Cranial defects due to various causes are very common in clinical practice, and repair and molding of cranial defects has become a consensus among neurosurgeons. The guidelines for the treatment of craniocerebral trauma in various countries generally recommend debridement as the first choice in the second-line treatment of malignant high cranial pressure, and debridement can effectively reduce the intracranial pressure and reduce the compression of the brainstem vital centers. At present, the surgical indications for severe craniocerebral injury are becoming more standardized, and surgical treatment is still based on traditional debridement or standardized large bone flap decompression as an important method. With the promotion and application of standardized large bone flap decompression for heavy craniocerebral injury, more and more cases of large cranial defects are bound to appear in the clinic, so timely repair of cranial defects is essential. So far, the timing, indications, contraindications, repair materials and repair methods of cranial bone repair are still controversial. I. The necessity of cranial bone repair Although the early stage of decompression surgery after demineralization can achieve the purpose of reducing intracranial pressure and increase the cerebral perfusion pressure and cerebral blood flow on the decompression side; however, subsequently, due to the loss of the support of the bone flap, the role of atmospheric pressure makes the intracranial, especially on the side of the demineralization flap, cerebrospinal fluid circulatory dynamics disorders and cerebral perfusion pressure decreased, resulting in cerebral metabolic disorders caused by the potential functional damage to the brain tissues. Large cranial defects not only change the normal pressure in the cranial cavity and the circulation of intracranial blood and cerebrospinal fluid, but also break the original physiological balance in the cranium, resulting in the contents of the cranial cavity in a variable state, which can easily cause deformation of brain tissues, displacement, ventricular enlargement, and disruption of the flow of water in the brain parenchyma, which affects the production, absorption, and circulation of the cerebrospinal fluid, resulting in the formation of traumatic hydrocephalus, cerebral bulging, and other complications. It causes a series of neurological symptoms such as headache, dizziness, localized tenderness, irritability, anxiety, fear, unexplained discomfort and various mental disorders, which is called trephined syndrome. Improvement of clinical symptoms in patients with post-traumatic demineralized flap decompression by cranial repair has been reported for a long time, such as alleviation of trephined syndrome symptoms and improvement of cognitive function, etc. Dujovny et al. found that after cranial repair in patients with bifrontal demineralized flap decompression, the flow of cerebrospinal fluid was significantly improved, and the blood flow of cerebral veins was also increased to a certain extent. Animal experiments showed that cranial defects caused by decompression of the desmoid flap had significant alterations in local cerebral hemodynamics, which associated caused changes in cerebral oxygen metabolism rate and cerebral glucose metabolism rate, and further contributed to the impairment of cerebral neurological function. Winkler et al. reported that cranial bone repair improved the hemodynamic disorders of the middle cerebral artery and the internal carotid artery on the repair side, and significantly improved the cerebral blood flow reserve capacity of the cerebral blood flow that was significantly impaired by decompression of the desiccated flap; after cranial bone repair, the cortical perfusion disorders on the side of the original cranial bone defect could be restored to a near-normal level. In patients with cranial defects, more than 70% of cranial defects are found in the forehead, the brow arch contour, and the adjacent temporoparietal region, which is an important part of the face and facial features. Temporal muscle atrophy, deflation of the temporal region, and even alteration of the position of the temporomandibular joint, which affects mastication, are often seen after debridement and decompression surgery. The integrity of temporal muscle form and function depends on its innervation, blood supply, intact muscle fibers, and moderate muscle tone. Temporal muscle atrophy not only affects the patient’s appearance, but also causes physical and psychological damage to the patient. Achieving the surgical effect of reconstruction and aesthetics after human injury by means of scientific and technological innovation is an inevitable trend in the development of medical reconstruction and aesthetics.Segal et al. reported that the average blood flow rate in the patients’ cranial defect site slowed down and the pulsatility index increased, suggesting that the slowing down of the blood flow rate was related to the area of the cranial defect, and that the greater the area of defect, the lower the intracranial pressure, and the slower the cerebral blood flow rate, which caused the microcirculation of the cranium to be ischemic and anoxic. Winkler et al. studied the cerebrospinal fluid (CSF) kinetics, cerebral vascular reserve capacity and cerebral glucose metabolism of patients with cranial bone defects and