CN113171224B - An implanted bandage for promoting bone injury repair and preparation method thereof - Google Patents

Abstract

The invention discloses an implanted bandage material for promoting bone injury repair and a preparation method thereof. The bandage is composed of a porous grid sheet-shaped object and organic-inorganic composite superfine fiber porous film covering the surfaces of two sides of the porous grid sheet-shaped object, the lower layer is a superfine fiber porous network containing biological glass particles, the middle layer is a polymer porous grid, and the upper layer is a superfine fiber porous network containing inorganic mineral particles; inorganic matters in the superfine fibers on the surfaces of the two sides respectively consist of bioglass particles for inhibiting inflammation, resisting infection and promoting the regeneration and repair of soft tissues and inorganic mineral particles for inhibiting inflammation and promoting the regeneration and repair of bones, and the bandage is prepared by a three-dimensional printing and electrostatic spinning process. The method of the invention has convenient operation, has obvious inhibiting effect on inflammation in soft and hard tissues such as muscles, periosteum, bones and the like of various fractures or bone defects, promotes the rapid healing and repair of the soft and hard tissues, has adjustable degradation rate of the implanted bandage and has obvious bacteriostatic action on common pathogenic bacteria and fungi.

Description

A kind of implanted bandage for promoting bone injury repair and preparation method

technical field

The invention belongs to an implanted bandage in the field of biomedical implant materials and a preparation method, and particularly relates to an implanted bandage material and a preparation method for promoting the synergistic regeneration and repair of soft and hard tissues of bone injury.

Background technique

Bone injuries usually include fractures and bone defects, which may also be referred to as bone trauma and bone loss. In my country, more than 100,000 people die every year from fractures or bone trauma caused by accidents such as traffic accidents, falls, smashes, and falls. Defects or bone loss, especially in the middle-aged and elderly people at the site of bone damage caused by various chronic diseases and inflammation, have poor blood supply and slow recovery, resulting in delayed fracture union, malunion or even nonunion (nonunion). Although there is a broad consensus and experience in the clinical practice of conventional fracture treatment, a large number of limb bone fractures with severe muscle and periosteum damage, and hip fractures in the elderly require a second operation or even become disabled and have a high risk of death. The incidence of delayed union of fractures is as high as 6% to 10%, which is much higher than the clinical incidence of artificial prosthesis infection. At the same time, the regeneration and reconstruction of large segmental bone defects in the limbs requires higher blood supply recovery efficiency. Bone trauma with severe periosteal damage requires related treatment methods to promote periosteal regeneration and provide seed stem cells and blood supply for bone trauma. A major question worthy of in-depth study.

At present, the commonly used fracture care and bone trauma repair include external support belts, metal stents or implanted steel plates, intramedullary nails, artificial bone, autologous bone, etc., and anti-infective and anti-inflammatory drugs, and osteoporosis drugs are used. , Nutrients and Chinese herbal medicines to promote bone damage repair are used as adjuvant therapy in the perioperative period. For patients with severe periosteal damage, blood supply problems can also be solved through periosteal transplantation. However, the adverse effects of muscle and periosteal injury and the resulting soft tissue inflammation on fracture healing are often overlooked in these conventional bone injury repair treatments. In recent years, people have paid more attention to the basic research and development of biomimetic periosteum. A large number of scaffolds based on hydrogels, electrospun fiber membranes or acellular extracellular matrix have been used as scaffolds for periosteal tissue engineering. Grow on these biomimetic matrix materials and promote the functional features of vascularization and osteogenesis. Unfortunately, people still ignore the role and impact of potential problems such as inflammatory responses in soft and hard tissues and bacterial infections on delayed healing and repair of bone injuries, especially in the middle-aged and elderly, such as osteoporosis, diabetes, and femoral head necrosis. Disease and markedly reduced metabolic capacity adversely affect fracture healing efficiency. Therefore, it is urgent to research and develop new materials for the treatment of fractures and bone trauma with severely damaged periosteum and severely damaged muscles, or for limb fractures and bone defects with extremely limited muscle coverage.

Accordingly, new materials to promote bone injury repair must require simultaneous intervention and regulation of the soft and hard tissue wounds at the injury site, especially to solve three problems:

First, the persistent inflammatory response caused by muscle tissue trauma may adversely affect the internal repair of bone injury, and the need for timely healing of muscle trauma and infection prevention and control.

Second, the blood supply in the bone defect is seriously affected after the periosteum is damaged. The reconstruction and repair process of the periosteum itself cannot provide positive support in terms of nutrient supply for the repair of bone damage, and the lack of periosteum-derived stem cells will also jeopardize the improvement of the healing efficiency of bone damage.

Third, the active stimulation of rapid repair of pathological skeletal bone injury requires external supply, and to avoid chronic inflammation of soft tissue trauma from participating in the cellular and molecular biological processes at the broken end of the bone defect, which is not conducive to angiogenesis and cartilage callus formation.

Therefore, the intervention and treatment of this type of bone injury cannot only rely on oral, intravenous injection or biomimetic tissue-engineered periosteal implantation. It is necessary to establish a matrix based on soft and hard tissue infection, inflammation and new tissue to facilitate the growth and synergistic repair of the three The efficient mediation of multifunctional implants with synergistic aspects of each aspect can solve many clinical problems such as delayed healing and malunion of bone injuries.

