Degenerative spine diseases, especially cervical and lumbar degenerative diseases, are common and frequent in the middle-aged and elderly population, and their incidence has been increasing year by year in recent years, with a trend of rejuvenation. Spinal fusion is safe and reliable and has become a common method for treating these diseases, including anterior fusion, posterior intervertebral fusion, small joint fusion, and interlaminar fusion. Interbody fusion is an emerging method of fusing vertebral bodies, which aims to relieve nerve compression and restore the height of the intervertebral foramen and the normal physiological curvature of the spine. The intervertebral fusion device provides early anterior column stability and creates good biomechanical conditions for intervertebral osteogenesis, thus significantly increasing the intervertebral fusion rate while reducing complications. A variety of materials and structures of intervertebral fusion devices have been widely accepted for cervical and lumbar instability, slippage and disc disease for which conservative treatment has failed. Among them, homogeneous allogeneic intervertebral fusion devices have received more and more attention for their good osteogenic activity and clinical efficacy. The research progress and clinical application of allogeneic intervertebral fusion devices are reviewed. Introduction to the development of intervertebral fusion Badgy and Kuslich were the first to design an intervertebral fusion device, the BAK (BagbyandKuslich) system, for human use in the treatment of degenerative lower back pain. The fusion was filled with autogenous bone and implanted into the intervertebral space, which was then fixed with plates or pedicle nails to maintain the height of the intervertebral space, restore anterior mid-column support, increase intervertebral foramen capacity, relieve nerve root compression, and reduce intervertebral space collapse and pseudoarthrosis formation. Since then, with the development of spinal biomechanics and the widespread use of interbody fusion, cervical and lumbar interbody fusion devices have developed rapidly, and there is an increasing variety. The existing types of intervertebral fusion materials include titanium alloy, carbon fiber, polyether ether ketone (PEEK), and absorbable biomaterials. Due to the limitations of the materials themselves, the prepared intervertebral fusion devices all have their own drawbacks. Wang et al. reviewed the clinical data of 64 patients with anterior cervical fusion using titanium BAK fusion devices and found that the intervertebral height was gradually lost over time, nine patients experienced fusion subsidence, and two patients even required reoperation. It is evident that titanium BAK fusion is not an ideal choice for long-term maintenance of interbody height and physiological curvature of the spine. In addition, studies have shown that metal fusion devices are more likely to sink in osteoporotic patients, which may exacerbate neurological compression symptoms. Carbon fiber has a modulus of elasticity closer to that of normal bone tissue, but is biocompatible and can produce small debris and cause sterile inflammation with long-term use. Resorbable biomaterial fusion devices are mostly made of polylactic acid, whose degradation products create a local acidic environment, which is not conducive to osteogenesis. In addition, the absorption time of resorbable biomaterials often does not match the osteogenesis time of the human body and can easily fail before the vertebral body reaches osseointegration, resulting in a decrease in the vertebral space.PEEK materials are mechanically strong, inert, biocompatible, and flexible in processing, and are currently the most widely used intervertebral fusion device material for clinical applications. However, as a polymeric material, it is not resorbable and can only exist as a foreign body in the intervertebral space, occupying the space required for fusion of normal bone tissue, which may affect the fusion speed and mechanical strength. lee et al. observed 49 fused segments using PEEK fusion for posterior lumbar fusion, and the results suggested that the PEEK fusion formed a solid fusion late after surgery. Because of these material shortcomings, there is a clinical need for an interbody fusion device with strength close to bone and good osteoconductivity and osteoinductivity. Therefore, homogeneous interbody fusions have received increasing attention. The principle and development of allogeneic intervertebral fusion device In 1908, Axhausen proposed the theory of “creeping replacement”, which is still used today, that the grafted bone has osteogenic activity, provides an osteogenic environment and scaffolding for new bone formation, and the new bone tissue can grow along its surface while the grafted bone gradually degrades and is completely replaced by new bone. The new bone tissue grows along its surface while the graft gradually degrades and is completely replaced by new bone. Allogeneic bone used in clinical practice includes cancellous and cortical bone, both of which have a natural three-dimensional mesh structure and are rich in various growth factors required for osteogenesis, with both osteoconductive and osteoinductive advantages, and can be replaced by crawling. The fusion rate of intervertebral implants made of cancellous bone alone ranges from 46% to 90% and is prone to postoperative gap loss, requiring additional biomechanical support from internal fixation such as anterior plates or posterior pedicle nails. The intervertebral fusion device made of allogeneic cortical bone can provide axial support for the anterior column while preserving good osteogenesis and avoiding intervertebral space loss. Biomechanical principles of allogeneic bone intervertebral fusion Allogeneic bone is usually obtained within 24 h of donor death, processed immediately, and preserved by fresh freezing or freeze-drying. After allograft transplantation, new