) is a common and refractory disease in orthopedics, and there is a consensus among experts at home and abroad on the main aspects of diagnosis and treatment (26.271 In addition, in recent years, people's requirements for their own quality of life have increased, resulting in the rejuvenation of artificial total hip replacement in clinical practice, followed by an increase in hip revision [2]. However, in order to overcome bone defects during joint revision, the simple use of autologous bone to fill bone defects is limited to a small number of defects, and although the simple application of allogeneic bone grafting is widely used [29], it is immunoreactive and expensive, so a single bone graft has its own advantages and disadvantages. In recent years, in order to overcome the problems in clinical practice, the application of autologous bone combined with allogeneic bone to repair bone defects has achieved certain results. A large number of fractures and defects, such as compression of bone and interspinal fusion, are also common in spine surgery. At present, the autologous bone and allogeneic bone used in clinical practice to fill bone defects and allogeneic bone interbody fusion have all problems such as bone defects, and some investigators have compared the use of autologous bone and allogeneic bone between the same spine, and the results suggest that the efficacy of allogeneic bone grafting and autologous bone grafting is similar, but due to the small sample size of the study and the short follow-up time, there is no significant difference in the short term [3]. Mixed bone grafting of autologous bone and allogeneic bone as bone grafting material after spinal tuberculosis surgery has been shown to be feasible [21]. Zhou et al. [33] used allogeneic bone combined with autologous bone in the surgical treatment of thoracolumbar fractures, and the results showed that hybrid bone grafting was an ideal bone grafting method for restoring the height and shape of the injured vertebrae and reconstructing the physiological structure of the spine. In clinical practice, bone defects caused by resection of some tumors, major trauma, and infection are also common. Zhang Xiyan [34 clinical observation studies on 46 patients treated with allogeneic bone and autologous bone mixed grafting for benign bone tumors showed that allogeneic bone and autologous bone mixed grafting has the advantages of promoting bone healing, bone formation, convenient use, reliable bone grafting, and fewer complications in the treatment of benign bone tumors. Tan et al. proposed in the case analysis of bone grafting of benign limb tumors that autologous bone integration allogeneic bone grafting is an effective method for the treatment of benign bone tumors of the limbs. Li Shaoping [3] also affirmed the efficacy of hybrid bone grafting in the treatment of benign tumors of the limbs. Therefore, the efficacy of combined bone grafting for bone defects after bone tumor surgery is relatively obvious, and it is worth promoting and applying in clinical practice. Huang Qilong et al. [37] used autologous and allogeneic bone 2:1 combined implantation to treat distal tibial bone defects with infection, and the results suggested that autologous bone combined with allogeneic bone open bone grafting is a simple and effective method for the treatment of large distal tibial infectious bone defects, and its efficacy is certain, which can significantly shorten the fracture healing time and reduce the pain and economic burden of patients.
4. Outlook
In recent clinical studies of bone grafting, the application of allogeneic and autologous bone combined bone grafting has been gradually carried out. According to the healing process of allogeneic bone, the peripheral blood vessels, interstitium, and tissues continue to grow into the formation of new bone, and the allogeneic bone is separated, interspersed, and gradually wrapped around the process of replacement, which is in line with the principle of bone infiltration, and the osteogenic process is carried out from the periphery of the bone graft area to the center, and finally completes the repair. The speed of bone infiltration is closely related to the rate of revascularization of the grafted bone and the formation of new bone!8]. If the two are combined, there should be good advantages: (1) overcoming the shortcomings of limited autologous bone extraction. (2) Effectively reduce the infection rate of allogeneic bone grafting, delayed union, non-healing fracture and the incidence of traumatic arthritis. (3) There are related factors in autologous bone tissue, which promote the formation of local blood vessels, further induce osteogenesis, and promote bone healing faster. (4) Accelerate the bone healing time when allogeneic bone grafting is used alone. (5) Reduce the cost of using allogeneic bone alone. (6) The combined compression of autologous bone and allogeneic bone can fully combine the two with a large number of autologous bone centers, which can well induce and promote bone production. Therefore, theoretically, allogeneic and autologous bone grafting can highlight their advantages, which has far-reaching significance for the progress of bone grafting.