In recent years, studies have found that some amorphous glass materials constructed of inorganic oxides or inorganic ions have a significant inhibitory or even killing effect on various bacteria, can regulate the activity of immune cells, mediate the development of inflammatory responses towards tissue repair, and can also Promote vascularization and regeneration and healing of soft tissues such as skin and periosteum. For example, a large number of studies have found that copper and zinc ions can inhibit and kill harmful bacteria in wounds, and have broad-spectrum bactericidal properties. At the same time, zinc, magnesium and other ions can also regulate the expression of inflammatory factors in immune cells, and have anti-inflammatory effects; and copper and magnesium ions can regulate the activity of vascular endothelial cells and the high expression of vascularization growth factors, thus showing excellent promotion of vascularization. Effect. Secondly, it has also been confirmed that some degradable calcium phosphate and calcium (magnesium) silicate inorganic compound materials can promote bone tissue regeneration and repair, and have anti-inflammatory and bactericidal properties after doping with inorganic ions such as zinc, magnesium and copper. Feature. Therefore, it is feasible to solve difficult clinical problems by constructing fracture treatment materials with anti-inflammatory, anti-infection and promotion of synchronous regeneration and repair of soft and hard tissues.

According to the existing technical research, there is an urgent need to create research on chemical composition, micro-nano structure, physical and chemical properties, mechanical properties (involving the maneuverability of surgical implantation and structural stability for a long period of time after surgery) and biological effects. It is a multifunctional implant bandage material that can effectively heal and repair various bone injuries in the human body in clinical practice. Such materials not only have compatibility with human cells at the cellular and molecular levels, but also actively regulate vascularization, muscle, Soft and hard tissues such as periosteum and bones are regenerated, and the microstructure of the material is conducive to nutrient transmission and tissue regeneration, repair, adhesion and growth. Therefore, only through innovative design and optimized construction in terms of chemical composition, microstructure and function can it become a new generation of implanted bandage materials that promote bone injury repair, and solve the risk of delayed healing and non-repair of a large number of clinical bone injuries.

According to the existing patent technology, research literature reports and clinical applications, it is urgent to design an implanted bandage that can promote the repair of bone injury. The functions and efficacy of such an implanted bandage that promotes the repair of bone injury include:

1) Even if the wound surface is not cleaned thoroughly or the bacteria of other tissues and organs migrate to the wound surface, it can remain uninfected;

2) It has good surgical plasticity and operability, and has significant multifunctional synergistic performance in the early stage of bone injury healing;

3) It can quickly and effectively control infection, inhibit the development of chronic inflammation, and promote the development of inflammatory response in the direction of tissue regeneration;

4) Promote vascularization;

5) Stimulating osteogenic activity on broken ends of bone injury;

6) It can become a matrix (scaffold) for periosteal regeneration and promote periosteal regeneration and reconstruction;

7) Economical price, easy to widely circulate and equip;

8) No side effects, no new damage to wound tissue, excellent biocompatibility, and basically complete degradation and absorption when bone damage repair and callus reconstruction are completed.

SUMMARY OF THE INVENTION

In order to solve the missing technical gap in the background technology, the present invention proposes an implanted bandage material and a preparation method for promoting the repair of bone injury. The film-covered bandage-type material is used to promote bone injury repair and prevent and control various side effects, making up for the serious defects and deficiencies of the prior art.

In the present invention, two multifunctional inorganic ultrafine particle materials are integrated into two surfaces of a two-dimensional porous grid, and a variety of active ion compositions are released through their degradation to solve the functional requirements of soft and hard tissue healing in bone injury wounds.

After the implanted bandage material for promoting the repair of bone damage of the present invention is in contact with the wound surface, the ultrafine particles in the fibrous network on the contact surfaces of the bone defect and the muscle will release the multi-component inorganic ion composition and cause local anti-inflammatory, anti-infection and promotion. It has excellent vascularization and tissue regeneration and repair effects, and has excellent healing and repair effects on various types of severe bone injuries.

The implanted bandage material for promoting bone injury repair of the invention not only solves various functions such as rapid anti-inflammatory, high-efficiency bacteriostasis, promotion of muscle and periosteum regeneration, and healing and repair of fractured ends, but also solves the problems of simple operability, complete degradation and absorption, etc. , so as to achieve the ideal standard of promoting bone injury repair, and provide an excellent new implant bandage material for promoting bone injury repair for solving clinical problems.

The technical scheme adopted in the present invention is:

1. An implanted bandage material for promoting bone injury repair:

The implanted bandage material for promoting bone damage repair is a multi-layered porous network structure, the lower layer is mainly composed of a microfiber porous network containing biological glass particles, the middle layer is mainly composed of polymer porous meshes, and the upper layer is mainly composed of inorganic materials. The mineral particles are composed of a microfiber porous network, and the pore channels of the fiber porous network and the polymer porous network are respectively 0.30-1200 μm and 200-1800 μm.

The above-mentioned ultrafine refers to fibers with a diameter of nanometer to tens of micrometers.

The particle size of the biological glass particles is 0.04-8 μm, and the particle size of the inorganic mineral particles is 0.02-20 μm.