bone formation at the graft site is promoted primarily through osteoconduction and osteoinduction, and the graft bone gradually degrades until it is completely replaced by new bone. Immune rejection is a major obstacle to the survival of allogeneic bone, and the reduced antigenicity of bone after cryopreservation can greatly reduce the incidence of immune rejection. Deep cryopreservation (-80°C) is currently recommended. At this temperature, the enzymatic activity basically disappears, which has a certain effect on reducing immunogenicity, and the mechanical strength remains unchanged, allowing the preservation of homogeneous bone for several years. The mechanical stability of the intervertebral fusion device is mainly derived from the bracing-compression effect and the interface load equalization effect. After implantation of the intervertebral fusion, the bracing force puts the soft tissues around the fused segment under continuous tension, and the fused segment and the fusion device achieve three-dimensional super-static fixation, obtaining anti-shear and rotational effects and exerting self-stabilization, so that the intervertebral fusion device can provide immediate and early fusion stability to the spine. In addition, the intervertebral fusion device serves as an anatomical scaffold, i.e., it restores and maintains the physiological curvature of the spine, enlarges the intervertebral foramen, and relieves nerve root compression by restoring the height of the intervertebral space and reestablishing the mechanical and anatomical stability of the anterior mid-spine. Early annular allograft intervertebral fusion Early allograft intervertebral fusions were simply annular fusions formed by simple processing of long bones such as allograft fibula and femur.Liljenqvist et al. reported the results of 41 patients with an average follow-up of 30.6 months using an allograft femoral annular intervertebral fusion with an average fusion rate of 95% and an average fusion time of 8.7 months. Janssen et al. treated 137 patients with an allograft femoral ring and had a mean follow-up of 18 months, with 94% of patients achieving solid fusion. They concluded that homogeneous bone provides a satisfactory biological environment. However, due to the shape and size of the femoral ring, it can only be used for anterior interbody fusion and is mostly used in the lumbar spine. Slosar et al. used an allograft fibular ring filled with BMP-2 autologous bone for anterior lumbar fusion in patients with disc degeneration, slipped vertebrae, and degenerative scoliosis, and all patients (45 patients/103 segments) achieved intervertebral fusion at 6 months postoperatively. fusion with no serious complications. Because of the good osteogenic activity of autologous iliac bone, the fusion rate and clinical efficacy obtained are regarded as the gold standard for evaluating interbody fusion, so the results compared with autologous iliac bone are important for clinical work. In a semi-randomized, prospective, controlled study using a homogeneous allogeneic fibular ring and autologous iliac bone in anterior cervical fusion, although intervertebral fusion was delayed in the fibular ring compared with the autologous iliac bone (63.1% fusion rate of the fibular ring at 6 months compared with 89.2% of the autologous iliac bone), the fusion rates were comparable at 24 months and there was no difference in the incidence of fusion device descent. Therefore, the allograft fibular ring is a suitable alternative to the autologous iliac bone in anterior cervical fusion. The above-mentioned allogeneic bone intervertebral fusion device is not designed to fit the anatomical shape of the intervertebral space and has a small contact surface with the endplate, which is prone to cutting the endplate due to stress concentration, resulting in increased complications such as fusion drop or withdrawal and pseudoarticular formation; the allogeneic bone ring is processed according to natural materials and has problems such as irregular specifications, large differences in mechanical strength, often too large or too small in size, and inconvenient handling of the natural shape. It is difficult to meet the needs of standardized surgical operations, especially the trend of minimally invasive spinal surgery. In response to the shortcomings of simple fibular rings and femoral rings, anatomical allograft interbody fusion devices that conform to the anatomical characteristics of the intervertebral space are gradually being used for intervertebral fusion. The main design features of these fusion devices include: the upper and lower surfaces have a certain convex curvature, which matches the slightly concave anatomical appearance of the end plate; the contact part with the end plate of the vertebral body is rough or serrated, which increases the contact area with the end plate and is not easily dislodged posteriorly; the design and production of some fusion devices also take into account the anterior convexity of the cervical and lumbar spine; the formation of a series of products with standardized shape and complete specifications, equipped with special The fusion device is equipped with special instruments. Barnes et al. and Arnold et al. reported a homogeneous intervertebral fusion device for posterior fusion, which is made of two pieces of cortical bone with a tooth-like projection on the upper and lower surfaces, and two fusion devices are implanted in the intervertebral space in parallel. In a multicenter prospective study, the clinical results of the anatomic allograft intervertebral fusion were confirmed in a controlled study with the PEEK fusion, with a fusion rate of 95.2%, significant improvement in the Oswestry dysfunction index, no significant difference in comparison with the PEEK fusion, no significant decrease in the vertebral space, and no serious complications such as vertebral slippage or loosening of the internal fixation . Another evidence-based study also confirmed that