References
1. Lareau CR,Deren MÉ,Fantry A,et al. Does autogenous bone graftwork? A logistic regression analysis of data from 159 papers in the footand ankle literature[J]. Foot Ankle Surg,2015,21(3):150-159.
2. Hu Yunyu, Sun Lei, Liu Jian, et al., Clinical application of establishing allogeneic bone bank and bone preparation[J].Chinese Journal of Surgery,1996,34(8):464-468.
3. Chen Xiangyun, Huo Lili, Wang Yanbin. Effect of autologous bone grafting in acetabular defect in total hip arthroplasty[J], Chinese Journal of Clinical Research, 2016, 29(12):1697-1699.
4. Chiodo CP, Hahne J, Wilson MG ,et al. Histological differences in iliacand tibial bone graf[J]. Foot Ankle Int,2010,31(5):418-422.
5. Cao Hong, Zou Haibing, Qian Wei, et al. Autologous bone grafting for the repair of medial tibial plateau inclusive bone defect in primary knee arthroplasty[J].Biological Orthopedic Materials and Clinical Research,2015.12(6):20-22.
6. Sasso RC,Williams Jl, Dimasi N, et al. Postoperative drains at the0donor site Of iliac-crest bone gra£[ J]. J Bone Joint Surg,1998,80(5):631-635.
7. Yang RH, Qi SH, Ruan SB,et al. EGFL7-overexpressing epidermal7stem cells promotes fibroblast proliferation and migration via mediatingcell adhesion and strengthening cytoskeleton[ J]. Mol Cell Biochem ,2016,423(1-2):1-8.
8. Cosso MG , de Brito RB Jr, Piattelli A,et al. Volumetrie dimensionalchanges of autogenous bone and the mixture of hydroxyapatite and au-togenous bone graft in humans maxillary sinus augmentation. A multi.slice tomographic study[ J]. Clin Oral Implants Res ,2014 ,25( 11 ):
9. Liu Hui. Observation on the treatment of benign bone tumors with allogeneic bone and autologous bone mixed transplantation[J].Basic and Clinical Oncology,2012,25(3):229-230
10. Zhang Yang, Chen Jianchang. Comparison of clinical efficacy of lumbar interbody fusion between autologous bone and allogeneic bone[J].Chinese Journal of Bone and Joint Injury,2012,27(1):20-22.)
11. Ding Shuwei, Xu Xuezhen, Zhang Shouqiang, et al. Efficacy of autologous bone or allogeneic bone grafting combined with interlocking intramedullary nail fixation in the treatment of nonunion of femoral shaft[J].Chinese Journal of Bone and Joint Injury,2013,28(6):565-566.)
12. Lad SP, Nathan JK,Boakye M. Trends in the use of bone morpho.12genetic protein as a substitute to autologous iliac crest bone graftingfor spinal fusion procedures in the United States[ J]. Spine ,2011 ,36(4):E274-E281.
13. Skeppholm M, Olerud C, Pain from donor site after anterior cervical13fusion with bone graft: a prospective randomized study with 12months of follow-up[J]. Eur Spine J,2013,22(1): 142 - 147.14
14. Landriel FA, Hem S, Goldschmidt E, et al. Polyetheretherketoneinterbody cages versus autogenous iliac crest bone grafts with anteriorfixation for cervical dise disease[ J]. J $pinal Disord Tech ,2013 ,26(2):61-67.
15. Faldini C , Miscione MT, Acri F, et al, Single level cervical fusionby an anterior approach using autologous bone graft influences theadjacent levels degenerative changes: elinical and radiographie results at 10-year minimum follow-up[J]. Eur Spine J,2012,21(1):90-93
16. Guo Junfang, Huang Haiming, Zhang Jian, et al. Application of allogeneic bone grafting in internal fixation of type A femoral shaft fracture[J].Chinese Journal of Bone and Joint Injury,2015301(6):639-640.)
17. Ngoma AM ,lkeda K, Hashimoto Y,et al. lmpaired regulatory 'T cel!17reconstitution in patients with acute graft-versus-host disease and cytomegalovirus infection afer allogeneie bone marrow transplantation[J]. Int J Hematol,2012,95(1):86 -94.