The superfine fiber refers to collagen, chitosan, alginic acid, hyaluronic acid, gelatin, polyethylene glycol, polylactic acid, carboxymethyl chitosan, polyallyl ammonium hydrochloride, polyethylene An organic substance or a composite of any of them among imine, polyvinylamine, polyvinylpyridine and polylysine, and the diameter of the ultrafine fiber is 0.10-20 μm;

The polymer porous mesh refers to polylactic acid, polylactic acid-co-glycolic acid copolymer, polycaprolactone, poly-L-lactide-caprolactone, sodium alginate, hyaluronic acid, chondroitin sulfate, poly An organic substance or a complex between any of them in methacrylic acid, dextran sulfate, sodium carboxymethyl cellulose, cellulose, polyacrylic acid, polystyrene sulfonic acid, polyvinyl sulfonic acid and polyvinyl phosphoric acid, The cross-sectional shape of the mesh skeleton fiber is not strictly limited, and the cross-sectional dimension is 100-1200 μm.

The bioglass particles are mesoporous structure skeletons prepared by adding mesoporous structure directing agents using silicon oxides and boron oxides by a sol-gel method, and multi-component oxides are added to the mesoporous structure skeletons. The mesoporous structure skeleton is formed by hybridization of all glassy or partial glassy substances, and the main components are SiO ₂ -B ₂ O ₃ -CaO-MgO.

The bioglass particles also contain one or more of CuO, ZnO, Na ₂ O, K ₂ O, and P ₂ O ₅ .

The molar fraction of each component in the bioglass particles is:

24～60 parts of SiO ₂

B ₂ O ₃ 4～30 parts

CaO 12～36 parts

1 to 12 parts of MgO

CuO 0.4 to 8 parts

0～8 parts of ZnO

Na ₂ O 0～8 parts

K ₂ O 0 to 12 parts

P ₂ O ₅ 0-16 parts.

The main components of the inorganic mineral particles are calcium phosphate, calcium silicate, calcium magnesium silicate, calcium-zinc silicate, magnesium silicate, magnesium phosphate, and zinc phosphate substances.

The inorganic mineral particles also contain one or more doping ions among Cu ²⁺ , Zn ²⁺ , Sr ²⁺ and Na ⁺ ions.

The molar fraction of each inorganic metal ion and acid ion in the inorganic mineral particles is:

1～54 parts of SiO ₃ ^2- /PO ₄ ^3-

Ca ²⁺ 1～60 servings

Mg ²⁺ 0～52 parts

0～20 parts of Zn ²⁺

Cu ²⁺ 0.6～6 servings

Sr ²⁺ 0～12 parts

Na ⁺ 0～8 servings

The rest is crystal water.

The above-mentioned SiO ₃ ^2- /PO ₄ ^3- represents one or a mixture of SiO ₃ ^2- and PO ₄ ^3- .

The present invention adopts wet chemical synthesis, sol-gel method and high temperature calcination to prepare calcium phosphate, calcium silicate, calcium magnesium silicate, calcium-zinc silicate, magnesium silicate, magnesium phosphate, zinc Phosphate substances are the main minerals, partially crystalline and fully crystalline substances doped with magnesium, zinc, copper, strontium, and sodium by heterogeneous ions.

The calcium phosphate in the inorganic mineral particles is one or more of hydroxyapatite, calcium phosphate anhydrous, calcium hydrogen phosphate dihydrate, tetracalcium phosphate, octacalcium phosphate, and tricalcium phosphate.

The calcium silicates and calcium magnesium silicates in the inorganic mineral particles are one or more of wollastonite, tobermorite, kaffirite, kaffirite, and diopside.

The calcium-zinc silicate is kesterite.

The magnesium silicate and magnesium phosphate are magnesium silicate and magnesium phosphate.

2. A preparation method of an implanted bandage material for promoting bone injury repair, comprising the following steps:

1) Add the bio-glass particles to the organic solution and stir evenly. The mass ratio of the bio-glass particles to the organic substances in the solution is 1: (2-80), and the organic-inorganic composite with the ultra-fine particle concentration of 1-100 mg/ml is prepared. Then transfer to the liquid reservoir for electrospinning, set the spinning distance to 5-18 cm, and perform electrospinning at a speed of 0.10-0.8 ml/hour under the spinning voltage of 4-20 kV, and then collect A microfiber porous film with a thickness of 10 to 400 microns on the receiving carrier of the liquid reservoir;

2) The organic matter used for preparing the polymer porous grid is directly placed in the material container of the three-dimensional printer, and the polymer of the organic matter is heated and softened and extruded out of the printing nozzle, and the microfiber porous film formed in step 1) is used as The matrix is 3D printed polymer porous mesh on the upper surface;

3) Add the inorganic mineral particles to the organic solution and stir evenly. The mass ratio of the inorganic mineral particles to the organic matter in the solution is 1:(2～80), and the compound solution with the ultrafine particle concentration of 1～100mg/ml is prepared. Then electrospin the composite solution, deposit the ultrafine fibers on the upper surface of the polymer porous grid prepared in step 2), the spinning distance is 4-15 cm, the spinning voltage is 4-20 kV, and the spinning speed is 0.10- 1.0 ml/hour to form an implanted bandage material with a thickness of 10-800 microns.

