When Dr. Ilizarov performed the distraction osteogenesis (DO) study of the canine leg, he observed that active regeneration of the microvascular network first occurred before the osteogenesis occurred in the interstices of the distraction region of the amputated end, and angiography confirmed the “microvascular and microcirculation” reconstruction in the distraction region of the limb [1,2] [Figure 1]. ” reconstruction [1,2] [Figure 1] with increased blood and blood flow. In recent years, Ilizarov distraction tissue regeneration technique (distraction histogenesis ,DH) has been applied to orthopedic surgery, vascular surgery and other fields to obtain satisfactory results and save some mutilated deformities of lower limbs that were on the verge of amputation, which all belong to the technological progress in the post-Ilizarov era, and at the same time prompted related scholars to make reflections on tissue repair and reconstruction and These are the technological advances in the post-Ilizarov era, and at the same time have prompted scholars to reflect on and boldly explore the techniques of tissue repair and microcirculation reconstruction. Among them, DH technology and the microcirculatory reconstruction technology spawned by it for the treatment of ischemic diseases of the extremities have become a hot topic of attention, which is called “microcirculatory reconstruction in the post-Ilizarov era”.
I. The concept of microcirculation and the application of microcirculation reconstruction in the past
In 1954, the concept of microcirculation was formally introduced in the First International Conference on Microcirculation in the United States, which means the blood circulation of microvessels between micro-arteries and micro-venules. Microcirculation is the place where human cells exchange substances and maintain the metabolism of vital organs, and the development of any disease is ultimately related to the disorder of microcirculation. Diseases related to surgery such as femoral head necrosis, thrombo-occlusive vasculitis, diabetic foot, fascial compartment syndrome, ulcer disease and various traumatic tissue necrosis are closely related to microcirculatory damage. Microcirculation reconstruction means to improve or restore the function of tissues by intervening in the damaged tissues and promoting the repair or regeneration of the damaged microcirculation.
Microsurgery is one of the major innovations in medical technology in the latter part of the 20th century. In recent decades, with the increasing maturity of microsurgical techniques, flap grafting with vascular tissues is a highly respected method for repairing soft tissue defects and reconstructing damaged microcirculation in the limbs with a wide range of indications and definite efficacy. Microsurgical techniques were first pioneered in the fields of plastic surgery and orthopedics to repair traumatic defects in human tissue. In the field of maxillofacial surgery, it is mostly used for the removal and repair of large scale maxillofacial tumors, including soft and bone tissues. In orthopedic surgery, it has greatly contributed to the development and improvement of traumatic orthopedics, especially bone grafting with blood vessels, bone and muscle flap transplantation, soft tissue defect repair transplantation, etc., which mostly belong to the field of emergency trauma and can save limbs or even lives in time. 1962, Chen Zhongwei et al [3] successfully completed the world’s first case of severed hand reimplantation, where the finger arteries and veins were only about 0.8 mm in diameter, which required a high level of microvascular anastomosis technique. In 1972, the orthopedic department of Huashan Hospital in Shanghai completed the world’s first free flap grafting, after which the technique was soon carried out in Shanghai and nationwide with success. In the early 1970s, Chinese and American orthopedic surgeons applied the small vessel anastomosis technique to successfully repair tissue defects in the first phase with iliac inguinal free flap grafts [4,5]. Chinese orthopaedic and hand surgery specialists have also made great contributions to innovation and pioneering in this area [6-9].
Other clinical applications of microcirculatory reconstruction techniques are relatively few and their clinical efficacy is inexact. Some scholars [10,11] applied vascular bypass artery reconstruction to anastomosis of small distal limb arteries for the treatment of thromboembolic vasculitis, which significantly improved microcirculation around the lesion in the early postoperative period, but dynamic follow-up at 12, 14, and 36 months after surgery by Dilege [11] revealed a gradual decrease in microvascular patency. Agarwal [12] treated 273 patients with thromboembolic vasculitis who had failed sympathetic ganglionectomy treatment with a large omental graft fixed to the lesion with satisfactory long-term follow-up. The mechanism of treatment is that the lipid cells of the greater omentum synthesize vascular endothelial growth factor and the microvascular endothelial cells of the greater omentum synthesize basic fibroblast growth factor. These two growth factors have been shown to be powerful pro-vascular growth factors [13], and the large omentum has a rich network of arteries, veins and lymphatic vessels, which can easily establish collateral circulation with surrounding tissues and improve blood supply after transplantation. Stem cells are a class of cells with high self-renewal and strong differentiation potential. It was found that endothelial progenitor cells are not only involved in vascular development during the embryonic period, but also play a role in vascular neogenesis in the adult organism [14]. The use of endothelial progenitor cells transplanted from bone marrow or umbilical cord blood for the treatment of ischemic diseases has been applied clinically. 2002 Tateisi Yuyama [15] et al. first reported the use of autologous bone marrow stem cell transplantation for the treatment of ischemic lower limb vascular diseases with satisfactory results and no adverse effects. In four patients with vasculitis treated with human umbilical cord blood stem cell transplantation, the resting pain in the ischemic limb was relieved quickly and the necrotic skin lesions were healed within 4 weeks.
