Guided bone regeneration (GBR) technology is one of the most commonly used and effective methods for clinically solving bone defects around implants. The principle is to use a barrier membrane to isolate soft tissue from growing into the bone defect area, so that the regeneration function of bone tissue is achieved. To the fullest extent. The barrier membrane plays an important role in guiding bone regeneration and is a key factor in the success or failure of GBR technology. Magnesium alloy, as a degradable and absorbable metal material, has good biocompatibility and physical properties close to bone cortex, can promote bone formation and bone regeneration, and meets the characteristics required for barrier films in GBR. As a new type of degradable biological implant material, it has been widely studied and discussed in recent years.
Basic requirements and research progress of barrier film materials
1. Basic requirements and classification of barrier films
In the GBR procedure, the role of the barrier membrane is essential for proper bone regeneration. It prevents soft tissue from growing into the bone defect area and keeps the bone space in the defect space from regenerating. To achieve maximum bone regeneration, an ideal GBR membrane should have several characteristics. ① Biocompatibility: Biocompatibility is the most basic requirement for medical human implant materials. Except that the barrier membrane does not have immune rejection and genetic and cytotoxic reactions, its degradation products cannot interfere with bone formation; For space maintenance, cell isolation and maintenance of space, it has certain stiffness and strong anti-collapse ability to create and maintain sufficient bone regeneration space during the healing period; ③ prevent migration of epithelial cells; ④ appropriate absorption time after bone regeneration A good barrier membrane should be able to stably maintain the space for bone regeneration for at least 4-6 weeks.
Barrier films are generally divided into degradable absorbent films and non-degradable films according to the degree of material degradation. Degradable absorbent membranes generally include "polytetrafluoroethylene membrane", "reinforced polytetrafluoroethylene membrane", "titanium membrane", "microporous filter membrane" and the like. Its mechanical properties are good, and its ability to isolate and maintain space is better, but there are problems such as easy exposure of the membrane to increase the risk of osteogenesis failure due to infection, difficulty in shaping, and difficulty in fitting to the tissue, requiring secondary surgery to remove and cause secondary trauma . Bioabsorbable membranes mainly include polyester membranes and animal collagen membranes.
At present, collagen membrane has been widely used in clinical practice. It has the advantages of good tissue affinity, simple operation, no need for secondary removal, and reduced patient's pain and risk of complications. However, in clinical applications, some biofilms have problems such as poor mechanical properties, inability to maintain sufficient osteogenic space, and excessive degradation rates. Therefore, the mechanical properties, degradation rate, and duration of the membrane action of the absorbable film have become hot issues to be studied and improved.
2.Research progress of barrier film
With the increasingly widespread application of guided bone regeneration membranes in the clinic, the requirements and researches on barrier membranes are also constantly improved and updated.
① The asymmetric structure multifunctional membrane has received extensive attention from scholars in recent years. Tai et al. Prepared polyhydroxybutyrate (PHB)-biphasic integrated calcium phosphate / chitosan membrane for periodontal guided bone regeneration In a way, it not only improves the performance of the barrier membrane model, but also promotes the proliferation of osteoblasts and fibroblasts.
② Slow-release bacteriostatic biofilm is to slowly release the drug by loading antibacterial drugs into the film to inhibit the growth of bacteria and reduce inflammation. Norowski et al. Prepared genipin-crosslinked nanofiber chitosan membrane-loaded minocycline and applied it to guide the regeneration of periodontal bone tissue. In vitro antibacterial tests showed that minocycline-loaded chitosan electrophoresis The spun membrane can inhibit the growth of P. gingivalis and can significantly reduce the value of early bacteria at the GTR site.