The organic solution is collagen, chitosan, alginic acid, hyaluronic acid, gelatin, polyethylene glycol, polylactic acid, carboxymethyl chitosan, polyallylammonium hydrochloride, polyethyleneimine , polyvinylamine, polyvinylpyridine and polylysine, an organic compound or a solution of any complex between them.

The receiving carrier is porous metal aluminum foil or copper foil, the pores are any one of triangle, quadrangle, hexagon, circle and honeycomb or a combination of the two, and the pore size is 0.3-2000 microns.

The pore shape of the porous grid is not strictly limited, and the pore shape can be one of a circle, a quadrilateral, a hexagon, an ellipse, or a combination of any two, but the pore size of the grid is 50. ~850 microns, and the thickness of the polymer porous grid is 200 to 1200 microns.

The application of the implanted bandage material for promoting bone injury repair in autonomous anti-inflammatory, autonomous antibacterial and promoting efficient healing or regeneration of muscle tissue, periosteum tissue and bone tissue.

The implanted bandage material for promoting bone injury repair of the present invention is used in the field of promoting the healing and repair of various types of periosteum and severe muscle injury fractures or bone defects.

The application of the implanted bandage material for promoting bone injury repair of the present invention is characterized in that the bandage is constructed in multiple layers, and the polymer porous grid is used as a carrier to solve the problem of mechanical support, and the ultra-fine fiber porous network containing biological glass particles and The microfiber porous network containing inorganic mineral particles modifies the two surfaces of the polymer porous grid respectively, so as to ensure that the side in contact with the muscle and the side in contact with the bone wound can be controlled by different chemical components. Therefore, it can take into account the synergistic intervention of soft and hard tissues at the injury site, effectively regulate the inflammatory response and prevent infection, and synergistically promote the regeneration and repair of soft and hard tissues.

The application of the implanted bandage material for promoting bone injury repair of the present invention solves the long-term adverse effects of persistent inflammation of soft tissue under severe damage to periosteum and muscle on the early healing of injury, and the slow self-repair of soft tissue causes poor blood supply at the site of bone injury , causing serious problems such as delayed healing, non-repair and deformity repair of bone injury, and also solved the problem of delayed healing and repair of bone injury caused by incomplete debridement or secondary bacterial infection at the bone injury site.

The implanted bandage material for promoting bone damage repair of the present invention has special inorganic oxides in the bioglass particles, which is beneficial to maintain and improve its biocompatibility, anti-inflammatory, antibacterial, and promote muscle and periosteum regeneration and repair.

The implanted bandage material for promoting bone injury repair of the present invention is doped with inorganic ions in inorganic mineral particles, which is beneficial to maintain and improve its biocompatibility, control inflammatory response, antibacterial and promote bone injury healing and repair.

The implanted bandage material for promoting bone injury repair according to the present invention has secondary modification on the surface, which is beneficial to organic and inorganic molecules or ions that improve the efficiency of anti-inflammatory, anti-infection and tissue healing.

The implanted bandage material for promoting bone injury repair according to the present invention has no strict limitation on the structure of the mesopore structure of the bioglass particles, and can be a square hole, a hexagonal hole or a composite structure of the two.

The organic matter of the superfine fiber porous membrane of the present invention refers to collagen, chitosan, alginic acid, hyaluronic acid, gelatin, polyethylene glycol, polylactic acid, carboxymethyl chitosan, polyallyl ammonium It is composed of an organic compound or any combination of them among hydrochloride, polyethyleneimine, polyvinylamine, polyvinylpyridine and polylysine.

The polymer porous grid of the present invention is made of polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone, poly-L-lactide-caprolactone, sodium alginate, hyaluronic acid, chondroitin sulfate , polymethacrylic acid, dextran sulfate, sodium carboxymethyl cellulose, cellulose, polyacrylic acid, polystyrene sulfonic acid, polyvinyl sulfonic acid and polyvinyl phosphoric acid. composition.

The implanted bandage material for promoting bone injury repair according to the present invention has no strict restrictions on the morphology of the ultra-fine fiber porous network on the two surfaces of the two-dimensional sheet-like polymer porous grid in the bandage, and can also be a porous film, a porous sponge , in order to facilitate the coverage of soft and hard tissue wounds at the site of bone injury and the needs of wound healing.

The implanted bandage material for promoting the repair of bone injury according to the present invention can be prepared by various three-dimensional printing processes for the composite preparation process of the multi-layered porous structure, or can be prepared by a phase separation method, a freeze-drying method, or a micro-particle pore forming method. The three-layer composite materials formed belong to the category of implanted bandage materials for promoting bone injury repair according to the present invention.

The implanted bandage material for promoting the repair of bone damage according to the present invention has no strict limitation on the scope of application, and can be used for promoting the synergistic repair of damaged soft and hard tissues in the healing and repairing of any bone in the human body, and can also For periodontal bone healing and avoiding soft tissue ingrowth and isolation.