anatomic allograft intervertebral fusion had the same fusion rate and clinical outcomes as the PEEK fusion. The anatomic allograft interbody fusion is made by cutting and shaping cortical bone, and the shape can be designed and manufactured as needed. Therefore, the scope of application is not limited by the size and appearance of the raw material, making maximum use of the limited allograft bone material. In one study, an anatomical interbody fusion made of femoral cortical bone was used for anterior cervical fusion and compared with a fusion of fibular cortical bone origin. After 12-month follow-up, although there was no significant difference in the visual analogue score (VAS) of pain and the cervical dysfunction index (NDI), the femoral fusion formed fusion earlier than the fibular fusion, while the femoral fusion showed slightly less subsidence than the fibular fusion; in addition, CT examination revealed morphological changes (fracture or fragmentation) in both femoral and fibular fusions in varying proportions, with incidences of 10.8% and 53.2%, respectively. Since fusion devices such as PEEK and carbon fiber rarely fragment, the occurrence of fragmentation of homogeneous bone intervertebral fusion devices is of concern. The reason for less fragmentation of the femoral fusion may be that the femur and fibula have the same density, but the strength index of the femur is greater than that of the fibula; the femoral cortical bone is thicker and has greater compressive strength. Of course, this condition may also be a normal phenomenon in the process of resorption of homogeneous allograft bone and formation of new bone. Although the fusion rate in this report was satisfactory and there were no serious complications, it is worthy of further observation and study to see whether there will be long-term complications with longer follow-up time. Clinical applications of allogeneic intervertebral fusion devices Indications Allogeneic intervertebral fusion devices are suitable for use in almost all conventional fusion devices made of metal or synthetic materials. Take cervical interbody fusion as an example: the indications for clinical application of cervical interbody fusion are neurogenic cervical spondylosis, degenerative cervical segmental instability, and spinal cord cervical spondylosis with non-multi-segmental compression (more than 3 segments) that have failed conservative treatment. In terms of contraindications, Harcker et al. emphasized that when patients have osteoporosis, homogeneous bone intervertebral fusions are as prone to decline as fusions of other materials, and therefore are not suitable for patients with severe osteoporosis. In addition, the design of the intervertebral fusion is derived from the bracing-compression effect, and traumatic fracture dislocations of the vertebral body that disrupt the corresponding ligamentous and fibrous ring tissues cannot be included as indications for surgery. Filler in the intervertebral fusion The autologous cancellous bone removed during the intervertebral decompression operation is often filled in the fusion device, and the good immunocompatibility and osteoinductive effect of the autologous bone facilitates fusion. When autologous bone is insufficient, allogeneic cancellous bone is widely used and recombinant human BMP-2 is often used to promote fusion. Many investigators believe that BMP-2 can result in a 100% fusion rate, but have also found an increase in early complications, mainly bone resorption or transient space loss. Considering the lack of difference in VAS scores and fusion rates, some investigators believe that bone resorption should be considered as a process of fusion rather than a complication. Judgment of clinical fusion It is very difficult to determine fusion after conventional metal-based interbody fusion. Because X-rays do not pass through the metal and create artifacts around the metal, the growth of trabecular connections within and around the fusion cannot be directly visualized on X-rays, making it difficult to determine whether interbody fusion has been achieved. In contrast, a homogeneous allograft fusion does not significantly obscure X-rays and has a significant advantage in terms of imaging judgment. In general, fusion is considered to have occurred when an x-ray shows a new trabecular connection between the vertebrae. At a minimum, the new trabecular junction represents functional stability between the vertebral segments, which may be provided by the bony fibrous junction or locking card within the fusion. In addition, the absence of pain and motion of the vertebral segment in the patient may also be a basis for determining bony fusion. Summary The advantages of allogeneic intervertebral fusion can be briefly summarized in the following five points: (1) the fusion structure is more in line with the normal intervertebral space morphology; (2) the elastic modulus is close to that of normal human bone; (3) it has little effect on imaging; (4) it can be completely resorbed; and (5) it has good osteogenic activity. Although homogeneous intervertebral fusions have shown good results in clinical applications, with theoretical advantages such as osteogenic activity and elastic modulus, there is still insufficient evidence to show that homogeneous intervertebral fusions have significant advantages over other materials such as PEEK; at the same time, because homogeneous intervertebral fusions have been in use for a relatively short period of time, there is a lack of long-term follow-up data to judge their long-term effects; their pathological changes during the fusion process and imaging The pathological changes and imaging manifestations during the fusion process are different from those of metal or synthetic fusion devices, which deserve in-depth study. Therefore, the optimal indications and long-term results of allogeneic intervertebral fusion need to be studied in depth in order to provide sufficient evidence for clinical decision making.