③Composite biochemical functional membranes have received widespread attention in recent years. Loading osteogenic related growth factors onto GBR membranes and slowly releasing them can promote cell activity and bone tissue growth. Bone morphogenetic proteins (BMPs) are a subclass of transforming growth factors and form osteoblasts and chondrocytes by inducing bone mesenchymal stem cells to migrate, proliferate and differentiate. Shim et al. Used a special 3D printing technology to prepare a PCL / PLGA / β-TCP GBR membrane loaded with BMP-2 to repair rabbit skull defects. RhBMP-2 can be slowly and continuously released. After 8 weeks, the skull defects are almost completely covered with bone tissue. This growth factor-loaded polymer film exhibits good mechanical properties and osteogenesis.
Characteristics and Research Progress of Biodegradable Magnesium Alloys
1. Characteristics of magnesium and its alloys
The density of magnesium is low, which is close to that of human bone density, and the magnesium alloy is under compressive strength. Material density and elastic modulus are closer to natural bones, so they can avoid the “stress shielding” effect of implant materials to the greatest extent as medical repair materials. Magnesium, as one of the trace elements in the human body, exists extensively in the body and participates in various metabolic pathways in the body. Its chemical properties are lively, and it is easy to degrade and absorb under physiological environment. The degradation of magnesium alloy can promote the deposition of calcium. It has a fast osteogenesis rate in the early stage of osteogenesis, and its bone guiding performance is better than titanium. In addition, magnesium alloys do not interfere with CT and MRI imaging examinations after surgery. Combining the above characteristics of magnesium and magnesium alloys, magnesium alloys meet the superior mechanical properties, good biocompatibility, and absorption and degradation characteristics of biological barrier membranes, and are expected to become a new type of biomaterial for guided bone regeneration.
2.Research progress of magnesium alloy as medical implant material
Magnesium alloys have been widely studied as orthopedic fixation materials. The mechanical strength of traditional orthopedic fixation materials has a large difference with the elastic modulus of natural bone, which is prone to stress breakage, resulting in slow healing of bone. During the process of material wear and degradation, toxic ions or substances may be released to cause damage to surrounding tissues, and often require secondary surgery to remove them after fixation, causing mental pain and economic burden for patients. Materials with natural bone mechanical strength, degradability and no harm to human tissue cells replace traditional orthopedic fixation materials. In view of the good biological properties and mechanical properties of magnesium alloys, many scholars at home and abroad have applied them to medical implant materials in recent years. Extensive research has been conducted on its biocompatibility, cytotoxicity, and degradation ability, and many scholars have applied it in clinical practice.
(1) Osteogenic properties of magnesium alloy and different coating surfaces
Pan Feng et al. Extracted BMSCs from New Zealand white-eared rabbits and induced them into osteoblasts, and co-cultured them with Mg-Mn-Zn alloys confirmed the good biocompatibility and good osteoinduction of magnesium alloys Human co-culture of magnesium alloy with rat precursor osteoblasts has shown good proliferation characteristics and biocompatibility. Magnesium ion is one of its main degradation products. Mg2 + can effectively promote the differentiation of stromal cells to osteoblasts, and has a certain effect on promoting calcium salt deposition.
Foreign scholars have found that the increase in magnesium ion concentration can promote the proliferation of bone marrow mesenchymal cells and enhance the expression of osteogenic genes, cell matrix formation and mineral deposition. Due to the rapid degradation of magnesium alloys, in recent years, in order to better improve its performance and slow down its degradation, researchers have conducted a series of surface modification studies to form different coatings on its surface to promote its formation. Bone properties and improve its degradation rate. Weilin Yu et al. conducted an in vitro study to establish a rabbit bone and ankle defect model, and implanted a fluorine-coated AZ31 magnesium alloy porous scaffold to evaluate the degradation and bone volume changes of the scaffold. It was found that the FA31 scaffold enhanced the magnesium alloy's corrosion resistance and It has better biocompatibility and can induce more new bone formation. MgF2-coated magnesium alloy scaffolds can enhance osteogenic differentiation and attachment of rat bone marrow stromal cells (rBMSCs).