It can be seen from the above that the bandage of the present invention is composed of a porous mesh sheet and the surfaces on both sides thereof are covered by an organic-inorganic composite ultrafine fiber porous film. It is composed of bioglass particles that promote soft tissue regeneration and repair and inorganic mineral particles that inhibit inflammation and promote bone regeneration and repair. The bandage is prepared by three-dimensional printing and electrospinning technology, which is easy to operate and is suitable for muscles, periosteum, bones, etc. of various fractures or bone defects. The inflammation in the soft and hard tissues has a significant inhibitory effect, and it promotes the rapid healing and repair of the soft and hard tissues. The degradation rate of the implantable bandage can be adjusted, and it has a significant bacteriostatic effect on common pathogens and fungi.

The beneficial effects that the present invention has are embodied in:

1) In terms of composition, the mesoporous bioglass particles and fully or partially crystalline inorganic mineral particles synthesized by conventional technology will slowly degrade in contact with tissue fluid, and the released ion composition is the physiological metabolism of human body or tissue. Minerals necessary for regeneration and repair, there are no ion components that seriously affect the cytocompatibility of soft and hard tissue regeneration, and some ions also significantly exhibit anti-inflammatory, anti-harmful bacteria activity and/or promote vascularization and other effects , so it can prevent various risks and play the role of tissue repair stimulating activity.

2) In terms of (micro) structure, two organic-inorganic composite microfiber porous membranes cover the two surfaces of the polymer porous grid, and their porosity not only partially blocks the inflammatory response from soft tissue injury and even the involvement of soft tissue. In addition, the ultra-fine fiber micro-nano structure on the surface of the bandage is also extremely conducive to the adhesion and growth of periosteal regeneration-related stem cells, providing a good scaffold for accelerating periosteal regeneration and reconstruction.

3) In terms of biological effects, it is a biodegradable bioglass particle based on the synergistic construction of human minerals and trace elements with the synergistic biological effect of highly effective anti-inflammatory, anti-infection and promoting the healing of soft and hard tissues. and inorganic mineral particles, when loaded by organic fibers and contact with muscle and bone wounds, the multifunctional ions released by their gradual degradation can quickly reduce inflammation and antibacterial, create good conditions for wound tissue regeneration and healing, and realize muscle and periosteum in bone wounds. Both the bone and the bone are efficiently healed or repaired, and the problems of delayed healing, malunion or even non-repair in cases of severe bone injury (fracture, bone defect) are simultaneously solved.

4) In terms of preparation process and clinical application operability, 3D printing, electrospinning and other processes can be used to prepare sheet-like polymer porous grids and organic-inorganic composite ultrafine fiber network films, and the three-layer structure can be used to superimpose one by one. , thereby constructing an implanted bandage material that promotes the repair of bone damage. At the same time, this type of sheet-like porous bandage can be directly wrapped around and covered on the surface of bone injury, and then wrapped with damaged muscle tissue without excessive bandaging, effectively solving the problems of nutrient transfer in the contact interface area between soft and hard tissues and tissue self-healing and repairing.

Therefore, the significant features of this implanted bandage material for bone-injury repair are: the preparation process of the material is simple, the material can be tailored and accurately covered according to the bone injury site; it can efficiently reduce inflammation, effectively prevent and control wound surface bacterial infection, and promote soft, Hard tissue heals, avoids problems such as infection and delayed healing of bone injury wounds, greatly improves the treatment strategy for bone injury healing and repair, and avoids conventional internal and external fixation and nutritional intake.

Description of drawings

Fig. 1 is a flow chart of the preparation process of implanted bandage material.

Fig. 2 is the scanning diagram of the microfiber porous network implanted in the bandage material, wherein A in Fig. 2 and B in Fig. 2 are the microfiber membranes containing bioglass particles, and C in Fig. Microfiber membrane of mineral particles, D in Figure 2 is a microfiber membrane containing inorganic mineral particles on a porous grid skeleton.

Figure 3 is a transmission electron microscope image of the microfiber porous network implanted in the bandage material, wherein A in Figure 3 is a microfiber membrane containing bioglass particles, and B in Figure 3 is a microfiber membrane containing inorganic mineral particles.

Figure 4 is a graph showing the results of the inhibition of Staphylococcus aureus by the bioglass component implanted in the bandage material.

Fig. 5 is a graph showing the tissue healing effect of implanted bandage material on a combined injury model of periosteum-bone trauma.

Detailed ways

The content of the present invention is further clarified below in conjunction with the examples, but these examples do not limit the scope of the present invention, and all technologies and materials prepared based on the above-mentioned content of the present invention all belong to the protection scope of the present invention. The purity of the reagents used in the examples is not lower than the purity index of the analytical reagents.

Embodiments of the present invention are as follows:

Example 1: 0.04-8 μm, the particle size of the inorganic mineral particles is 0.02-40 μm.