found that there were different degrees of disorders in CSF kinetics, decreased cerebral vascular reserve capacity, and decreased cerebral glucose metabolism. After cranial repair, with the correction of CSF kinetic disorders, cerebral vascular reserve capacity recovery, cerebral glucose metabolism increase, the patient’s neurological symptoms can be completely disappeared or partially improved. Second, the timing of repair Cranial bone repair is not only from aesthetic considerations, but more importantly for therapeutic purposes. The role of cranial bone repair is mainly to restore the physiological integrity of the cranial cavity, and improve the psychological safety of the patient and some neurological symptoms such as headache, dizziness, nausea, etc. The timing of the surgery should be chosen for the recovery of the wound and the injured brain tissues to a better and stable state. It is usually considered that cranial repair should be performed more than 3-6 months after debridement, and for those with infection, it should be prolonged to at least 6 months after debridement. If the time is too long, the local skin scar is not easy to heal after the operation, and because the skin and dura mater or brain tissue are closely adhered to each other, it increases the difficulty of separation in the surgical operation, and it is more damaging to the skin and brain tissue. The skin flap collapses for too long, easily causing the skin flap to shrink, and the skin edge is tense after suturing, easily leading to ischemic necrosis. The indications for early cranial repair still need to be further explored, such as the effects of intracranial pressure, state of consciousness, general condition, and complications on the indications for surgery. Du Guangyong et al. reported that it is feasible to perform cranial bone repair in the ultra-early stage (4-6 weeks) after decompression of the debridement flap in heavy craniocerebral injuries; however, the wound and the damaged brain tissues have not yet recovered to a stable level during the postoperative period of 4-6 weeks, and the authors believe that repair at this time is untimely. Li Gu et al. showed that patients with early cranial repair (<2 months) had a better prognosis than those with delayed repair (>3 months). This study has some clinical guidance value, and a prospective controlled clinical study would be more convincing. With the standardized treatment of craniocerebral injuries and the popularization and application of standard traumatic large bone valve decompression, the success rate of craniocerebral injuries has been significantly improved, but complications such as cranial bone defects, brain swelling, and hydrocephalus caused by the surgery or the trauma itself are also increasing. There are many reports on traumatic hydrocephalus. When complications such as hydrocephalus and cerebral bulging occur after debridement and decompression surgery, the traditional treatment is to perform ventriculo-abdominal shunt first and then cranial repair after 3-6 months, which is easy to miss the optimal treatment period. Guo Fang et al. used simultaneous disposable cranial repair and ventriculo-abdominal shunt for the surgical treatment of patients with cranial defect combined with hydrocephalus after craniocerebral injuries, and achieved satisfactory results, which significantly reduced the patient’s consciousness and neurological dysfunction. At present, there are many reports on early cranial bone repair. In this paper, we believe that patients undergoing early cranial bone repair should exclude increased intracranial pressure, intracranial space-occupying masses, cerebral swelling and cerebrospinal fluid abnormality, and that once intracranial pressure and other contraindications to cranial bone repair are excluded, early cranial bone repair should be performed. Cranial bone repair materials should have the following conditions: (1) small tissue reaction, do not produce tissue rejection; (2) material stability, in vivo will not cause ionization reaction, and not be absorbed by the tissue; (3) light weight, strong, have a certain impact resistance; (4) plasticity, easy to form, after repair appearance is satisfactory; (5) can be permeable to X-rays, so that the postoperative patients are still able to carry out X-ray, CT, MRI and other reviews; (5) X-ray, so that the patient can still carry out X-ray, CT, (6) small thermal conductivity; (7) easy to use, simple surgery; (8) low price, convenient supply. Traditional cranial bone repair materials mainly include Plexiglas, methyl methacrylate bone cement, titanium plate, silicone rubber plate, polymer fiber reinforced material and bisacrylate microporous plasticized artificial skull. Most of these materials have the disadvantages of poor histocompatibility, susceptibility to infection and formation of flap effusion. The commonly used cranial bone repair materials in the clinic include autogenous cranial bone, plexiglass, bone cement and titanium alloy materials. Allogeneic bone (fresh fetal skull), autologous heterotopic bone (such as ilium, scapula, tibia, ribs) or homologous allogeneic bone have been used in the past. Cranial bone repair materials are divided into two categories: autogenous bone and artificial materials, with the deepening of research and the development of science and technology, more artificial materials have