In conclusion, the reconstruction of microcirculation and the recovery of tissue function are influenced by various factors [17,18], and the previous techniques of microcirculation reconstruction have not actually been widely used clinically except for tissue transplantation, and their exact efficacy remains to be observed in the long term.
The effect of tension on microcirculation reconstruction
Numerous studies have confirmed that mechanical stimulation can promote capillary regeneration and tissue regeneration [19-21], and neovascularization plays a key role in distraction osteogenesis [Figure 2]. Histologically, it was demonstrated that thin capillaries grew between the bone columns during distraction osteogenesis (DO), and vessels of uniform diameter expanded from the surface of the original bone ends, and microangiography confirmed that the neovascularization was in the same longitudinal direction as the new bone [1].Yang et al [22] demonstrated in an experimental study that the osteotomy site remained elastically connected after firm fixation with an Ilizarov external fixator, and that slow distraction caused abnormal tissue metabolic activity and A growth zone can appear in the middle of the lengthening area with fibroblast-like cells forming collagen fibers (arranged in the same direction as the retraction direction), and osteoblasts on the collagen fibers produce bone-like tissue, gradually forming bone trabeculae and gradually ossifying after fixation; active smooth muscle cells appear in the middle layer of the vascular wall, and the new capillaries have many traffic branches and vessels in the soft tissue around the retraction area. The new capillaries have many traffic branches that anastomose with the vessels in the soft tissues around the stretched area, forming the blood circulation between the stretched area and its surroundings.
Immunohistochemical studies of the vascular and blood flow aspects in the stretched area revealed that laminin and type IV collagen, located in the basement membrane layer of the vessel, are closely associated with active vessel growth after stretching. Histological and ultrastructural studies revealed exuberant growth of thin-walled vessels. Angiographic and microangiographic studies also confirmed the presence of a number of sinusoidal vessels, approximately 150-200 um in diameter, flowing from the host bone surface (both epiphyseal and endosteal) to a central fibrous region, wrapped parallel to the perimeter of the nascent bone column. Regional perfusion studies applied scintigraphy to quantify blood flow and found that blood flow was significantly elevated within the subject limb, approximately 10 times more than in the control limb. The site of stretching correlated with the degree of increased blood flow, but the same increase in blood flow was present even in the distal end of the subject limb. In the fracture model, there was a temporary increase in blood flow that peaked about 5 weeks after osteotomy. However, the increase in blood flow during stretching bone growth seems to be different and not temporary, and is generally able to last for at least 17 weeks [23].
III. The advent of microcirculatory reconstruction in the post-Ilizarov era
The classic circular external fixation device in the Ilizarov technique was first applied to save bone defects, infections and deformities after war injuries. From its creation by Dr. Ilizarov in the 1850’s to his death in the early 1990’s, the technique was developed in just over thirty years, and although Dr. Ilizarov discovered the phenomenon of vascular network renewal during distraction osteogenesis, he did not apply the technique in depth in the field of microcirculatory reconstruction. 2012 marks the twentieth anniversary of Dr. Ilizarov’s death (1992). However, as the “law of tension stress” and DO technique, which laid the foundation of Ilizarov technique, have been widely and deeply understood, the application of Ilizarov technique has gone far beyond the traditional treatment of trauma and bone and soft tissue defects, and some new techniques have been created. The application of Ilizarov’s distraction osteogenesis (DO) technique for microcirculation regeneration is one of the important techniques. The application of Ilizarov’s bone transverse distraction technique results in the formation of numerous capillary networks (instead of a few vessels) in the tissue interstices in about three weeks, which is why Ilizarov’s technique is also considered as the “precursor (soulful technique) of tissue regeneration”. According to the DO technique theory, slow and continuous stretching stimulates cell proliferation and biosynthesis, and tissue metabolism becomes active. By giving the bone a suitable stretching stress, the technique is able to mobilize the natural repair potential of the tissues, allowing the simultaneous growth of the bone and its attached muscles, fascia, blood vessels and nerves [24,25], thus achieving the natural reconstruction of the damaged tissue microcirculation. This technique is more minimally invasive than the previous microcirculatory reconstruction methods and conforms to the natural repair and reconstruction rules of tissues, and has unparalleled advantages over the previous repair and reconstruction techniques.