1) Mesoporous bioglass nanopowder (chemical composition: 28CaO _- 42SiO2-12B2O3-4P2O5-6MgO _{- 1CuO -} 2ZnO _- 4Na2O _- 1K2) with a particle size of _0.15-0.85μm O) Add to the hyaluronic acid-gelatin composite aqueous solution with a mass ratio of 1:9 and stir evenly, the mass ratio of bioglass to organic matter is 1:20, and prepare an organic-inorganic composite with a bioglass concentration of 50 mg/ml The solution was then transferred to the electrospinning reservoir, the spinning distance was set to 15 cm, the spinning voltage was 16 kV, and electrospinning was carried out at a speed of 0.4 ml/hour, and then the porous copper foil carrier was collected on a porous copper foil carrier with a thickness of 200. Micron-level microfiber porous membrane;

2) The organic substance used for preparing the poly-L-lactide-caprolactone porous mesh is directly placed in the material container of the three-dimensional printer, and the polymer is softened by heating and extruded out of the printing nozzle, and the result is formed in step 1). The microfiber porous film is used as the matrix for three-dimensional printing of polymer porous grids, the size of the square pores of the porous grids is 650 microns, and the thickness of the printed porous grids is 200-1200 microns;

3) Inorganic mineral particles with a particle size of 0.02-0.08 μm (the mole percentages of inorganic ions and acid ions contained are SiO _{3 2-45%, PO 4} ^{3- 5} %, Ca ²⁺ 40%, Mg ²⁺ 4%, Zn ²⁺ 2%, Cu ²⁺ 0.6%, Sr ²⁺ 2%, Na ⁺ 1.4%) were added to the chitosan-gelatin aqueous solution with a mass ratio of 1:3 and stirred well, and the ultrafine particles were mixed with The mass ratio of organic matter in the solution is 1:8, and it is prepared into a composite solution with an ultrafine particle concentration of 30 mg/ml, and then electrospinning of the composite solution is performed to deposit ultrafine fibers on the polymer porous network prepared in step 2). On the grid, the spinning distance was 12 cm, the spinning voltage was 18 kV, and the spinning speed was 0.5 ml/hour to form a microfiber porous film with a thickness of 800 microns.

The preparation process flow of the above steps is shown in accompanying drawing 1, and the intermediate layer is a poly-L-lactide-caprolactone porous grid, and the lower layer and the upper layer are hyaluronic acid-gelatin-bioglass, chitosan-gelatin - Heterogeneous ion co-doped calcium magnesium silicate ceramic composite electrospun fiber porous network implantable bone injury healing bandage material. Figures 2 and 3 are the scanning electron microscope and transmission electron microscope photographs of the ultrafine fiber network, respectively, and it can be seen that the bioglass or inorganic mineral particles are attached to the fiber body.

Example 2:

1) Add mesoporous bioglass particles with a particle size of 0.50 to 1.20 μm (chemical composition: 24CaO-48SiO ₂ -12B ₂ O ₃ -2P ₂ O ₅ -6MgO-4ZnO-4Na ₂ O) to a mass ratio of 2 : 5 sodium alginate-gelatin composite solution, stir evenly, the mass ratio of ultrafine particles to organic matter is 1:15, prepare an organic-inorganic composite solution with ultrafine particles concentration of 20mg/ml, and then transfer to electrospinning In the liquid reservoir of the silk, set the spinning distance to 18 cm and the spinning voltage to 18 kV, perform electrospinning at a speed of 0.3 ml/hour, and then collect the microfiber porous film with a thickness of 150 microns on the aluminum foil carrier;

2) The organic substance used to prepare the polycaprolactone porous grid is directly placed in the material container of the three-dimensional printer, and the polymer is softened by heating and extruded out of the printing nozzle. The microfiber porous film formed in step 1) is The matrix is three-dimensionally printed with a polymer porous grid, the hexagonal hole size of the porous grid is 650 microns, and the thickness of the printed polymer porous grid is 800 microns;

3) Inorganic mineral particles with a particle size of 0.4-1.6 μm (the mole percentages of inorganic ions and acid ions contained are SiO _{3 2-42%, PO 4} ^{3- 8} %, Ca ²⁺ 38%, Mg ²⁺ 6%, Zn ²⁺ 2%, Na ⁺ 4%) was added to the chitosan-gelatin solution with a mass ratio of 1:6 and stirred evenly, and the mass ratio of ultrafine particles to organic matter in the solution was 1:10. A composite solution with an ultrafine particle concentration of 60 mg/ml was obtained, and then electrospinning of the composite solution was performed, and the ultrafine fibers were deposited on the polymer porous grid prepared in step 2), the spinning distance was 16 cm, and the spinning voltage At 12 kV, the spinning speed was 0.4 ml/hour, and a microfiber porous film with a thickness of 600 μm was formed.

The preparation of the above steps forms the middle layer as a polycaprolactone porous mesh, and the lower layer and the upper layer are sodium alginate-gelatin-bioglass, chitosan-gelatin-hetero ion co-doped calcium phosphate ceramic composite electrospinning fibers Implantable Bone Injury Healing Bandage Materials of Porous Networks.

Example 3:

1) Add mesoporous bioglass powder (24CaO-56SiO ₂ -8B ₂ O ₃ -4MgO-2ZnO-6Na ₂ O) with a particle size of 0.32 to 1.10 μm to alginic acid with a mass ratio of 2:8:1 The sodium-gelatin-polyvinylphosphoric acid composite organic solution was stirred evenly, the mass ratio of ultrafine particles to organics was 1:15, and the organic-inorganic composite solution with ultrafine particles concentration of 20 mg/ml was prepared, and then transferred to electrospinning In the silk liquid reservoir, set the spinning distance to 16 cm and the spinning voltage to 20 kV, perform electrospinning at a speed of 0.4 ml/hour, and then collect the ultrafine fibers with a thickness of 280 microns on the aluminum foil drum carrier. film;