18. Zuo Jian, Kang Jianmin, Pan Le. Current status of the application of allogeneic bone grafting for bone defect repair [I1, Chinese Journal of Tissue Engineering Research, 2012.16(18):3395-3398
19. Zhiwei Bi, Dong Huang, Haiyang Ouyang, Research progress on the application of allogeneic bone grafting in the treatment of bone defects[J].Chinese Journal of Clinical Anatomy,2014,32(5):623-625
20. Wraighte P] ,Scammell BE. Prineciples of fracture healing[ J]. Surg ,2006,24(6):198-207.
21. Marupanthorn K, Tantrawatpan C, Kheolamai P, et al. Bone mor-.phogenetie protein-2 enhances the osteogenie differentiation capacityof mesenchymal stromal cells derived from human bone marrow andumbilical cord[J]. Int J Mol Med, 2017,39(3):654-662.
22. Wada Y,Kataoka H, Yokose S, et al. Changes in osteoblast pheno-typeduring differentiation of enzymatically isolated rat calvaria cells[J]. Bone,1998,22(5):479-485.
23. Caplan Al. Adult mesenchymal stem cells and the NO pathways[ J]Prc Natl Acad Sci US A.2013.110(8):2695 -2696.
24. Xuejun Zhang, Clinical and immunological observation of allogeneic bone transplantation and animal experimental study of bone regeneration after transplantation 25[D].Soochow University,2004.
25. Powell C ,Chang C,Gershwin ME. Current concepts on the pathogen-esis and natural history of steroid-induced osteoneerosis [ J]. ClinRev Allergy lmmunol,2011,41(1):102 -113.Weinstein RS. Glucocorticoid-induced osteonecrosis[ J]. Endocrine ,2012,41(3):102 -113.
26. Wu Bo, Li Peijia, Sun Lei, et al. Clinical analysis of 45 cases of artificial hip revision surgery[J].Journal of Practical Medicine,2013,30(12):1078-1079.
27. Li Qiang, Liu Min, Shen Minren, et al. Application of allogeneic bone grafting in hip revision acetabular 29 bone defect reconstruction[J].Journal of Traditional Chinese Medicine,2013,28(4):501-502.)
28. Chen Lichun. Observation on the short-term efficacy of autologous iliac mixed allogeneic bone compression bone grafting in the treatment of femoral head necrosis[J].Journal of Changzhi Medical College,2014,28(6):433-435.31
29. Zhi Liu, Meng Wei, Wenben Liao, Allogeneic bone and autologous bone posterior lumbar Cage interbody fusion in the treatment of lumbar degenerative diseases[J].Chinese Journal of Orthopedic Clinical and Basic Research,2015,7(5):290-293.
30. Chen Yongzhong, Wang Jianhuo, Zhang Peng, et al. Journal of Clinical Orthopedics,2014,17(6):626-628.
31. Zhou Fei, Wei Lihong. Clinical study on the treatment of thoracolumbar fracture with allogeneic bone combined with autologous bone in the treatment of thoracolumbar fracture with pedicle in the vertebral vertebrophylle[J], Chinese Journal of Bone and Joint Injury, 2014.2(1):12 -14.
32. Xiyan Zhang, Mixed transplantation of allogeneic bone and autologous bone in the treatment of benign bone tumors in 46 clinical 34 beds[J], Chinese Journal of Practical Medicine, 2011, 6(31):106-107.
33. Li Shaoping, Yang Guangyong, Pan Jichun, Effect of allogeneic and autologous bone transplantation in the treatment of bone defects after surgery for good 36-type bone tumors of limbs[J].Everyone's Health(Late Edition),2015.4(2): 95.
34. Huang Qilong, Ke Yongping, Guo Weizhong, et al. Efficacy of autologous bone combined with allogeneic open bone grafting in the treatment of distal tibial infectious bone defects[J], Chinese Journal of Bone and Joint Injury, 2014, 29(10):1060-1061.
35. Sterenson S, Fmery SE , Goldberg VM, Factors affecting bone graft38incorporation[J]. Clin Orthop,1996,(324):66 -74.