Advantages and clinical application of post-Ilizarov era microcirculatory reconstruction
DH microcirculation reconstruction technique is an expansion of the previous microsurgery technique. The current microsurgery technique can complete the anastomosis of <0.2mm vessels, but only a few small vessels can be anastomosed, while DH technique can stimulate the formation of "vascular network". Therefore, it can be said that the post-Ilizarov era microcirculatory reconstruction has broken through the tissue repair and reconstruction model of destruction before reconstruction, and its effectiveness in clinical application has been proven. vascular network [26] [Figure 3], which effectively reconstructed the microcirculation of ischemic tissue. Qu Long et al [27] [Figure 4] applied the intraosseous bone relocation technique to treat collapsed femoral head necrosis with satisfactory clinical efficacy. The application of cranial bone relocation at the Russian Ilizarov Technical Center for the treatment of chronic cerebral ischemic disorders can effectively improve cerebral microcirculation [24]. Qin Sihe [28] [Figure 5] applied Ilizarov technology to treat crippled deformities of lower limbs on the verge of amputation, and all nine patients preserved the affected limbs and improved the deformity of lower limbs through this technology.
Professor Qin Sihe introduced and digested the biological theory of Russian Ilizarov retraction into tissues [29], carried out a lot of clinical practice, and proposed the theory of natural reconstruction in orthopedics [30], which fits the natural law of tissue repair and reconstruction by itself. The concept of orthopaedic natural reconstruction was proposed to mark the era of natural reconstruction of bone and joint trauma from replacement reconstruction, and Ilizarov technology is the key to open this era. In view of the far-reaching influence of Ilizarov technology on modern external fixation technology, the first Beijing International Conference on External Fixation and Bone and Joint Repair and Reconstruction was initiated and held by Prof. Qin Sihe, Chairman of the International Federation of External Fixation and Bone Reconstruction China (ICEF&BR China) from April 19-22, 2012. In the afternoon of the 21st, a presentation on “Soft Tissue Regeneration and Repair and Microcirculation Reconstruction” was held. The presentations included “History of Bone Lengthening in Japan” by Natsuo Yasui from Japan, “Post-Ilizarov Era – Microvascular Network Reconstruction Technology and Limb Vascular Regeneration and Repair” by Dr. Qu Long, and “Ilizarov Technology to Save the Limb” by Prof. Qin Sihe. “Ilizarov technique for ischemic foot and ankle deformity on the verge of amputation” and “Ilizarov technique combined with tipped flap transfer for the treatment of calf and foot and ankle trauma sequelae” by Prof. Shu Hengsheng, etc. All of them mentioned All of them mentioned the important role of Ilizarov technique for microcirculation reconstruction of limb tissues. Modern external fixation technology represented by Ilizarov technique is quietly bringing a revolution in microcirculatory reconstruction technology, which is widely used in the treatment of various ischemic and traumatic diseases.
V. Prospect and conclusion
What Dr. Ilizarov brings to future generations is not only his technique, but more importantly the concept of natural tissue repair and reconstruction. Any local tissue proliferation or regeneration must be preceded by microvascular regeneration, and the previous microcirculatory reconstructions are still in essence limited by the technology of replacement reconstruction, without the real sense of mobilizing the natural regeneration potential of tissues. However, the more advanced the transplantation technology is, the more it deviates from the natural law of the tissue’s own repair and reconstruction. The microcirculatory reconstruction led by the post-Ilizarov technology era can reduce the indications for microsurgery – free tissue transplantation with vascular tip, expand the treatment scope of some limb ischemic diseases, and clinically save some ischemic lower limb stumps that are on the verge of amputation with safer and more minimally invasive medical procedures. In Russia, this technique is used to treat cerebral ischemic diseases and strokes by pulling and sliding on the outer plate of the skull to stimulate microcirculation reconstruction in the corresponding parts of the brain tissue [18]. Since the Ilizarov microcirculatory reconstruction technique for the treatment of vascular injury and limb ischemic diseases is still short, it is still in its infancy and has a broad prospect of exploration from basic research, surgical indications, surgical methods, medical process control, and efficacy evaluation criteria.
References
[1] Zhang W., Qin S. He. Experimental study on the effect of distraction stress on tissue growth and origin. Lower Extremity Deformity Surgery, Beijing: People’s Health Publishing House, First Edition, 1998:602.
[2] Ilizarov GA. Transosseous Osteosynthesis, Theoretical and Clinical Aspects of the Regeneration and Growth of Tissue. Springer-Verlag, Berlin, 1992.
[10]Dilege S,Aksoy M,Kayabali M,et al. Vascular recon struction in Buerger’s disease:is it feasible[J].Surg Today,2002,32(10):1042.
[11]Bozkurt AK,Besirli K,Koksal C,et al. Surgical treatment of Buerger’s disease [J].Vascular,2004,12(3):192-197.
[3] Chen CW, Joseph Bao, Qian YQ, et al. Replantation of traumatic complete forearm amputation. Chinese Journal of Surgery, 1963,11 :767.