been used in the clinic.Dumbach et al. applied cancellous bone, hydroxyphosphate lime particles, titanium plate, and succeeded in repairing the cranial bone defects after radiation irradiation. Most of the artificial materials are difficult to replace the autologous skull in terms of molding, impact resistance, compression resistance, insulation and cold resistance. So far, the more widely used artificial material is mainly titanium mesh plate, due to the titanium alloy material is non-toxic, low inflammation and sensitization, has good biocompatibility and low biological metamorphosis, corrosion resistance and other characteristics, has been more and more widely used in clinical applications. Because titanium mesh has strong compressive properties, good tissue compatibility, after implantation into the human body, fibroblasts can grow into the micropores of the titanium mesh, so that the titanium mesh and the tissues are fused into one and there is a tendency of calcification and ossification, which makes it a more ideal artificial repair material. Although titanium mesh is better in terms of aesthetic appearance, it is expensive. Up to now, there is no material that can fully meet the conditions, in contrast, some scholars believe that autologous cranial bone is the most ideal material for repairing cranial defects. The earliest application of autologous cranial bone still occupies an important position in clinical application. Autologous cranial bone conforms to one’s own physiology, does not have immune rejection reaction, and seldom occurs infections, effusion, loosening and other common complications of artificial materials. Ordinary cryopreserved autologous cranial bone can survive after implantation, which is especially suitable for children, while the artificial material is unlikely to increase in size with the increase of the skull. Autologous cranial bone has the advantages of economy and no need for shaping, but its histocompatibility, whether the bone flap still has normal physiological characteristics after leaving the body, and whether the periosteal osteoblasts are still alive are unclear, in addition, there are also the problems of resorption and hyperplasia after bone flap transplantation that deserve further study. Cranial bone preservation Clinicians have done a lot of research on how to preserve bone flaps. There are many methods of preservation, such as autologous preservation and liquid nitrogen cryopreservation, the former exists in the patient’s pain, the latter exists in the requirements of high equipment conditions, expensive and other shortcomings. Autologous cranial bone preservation methods are divided into in vivo and in vitro, in vivo preservation methods are mainly cranial bone flap buried in the abdominal wall or thigh subcutaneous, autologous subcutaneous embedded cranial bone flap is a close to the physiological state of the preservation method, can be better preservation of the bone tissue cell activity and structure, to a certain extent, maintains the biological characteristics of the bone flap, defects are limited preservation time, more than 12 weeks, the bone flap resorption is obviously have different degree of reduction, and increased trauma and medical costs. Li Yaohua et al. used cranial bone flaps preserved in the lateral femoral and abdominal walls for early (average 61 d) replantation without any adverse effects or complications. The most common complication of autologous cranial bones preserved ex vivo is infection. In the case of autologous bone flaps, the most common complication was infection, but in the case of autologous bone flaps preserved in vitro, the most common complication was infection, and in the case of autologous bone flaps preserved in vitro, the most common complication was infection. Autologous bone flap embedding and then bone grafting is more economical and suitable for grassroots hospitals, but the problems faced are the difficulty of surgical operation, easy to bleed when peeling off the dura mater, and autolysis or hyperplasia of the bone flap. In recent years, reports about deep cryogenic freezing of autologous cranial bone have appeared continuously. The cranial bone flap preserved by deep cryopreservation maintains the activity of bone tissue cells and has the same osteoconduction effect after preservation using other methods, and the osteoconductors in the matrix of the frozen bone flap are not inactivated, and they still maintain osteoconduction ability, which can promote the fusion of grafted bone and bone in the recipient area after transplantation. Based on animal experiments, Sun Peng et al. preserved the cranial bone flap removed from patients with craniocerebral trauma and intracranial tumors under deep cryopreservation (-196 ℃), and 89 patients had no rejection reaction and infection after the implementation of cranial bone replantation, and the clinical effect was satisfactory, and it was believed that the deep cryopreservation had the following advantages: (1) no immune rejection reaction, and no postoperative complications; (2) replanted bone flap could be viable and could be transplanted with the recipient bone. (2) The implanted bone flap can survive and integrate with the surrounding bone tissue, playing the same role as the original skull; (3) It is especially suitable for children; (4) It is easy to be accepted by the patients’ psychology; (5) There is a very good protection effect on the brain tissues after the autologous cranial bone implantation, such as antimagnetism and anti-electromagnetic effect; (6) The time of the bone flap implantation is not subjected to strict limitations. However, deep cryoprocessing to preserve the cranial bone flap must have certain equipment conditions and high cost, which is difficult to carry out in primary hospitals. The use of frozen plus autoclaved autogenous bone flaps for repair has the disadvantages of increased infection and graft bone resorption, the reason for which may be related to high-temperature protein denaturation. Wei Zubin et al. used aseptic technology to save the autologous skull to repair cranial defects, the results found that the autologous bone flap back to repair and artificial material efficacy is not significantly different, and saves money. V. Repair method The repair of cranial defects caused by trauma and surgical factors, unless the autologous bone flap, it is very difficult to do with the original defects in the form of complete consistency. Cranial defects have different parts, sizes and shapes, and it is difficult to match the traditional molds and handmade products with the defective areas before and during the operation, especially the titanium plate restorations do not match the physiological curvature of the original defective areas, and the symmetry of the left and right sides after shaping is not good, and the cosmetic effect is poor. In the past, most clinicians used simple tools to process and produce titanium mesh on site, and the doctors repeatedly designed, cut and shaped the mesh before and during the operation, which led to uneven surgical results due to the operator’s experience and the influence of the production tools, which not only delayed the operation time, but also often failed to achieve symmetrical cosmetic results. Moreover, more than 70% of the patients have defects in the forehead, brow arch contour and its adjacent frontotemporal parietal region, and the cosmetic effect has a direct impact on the psychological and physiological health of the patients. The application of moldless multipoint forming technology to cranioplasty marks the entry of cranial prosthesis shaping from the manual era into the digital era. In recent years, with the application of computer and three-dimensional image reconstruction technology as well as the use of automatic molds to make titanium plates, the shaping has become more perfect and precise. Currently, there is a digital design and manufacturing technology for titanium cranial prostheses, the advantage of this technology is that the digital technology combined with CT scanning three-dimensional imaging can make the prostheses made before surgery more accurate. Xia Chengde et al. used electron beam three-dimensional CT imaging technology to prefabricate medical titanium alloy into personalized titanium implants to complete four cases of large cranial defect repair. The symmetry of the titanium mesh repair with the healthy side of the skull after repair determines the cosmetic effect of the surgery. However, the computer-aided design of cranioplasty is only based on the cranial information of the patient’s cranial CT during the surgical design, discarding the information of the soft tissues, and the implanted material designed based on the cranial information will not be able to be matched if the implanted material is put in the middle between the scalp and the temporal muscle. yang et al. Based on the cranial and temporal muscle information, studied the design and fixation methods of implant materials for patients with temporal skull defects. With the development of computer-aided design and rapid prototyping technology, personalized design and manufacturing of cranial repair materials has become possible. Zhao Wenxu et al. used personalized prefabricated medical resin and hydroxyphosphatic lime composite materials to complete 48 cases of cranial bone defect repair with satisfactory results. The use of tissue engineering technology to repair cranial defects is a new direction developed in recent years, and the rapid establishment of blood vessels in tissue-engineered bone is particularly important. Xu Songbai et al. used vascular endothelial growth factor (VEGF) transgenic tissue-engineered bone to repair rabbit cranial defects, and initially explored the application of transgenic technology in cranial tissue engineering, and concluded that the VEGF transgenic tissue-engineered bone can accelerate the bone formation in the repaired area, which is expected to provide an effective method for the clinical repair of large cranial bone defects. Sixth, cranial bone repair indications, contraindications, complications Cranial bone repair should strictly grasp the indications. At present, the nationally recognized standard is that the diameter of cranial defects is >3 cm, especially the defects in important functional areas, which can easily cause neurological dysfunction. Feng Jinzhou et al. believe that the indications for early cranial bone repair are: (1) the patient’s general condition is good, mental clarity, no pulmonary infection; (2) no intracranial hypertension, cranial defect area flap has collapsed; (3) there is no intracranial and surgical area skin infection foci; (4) cranial CT examination without the surgical area of