Zhang Tao and others co-cultured the calcium-phosphorus-coated and fluorine-coated magnesium alloy with osteoblasts, skeletal muscle cells, and human bone marrow mesenchymal stem cells. The adhesion and proliferation rates of the above cells in the calcium-phosphorus-coated magnesium alloy group were all Compared with the pure magnesium alloy group, the calcium-phosphorus coated magnesium alloy can promote the expression of COLI, ALP, and OC genes, while the uncoated magnesium alloy inhibits the expression of ALP and promotes the expression of the gene OPN. Subsequent in vivo experiments confirmed that new bone formation was seen at the interface of the calcium-phosphorus-coated magnesium alloy metal and bone tissue after 8 weeks, the trabecular bones were closely packed and regular, and no significant degradation was observed at the edges of the coated magnesium alloy Traces, the calcium-phosphorus coating can delay the degradation of magnesium alloys and promote bone formation. This indicates that the calcium-phosphorus coating improves the biological properties and osteogenesis of magnesium alloys.
Some scholars abroad also believe that calcium-phosphorus-coated magnesium alloys have higher biocompatibility than pure magnesium alloys, can delay the degradation time of magnesium alloys, and can promote the formation of new bones to facilitate the fixation and implantation of implants. Healing of damaged bones. Hydroxyapatite has good compatibility with human bone, so it is applied to magnesium alloy coatings to improve the cell compatibility and bone formation of Mg alloys. Li and others used electrophoretic deposition to prepare the hydroxyl groups on the surface of magnesium alloy AZ31B. Apatite (HA) coating, which greatly improved the material's corrosion resistance and biocompatibility, and confirmed that the HA-coated magnesium alloy can promote the deposition of calcium salts around the implant and induce bone-like apatite Superior performance of stone. W scholars used a micro-arc oxidation method to implant the oxide-coated magnesium alloy stent into the prepared rabbit femoral patella defect. New bone was observed around the MAO-coated magnesium alloy 3 months after implantation. Formation and direct contact with new bone, compared with the control group, there is more bone formation. In vitro experiments confirmed that the MAO coating treatment can maintain the mechanical strength of the magnesium alloy for a period of time after implantation, providing bone healing appropriate time.
The Mg-Zr-Sr alloy prepared by Dolly et al., Which can be coated with Col-I, can significantly improve its osteoinductive activity in vitro and in vivo, showing faster new bone formation and higher mineral deposits. These different surface coating methods not only improve their biocompatibility, but also improve the corrosion resistance of magnesium alloys and reduce the degradation rate. The combined application of bone graft material and magnesium alloy can enhance its osteogenesis effect. Mineralized collagen is one of the bone graft materials commonly used in the oral cavity. Qing et al. Prepared a mineralized collagen / Mg-Ca alloy composite scaffold material to Improve the mechanical properties of collagen. The researchers implanted this composite scaffold material into the canine extraction socket to evaluate its osteogenesis and effect. CT, X-ray and other tests show that the magnesium alloy composite scaffold material can significantly promote bone regeneration than the mineralized collagen alone, effectively reduce the absorption of alveolar ridges, and preserve the bone mass at the extraction site.
In addition, magnesium alloys not only have superior osteogenic properties, but also have a good positive effect on the healing of soft tissues. The ratio of type Ⅰ collagen to type Ⅲ collagen determines the strength and mechanical stability of connective tissue to some extent, and is considered to be related to the occurrence of wound anastomosis complications. Collagen degradation after wound anastomosis is often associated with matrix metalloproteinases (MMP-1, MMP-13). (Because MMP-1 and MMP-13 are the main collagenases that cut collagen types Ⅰ and Ⅲ, they help the cleavage of the triple helix structure, which triggers the degradation of collagen.) The activity of the enzyme directly determines the type of collagen Ⅰ and Ⅲ. Synthesis and deposition rate. Wang et al. Studied the effect of magnesium alloys on soft tissue and collagen formation, experimentally established a rat cecal incision model in the abdomen, and implanted magnesium alloy nails and titanium alloy nails into the repair incision. The experiments confirmed that magnesium alloys can enhance type Ⅰ and Ⅲ collagen. The expression of MMP-1 and MMP-13 inhibited the expression of matrix metalloproteinases MMP-1 and MMP-13, indicating that Mg-6Zn alloy can stimulate the synthesis and accumulation of cellular matrix (ECM) under the same conditions, and promote wound anastomosis and healing.