[4] Yang Dongyue. Report of a case of repairing a buccal defect with a vascularized free flap graft. Chinese Journal of Medicine, 1974,54: 163.
[5]Darial RK,Williams HB.The free transfer of skin flaps by microvascular anastomosis.Plast Recoustr Surg,1973,55:177.
[6]Gu YD. Review and prospects of toe transplantation. Chinese Journal of Microsurgery,2000,23:10-11.
[7] Chen ZG. A review and prospect of bone grafting. Chinese Journal of Microsurgery, 2000, 23:15-16.
[8] Cheng G-L. Special types of severed fingers and prospects for replantation. Chinese Journal of Microsurgery, 2000, 23:19-20.
[9] Yang C., Xie H. Q.. The status and application of microsurgical techniques in tissue engineering research. Chinese Journal of Microsurgery,2000,23:21-22
[12]Agarwal VK.Long-term results of omental transplantation in chronic occlusive arterial disease(Buerger’s disease)[J].Int Surg, 2005,90(3):167-174.
[13]Baffour R,Berman J,Garb JL,et al. Enhanced angiogenesis and growth of collaterals by in vivo administration of recombinant bFGF in a rabbit model of acute lower limb ischemia: dose-response effect of bFGF.J Vase Surg,1992,16:181-191.
[14]Hill JM,Zalos G,Halcox JP,et al.Circulating endothelial progenitorcells,vascular function and cardiovascular risk[J].N Eng J Med.2003,348(7 2003,348(7):593-600.
[15]Tateishi-Yuyama E,Matsubara H,Murohara T,et al.Therapeutic angiogenesis for patinents with limb ischaemia by autologous transplantation of bone-marrow cells:a pilot study and a randomized controlled trial[J].Lancet,2002,360(93310;427-435.
[16]Kim SW,Han H,Chae GT,et al.Successful stem cell therapy using umbilical cord blood-derived multipotent stem cells for Buerger’s disease and ischemic limb disease animal model[J].Stem Cells,2006,24(6):1620-1626.
[17]Terumi Sakurai,Naohito Terui.Effects of sympathetically induced vasomotion on tissue-capillary fluid exchange.Am J Physiol Heart Circ Physiol Am J Physiol Heart Circ Physiol ,2006,291:1761-1767.
[18]Hayek L,Culler FL,Beattie GM,et al.An in vivo model for study of the angiogenic effects of bFGF.Biochem Biophys Res Cummun,1987,147:876-880.
[19]Akiko Mammoto,Kip M.Connor,Tadanori Mammoto,Chong Wing Yung,et al.A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature,2009, 457(26):1103-1108.
[20] Herzenberg JE, Waanders NA.Calculating rate and duration of distraction for deformity correction with the Ilizarov technique[J]. Orthop Clin North Am. 1991 22(4):601-11.
[21] Steinwender G, Saraph V, Zwick EB, et al. Complex foot deformities associated with soft-tissue scarring in children[J]. J Foot Ankle Surg. 2001 Jan-Feb;40(1):42-49. [22] Yang L, Nayagam S, Saleh M. Stiffness characteristics and inter-fragmentary displancements with different hybrid external fixators.Clin Biomech,2003,18(2):166- 172.
[23] Zhuang Qianyu,Weng Xisheng,Qin Sihe.Advances in basic and clinical application of Ilizarov technique. Chinese Journal of Orthopaedics,2012,32(3):277-282.
[24] Qin Sihe. Overview of Ilizarov technique. Chinese Journal of Orthopaedics,2006,26(9):642-645.
[25]Barker KL,Lamb SE,Simpson AH.Functional recovery in patients with nonunion treated with the Ilizarov technique.J Bone Joint Surg Br,2004,86(1): 81-85
[26]Qu L,Wang A-L,Tang F-G. Thrombo-occlusive vasculitis treated with tibial transverse transfer revascularization. Chinese Medical Journal,2001,81(10):622-624.
[27] Qu L, Li KG, Du ZHAOhui, et al. Treatment of femoral head necrosis by endosteal bone transfer method. Chinese Journal of Surgery,2008,46(2):156.
[28] Qin Sihe,Chen Jianwen,Zheng Xuejian. Modified Ilizarov technique for the treatment of crippled deformities of lower limbs on the verge of amputation. Chinese Journal of Orthopaedics,2010,30(4):423-426.
[29] Qin Sihe, Ge Jianzhong, Guo Baofeng. The origin and Chinese expression of “distraction osteogenesis” and “distraction tissue regeneration” techniques. Chinese Journal of Surgery,2012,50(5)
[30] Qin Sihe. Ilizarov technique and the concept of natural reconstruction in orthopaedics. Chinese Journal of Orthopaedic Surgery,2007,15(8):595 -596.