the brain tissue is obviously edema, the midline is not obvious displacement, no hydrocephalus; (5) the cranial bone defect is > 3 cm or more. Both the defect site and defect area should be considered, as well as the patient’s physical condition. The following conditions are not suitable for cranial repair: local scalp infection, intracranial infection foci resulting in increased intracranial pressure, thin scalp in the defect area, poor general condition, severe neurological deficits, and those who can not take care of themselves. Early repair is contraindicated in patients with early intracranial infection. For small defects (<3 cm) that do not affect function or aesthetics, repair is not necessary. Especially for patients with long-term coma, vegetative survival, brain death, and postoperative malignant tumors, do not blindly repair. Contraindications to cranial bone repair should be: high intracranial pressure, intracranial occupancy, cerebral swelling, and abnormal cerebrospinal fluid. The more common complications after cranial defect repair include subcutaneous effusion, hemorrhage, infection, loose subsidence of the bone flap, loosening of the titanium nail, broken plexiglass, and exposed material. Some studies have shown that the rate of exposed cranial repair material is 0.9% to 1.7%, the infection rate is 8.1% to 14.8%, and the incidence of subdural effusion is 7.6% to 12.9%. Subdural effusion is the most common complication. The occurrence of subdural effusion is related to the residual epidural dead space, local blood seepage, cerebrospinal fluid leakage and the histocompatibility of the repair material in the operation, etc. In addition, the dura mater or fibrous connective tissue membrane on the brain surface of the early repair is incomplete or insufficiently dense, which is prone to be broken when the flap is turned up, leading to subdural effusion infection. The dura mater should be kept intact and hemostasis should be thorough when peeling off the flap during surgery, and the dura mater should be suspended by silk thread in the center of the defect if the scope of repair is large. Postoperative subcutaneous effusion can be extracted by subcutaneous puncture, and most of it can be healed after pressure dressing. Some of the subcutaneous effusions need to be pumped repeatedly, which increases the pain and mental stress of the patients, and is easy to induce infection. Li Fenqiang et al. reported that the use of indwelling negative pressure drainage after repair surgery can significantly reduce this complication, and none of their 16 patients with indwelling negative pressure drainage had subcutaneous effusion. The reason for secondary hemorrhage after cranial repair may be due to the abundance of newborn capillaries and brittleness after brain tissue injury in the defect area, and the excessive pulling of brain tissue when peeling off the flap during the operation, and suspending it too deeply without avoiding the large blood vessels. The most common complication of repairing with in vitro preserved autologous cranial bone flap is infection. In addition to strict aseptic operation during the operation, prevention of infection is very important for prevention of infection by applying gentamicin solution or iodophor immersion before the operation, and routinely applying high potency antibiotics after the operation, and at the same time, paying attention to the improvement of the patient's nutritional status. Once infection occurs, the bone flap should be removed promptly without taking any chances. In addition, considering the possibility of intracranial infection, early cranial bone repair is contraindicated in cases with open craniocerebral injury or intracranial infection after trauma. Plexiglass is easy to break, try not to use, once broken after use should be promptly removed and replaced with other materials. Titanium nail loosening is related to surgical operation, intraoperative skull defect edge stripping is not complete, titanium nail is not completely nailed into the skull is the main reason. Material exposure is due to the rupture site for the original surgical incision scar, local blood circulation is poor, friction necrosis caused by the occurrence of the exchange of treatment, given to re-suture, if still not healed then need to remove the material. Prospect In recent years, the development of bone tissue engineering for the complete repair of cranial defects provides a new method, which is mainly the application of extracellular matrix composite expansion of cultured seed cells, implanted back into the defect site, in the gradual degradation of extracellular matrix at the same time, the implanted cells continue to proliferate, to achieve the purpose of repairing cranial bone defects. At present, there is still no uniformity in the timing, indications, contraindications, repair materials, cranial preservation and repair methods for cranial bone repair. With the deepening of research and the development of science and technology, whether it is the application of autologous cranial bone or the application of artificial materials, the methods will be more reasonable, the materials will be constantly improved, the complications will be further reduced, and the appearance will be more and more beautiful, and it will be helpful to improve the symptoms of the patients and improve the quality of life.