(2) Antibacterial properties of magnesium alloys
Infection is one of the common complications after implantation. Once the implant is infected, bacteria will adhere and colonize around the surface and the interface between the implant material and the bone, and the colonization of the bacteria will cause the infection. continue living. Research on the antibacterial properties of magnesium alloys has also become a research hotspot for scholars. Some studies have shown that the antibacterial properties of implants play an important role in determining the success of implantation results. Zinc ions have excellent antibacterial capabilities. Researchers have designed a new quaternary magnesium-calcium-strontium-zinc-zinc alloy material and found that it has obvious antibacterial properties and that the level of this performance is positively related to the zinc content. The foundation is laid for degrading antibacterial implant materials.
Preparation of magnesium hydroxide film on AZ31 magnesium alloy substrate and multilayer film formed by gentamicin sulfate (GS) and sodium polytetrastyrene (PSS) layer by layer assembly, showing superior antibacterial performance, layer by layer assembly Multilayer film can effectively inhibit the growth of Staphylococcus aureus in vitro. After oral implantation of magnesium alloy, the degradation products will increase the local pH value to a certain extent, reduce the amount of Pg, Fn, Pi, and Aa in the local plaque implantation, and achieve the antibacterial effect. It is a magnesium alloy used for preventive planting. Periarthritis and periodontitis laid the foundation. In vitro experiments conducted by Brooks et al. Found that compared with commercial pure titanium, the number of bacterial colonies and the size of biofilms on the surface of magnesium alloy AZ91 were significantly reduced, confirming that magnesium alloy can reduce the adhesion of A. baumannii to a certain extent. However, in vivo experiments, pure magnesium implants did not appear to be sufficient to inhibit bacterial colonization and even prolong the existence of bacterial biofilms.
Therefore, the antibacterial properties of magnesium and its alloys need to be continuously improved through a series of technologies and the antibacterial effect in the body must be clarified. Because of the advantages of magnesium alloys in terms of superior physical properties and biocompatibility, we envision whether magnesium alloys can be used as such a barrier film material, while possessing the properties of maintaining space and a certain stiffness, and Absorbable degradation promotes bone and soft tissue regeneration. In the past 13 years, some scholars have used magnesium alloy as a guide for bone tissue regeneration membrane, and combined with tissue engineering to perform bone vertical incremental repair of severely absorbed canine mandibular alveolar bone and observe its osteogenic effect. The results showed that the initial osteogenesis rate of the magnesium alloy film group was significantly better than that of the titanium alloy film combination without the cover film group.
Bone formation was active around the magnesium alloy material, and the bone density and trabecular volume analysis were not significantly different from those of the titanium alloy film. However, due to degradation and gas generation in the magnesium alloy group, the bone formation volume was smaller than that in the titanium alloy group, and the surface height was irregular. Therefore, how to control the degradation and gas generation of magnesium alloys has become a difficult point that we need to overcome, and further research and practice are needed to provide a theoretical basis for its future clinical application as a guide for bone regeneration membranes.
Problems and Outlook
Magnesium alloy film has superior physical properties and good bone guiding and osteoinductive properties. However, due to degradation and gas generation, the osteogenic volume is affected. The research of magnesium alloy materials needs to slow down the degradation rate and how to make the degradation rate of magnesium alloy match the speed of bone formation, so it needs to be further explored to provide a stable osteogenic space. The application of different coating modification methods to enhance the biocompatibility of the magnesium alloy barrier film while maintaining its good mechanical support, and how to further promote soft tissue healing and improve antibacterial capabilities are worth further research, so as to improve the magnesium alloy Guiding the Application Potential of Bone Regeneration Barrier Membrane.