2) The organic matter used to prepare the sodium carboxymethyl cellulose porous grid is directly placed in the material container of the three-dimensional printer, and the polymer is softened by heating and extruded out of the printing nozzle, and the microfiber porous mesh formed in step 1) is used. The film is used as the substrate for three-dimensional printing of polymer porous grids. The pores of the porous grids are circular, the pore diameter is 800 microns, and the thickness of the polymer porous grids after printing is 400 microns;

3) Inorganic mineral particles with a particle size of 0.02 to 1.80 μm (the mole percentages of inorganic ions and ^acid ions contained are SiO ₃ 2-4%, PO ₄ ^3- 36%, Ca ²⁺ 46%, Mg ²⁺ 6%, Zn ²⁺ 2%, crystallization water 6%) was added to the chitosan-gelatin solution with a mass ratio of 1:3 and stirred evenly, and the mass ratio of ultrafine particles to organic matter in the solution was 1:10, Prepare a composite solution with an ultrafine particle concentration of 80 mg/ml, and then perform electrospinning of the composite solution, depositing ultrafine fibers on the polymer porous grid prepared in step 2), the spinning distance is 16cm, spinning The voltage was 16 kV, and the spinning speed was 0.6 ml/hour to form a microfiber porous film with a thickness of 400 μm.

The preparation of the above steps forms the intermediate layer as a polycaprolactone porous grid, and the lower layer and the upper layer are sodium alginate-gelatin-polyvinylphosphoric acid-bioglass, chitosan-gelatin-hetero ion co-doped calcium magnesium silicic acid Implantable Bone Injury Healing Bandage Materials of Salt-Ceramic Composite Electrospun Fiber Porous Networks.

Example 4:

1) Add mesoporous bioglass particles (chemical composition: 24CaO-50SiO ₂ -18B ₂ O ₃ -6MgO-2ZnO) with a particle size of 0.2 to 0.8 μm to sodium alginate-gelatin- The polyvinylphosphoric acid composite organic solution was stirred evenly, the mass ratio of ultrafine particles to organics was 1:10, and the organic-inorganic composite solution with ultrafine particles concentration of 20 mg/ml was prepared, and then transferred to the electrospinning storage solution In the device, set the spinning distance to 12cm and the spinning voltage to 14kV, perform electrospinning at a speed of 0.3ml/hour, and then collect the microfiber porous film with a thickness of 200 microns on the aluminum foil drum;

2) The organic substance used for preparing the polylactic acid porous grid is directly placed in the material container of the three-dimensional printer, and the polymer is softened by heating and extruded out of the printing nozzle, and the microfiber porous film formed in step 1) is used as the matrix. Three-dimensional printing of polymer porous grids, the size of the rectangular pores of the porous grids is 400 × 600 microns, and the thickness of the printed polymer porous grids is 600 microns;

3) Inorganic mineral particles with a particle size of 0.6-1.20 μm (the mole percentages of inorganic ions and acid ions contained are SiO ₃ ^2-40 %, PO ₄ ^3- 10%, Ca ²⁺ 34%, Mg ²⁺ 10%, Zn ²⁺ 2%, Sr ²⁺ 4%) was added to the carboxymethyl chitosan-gelatin solution with a mass ratio of 1:3 and stirred evenly, and the mass ratio of ultrafine particles to organic matter in the solution was 1 : 10, prepare a composite solution with an ultrafine particle concentration of 60 mg/ml, and then perform electrospinning of the composite solution, depositing ultrafine fibers on the polymer porous grid prepared in step 2), and the spinning distance is 18cm , the spinning voltage was 12 kV, and the spinning speed was 0.5 ml/hour to form a microfiber porous film with a thickness of 400 μm.

The preparation of the above steps forms the middle layer as a polylactic acid porous grid, and the lower layer and the upper layer are respectively sodium alginate-gelatin-polyvinylphosphoric acid-bioglass, carboxymethyl chitosan-gelatin-hetero ion co-doped calcium magnesium silicon Implantable Bone Injury Healing Bandage Material with Electrospun Fiber Porous Networks of Salt-Ceramic Composites.

Examples 5 to 13:

Similar to the preparation steps of Example 1, the compositions of the mesoporous bioglass, inorganic mineral particles and polymer porous meshes in Examples 5 to 13 are as follows, and the others are the same as those of Example 1, to obtain implantable bone injury healing bandage materials.

Experimental verification of the embodiment:

1. Antibacterial test

The bandage materials of Example 1, Example 2, and Example 3 were cut into sheets with a diameter of 10 mm, added to the watch dishes inoculated with Staphylococcus aureus respectively without sterilization, and placed at a distance, and continued in an anaerobic environment. Incubate for 8-24 hours, and observe the formation of the bacteriostatic ring. As shown in the results of FIG. 4 , the bandage material has a significant inhibitory effect on the growth of this bacteria, and the antibacterial rate is not less than 75% to 99% at 8, 16 and 24 hours.

