Dura mater biopatch and preparation method thereof

Abstract

The invention discloses a dura mater biopatch and a preparation method thereof. The method comprises the following steps: A) separating the small intestinal submucosa of an animal; A2) degreasing: immersing the small intestinal submucosa in ethanol having a concentration of 90-100% at normal temperature under an ultrasonic condition for 0.5-12 h; A3) performing any one or more of decellularization, DNA removal, alpha-Gal antigen removal and alkali treatment; and A4) performing freeze drying and disinfection. The dura mater biopatch is prepared through the method. The invention concretely provides the dura mater biopatch prepared from the SIS (small intestinal submucosa), having low content of an immunogen substance and being able to reserve the three-dimensional structure of a natural extracellular matrix, and the preparation method thereof.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a biological patch for dura mater defect repair and a preparation method thereof. Background technique [0002] The dura mater is an important barrier to protect brain (spinal cord) tissue and prevent leakage of cerebrospinal fluid. Dural defects are quite common in clinical neurosurgery. Trauma, tumor erosion, inflammatory damage, congenital diseases, brain surgery, spinal cord surgery, etc. can cause dural defects, which in turn lead to cerebrospinal fluid leakage, subcutaneous hemorrhage / effusion , The incision is delayed and unhealed, intracranial infection, brain tissue swelling, epilepsy and other complications. Therefore, for a long time, it has become a consensus in the neurosurgery field to repair the dura mater through surgery to maintain the integrity of the dura mater, protect the brain (spinal cord) tissue, and prevent cerebrospinal fluid leakage. Th...

AI Technical Summary

Problems solved by technology

[0007] Collagen membrane extracted from bovine tendon can be used for dura mater defect repair. Several such products have been launched in China, but this kind of material has the following disadvantages when used in dura mater repair: the degradation rate is too fast, and the material is degraded before the tissue grows; The toughness is poor and it is easy to break; the adhesion is not strong enough, and the cerebrospinal fluid can seep out from the gap around the application, forming a fluid accumulation; when it is applied to the defect site, it is infiltrated by tissue fluid, and the position cannot be adjusted, which requires more user experience. high

However, most of its processing needs to be treated with chemical agents such as epoxy or glutaraldehyde, which has the following disadvantages: potential cytotoxicity; repeated cleaning before use to remove chemical residues; slow degradation rate, which does not match tissue regeneration , can lead to complications such as fibrosis, chronic inflammation, and adhesion to the skull or brain tissue; the texture is hard and cannot fit perfectly with the surface of the brain tissue, and must be sutured tightly

The Chinese patent with the publication number CN 103272275, a biological patch and its preparation method, uses the small intestinal submucosa tissue of inbred animals as raw material to ensure the stability and uniformity of different batches of products, and uses mechanical oscillation and ultrasonic oscillation technology Removal of residual DNA overcomes the problem of high DNA residues in Biodesign Surgisis products. The DNA residues of this patented product are 120±15pg / g, significantly lower than the 250±45pg / g of Biodesign Surgisis DNA residues, but the patented The decellularization and degreasing process only uses a low concentration of alkaline solution for a short period of time, the decellularization and degreasing effect is not good, and it does not involve the process of removing α-Gal antigen

Chinese patent with publication number CN 101366975, preparation method of decellularized small intestinal submucosa biological material and Chinese patent with publication number CN 101366979, a tissue patch and its preparation method. The SIS material is sterilized with peracetic acid, alkaline solution Although the process of decellularization, DNase and α-galactosidase treatment considers the removal of immunogenic substances DNA and α-Gal antigen, the decellularization and degreasing process is only a short-term alkaline solution treatment, and the effect is not good

The Chinese patent with the publication number CN 103405811, an anti-adhesion biofilm and its preparation method, although the treatment of SIS materials includes steps such as disinfection, trypsin, DNase and α-galactosidase treatment, but does not involve degreasing craft

The Chinese patent with the publication number CN 101433735 is a preparation method of SIS tissue repair materials. Although the SIS materials are disinfected with "peracetic acid + ethanol", organic solvent degreasing, "hypertonic treatment + trypsin treatment + acid treatment + Alkali treatment” decellularization and surfactant descaling and other processes, but this process uses highly toxic organic solvents for degreasing. If the organic solvents are not removed completely, there may be a potential risk of tissue toxicity; the concentration of trypsin in this process If the temperature is too high and the treatment time is too long, the extracellular matrix structure may be damaged; and the inventive process does not involve the step of removing DNA and α-Gal antigen

[0012] To sum up, there is currently no process for the preparation of SIS that can completely consider the removal of immunogenic substances such as residual cells, lipids, DNA, and α-Gal antigens, which may cause excessive immunogenic substance content in the product and easily lead to Immunotoxicity after implantation

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