2. Femoral defect repair experiment in diabetic animals

A living animal model of diabetic adult New Zealand white rabbits, weighing about 2.5 kg, was injected intravenously with sodium pentobarbital, and fixed on the operating table after anesthesia. The femoral periosteum was peeled off, the femoral shaft cortical bone was cut, and part of the periosteum was cut out, and then covered with the implanted bandage materials of Example 1 and Example 2. Control groups 1 and 2 were pure chitosan film for wound repair and Gelatin film, suture wounds and postoperative management according to routine procedures. The test results showed that all animals had good vital signs during this period, and the survival rate was 100%; as shown in Figure 5, the femoral shaft periosteum-femoral cortical bone defect healed well 6 weeks after the operation, especially in Example 1, the periosteum was completely repaired. , the degree of periosteal vascularization was high, and the cortical bone was partially healed, and the repair efficiency of the periosteum was lower in the control group. From this experiment, it can be seen that the implanted bandage material of the present invention has excellent ability to simultaneously repair soft and hard tissues.

Claims (9)

1. An implant bandage material for promoting bone injury repair, comprising:

the implant bandage material for promoting bone injury repair is of a multilayered porous network structure, the lower layer mainly comprises a superfine fiber porous network containing bioglass particles, the middle layer mainly comprises a polymer porous grid, the upper layer mainly comprises a superfine fiber porous network containing inorganic mineral particles, and the pore channels of the fiber porous network and the polymer porous grid are respectively in the levels of 0.30-1200 mu m and 200-1800 mu m.

2. An implant bandage material for promoting bone injury repair as claimed in claim 1, wherein: the particle size of the bioglass particles is 0.04-8 mu m, and the particle size of the inorganic mineral particles is 0.02-20 mu m.

3. An implant bandage material for promoting bone injury repair as claimed in claim 1, wherein: the bioglass particles are formed by taking silicon oxide and boron oxide prepared by adding a mesoporous structure guiding agent by a sol-gel method as mesoporous structure frameworks, adding multiple oxides into the mesoporous structure frameworks, and hybridizing the multiple oxides into a full glass state or partial glass state substance in the mesoporous structure frameworks, wherein the main component is SiO ₂-B₂O₃-CaO-MgO。

4. An implant bandage material for promoting bone injury repair as claimed in claim 1, wherein: the inorganic mineral particles mainly comprise calcium phosphate, calcium silicate, calcium magnesium silicate, calcium-zinc silicate, magnesium phosphate and zinc phosphate.

5. An implant bandage material for promoting bone injury repair as claimed in claim 4, wherein: the inorganic mineral particles further contain Cu²⁺、Zn²⁺、Sr²⁺And Na⁺One or more of the ions are doped with ions.

6. An implant bandage material for promoting bone injury repair as claimed in claim 5, wherein: the inorganic mineral particles comprise the following inorganic metal ions and acid radical ions in parts by mole:

SiO₃ ^2-/PO₄ ^3-1 to 54 parts

Ca²⁺1 to 60 portions

Mg²⁺0 to 52 parts by weight

Zn²⁺0 to 20 parts of

Cu²⁺0.6 to 6 portions

Sr²⁺0 to 12 parts of

Na⁺0 to 8 portions of

The rest is crystal water.

7. A preparation method of an implant bandage material for promoting bone injury repair is characterized by comprising the following steps:

1) adding biological glass particles into an organic matter solution, uniformly stirring, wherein the mass ratio of the biological glass particles to the organic matter is 1 (2-80), preparing an organic-inorganic compound solution with the concentration of ultrafine particles of 1-100 mg/ml, transferring the organic-inorganic compound solution into a liquid storage device of electrostatic spinning, setting the spinning distance to be 5-18 cm, carrying out electrostatic spinning at the spinning voltage of 4-20 kV and the speed of 0.10-0.8 ml/h, and collecting an ultrafine fiber porous film with the thickness of 10-400 microns on a receiving carrier of the liquid storage device;

2) Directly placing organic matters for preparing the polymer porous grids into a material device of a three-dimensional printer, heating to soften the organic matters, extruding out a printing nozzle, and performing three-dimensional printing on the polymer porous grids on the upper surface by taking the superfine fiber porous films formed in the step 1) as matrixes;

3) adding inorganic mineral particles into an organic matter solution, uniformly stirring, wherein the mass ratio of the inorganic mineral particles to the organic matter is 1 (2-80), preparing a compound solution with the concentration of ultrafine particles of 1-100 mg/ml, then carrying out electrostatic spinning on the compound solution, and depositing ultrafine fibers on the upper surface of the polymer porous grid prepared in the step 2), wherein the spinning distance is 4-15 cm, the spinning voltage is 4-20 kV, and the spinning speed is 0.10-1.0 ml/h, so as to form the implantation bandage material with the thickness of 10-800 micrometers.

8. The method for preparing an implant bandage material for promoting bone injury repair of claim 7, wherein: the receiving carrier is a porous metal aluminum foil or copper foil, the pore channel is any one or the combination of two of a triangle, a quadrangle, a hexagon, a circle and a honeycomb, and the pore size is 0.3-2000 microns.

9. Use of an implant bandage material for promoting the repair of bone injuries according to claims 1 to 6 or of an implant bandage material for promoting the repair of bone injuries obtained by the process according to claims 7 to 8, characterized in that:

The implanted bandage material for promoting bone injury repair is applied to pharmacy in autonomous inflammation diminishing, autonomous antibiosis and efficient healing or regeneration repair of muscle tissues, periosteum tissues and bone tissues.

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