Dura-mater biological patch and preparation method thereof

Abstract

The invention discloses a dura-mater biological patch and a preparation method thereof. The dura-mater biological patch adopts a process of using small intestinal submucosa tissues as materials and systemically removing immunogenic substances. The preparation method comprises the following steps of: using alcohol to treat and remove lipids, using trypsin and alkali solution to treat and remove cells, using DNA enzyme to treat and remove DNA, and using alpha-galactosidase to treat and remove alpha-Gal antigens and the like. The dura-mater biological patch and the preparation method disclosed by the invention have the advantages that not only can the immunogenic substances be effectively removed, but also the normal structure of extracellular matrix can not be damaged; and when the dura-mater biological patch is clinically applied in repairing dura-mater defects, the leakage of cerebrospinal fluid can be effectively prevented, the tissue can be guided for ingrowth, the tissue growing speed is matched with the patch decomposing speed, the immunological rejection is low and the biocompatibility is good.

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 that protects the tissue of the brain (spinal cord) and prevents 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 community to repair the dura mater through surgery to maintain the integrity of the dura mater, protect the brain (spinal cord) tissue, and prevent cerebrospinal...

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

Invention patent CN 103272275B uses inbred animal small intestinal submucosa tissue as raw material to ensure the stability and uniformity of different batches of products, removes residual DNA by mechanical oscillation and ultrasonic oscillation technology, and overcomes the problem of relatively large DNA residues in Biodesign Surgisis products The problem is that the DNA residue of the patented product is 120±15pg / g, which is significantly lower than the 250±45pg / g of Biodesign Surgisis DNA residue, but the decellularization and degreasing process of the patent only uses a low concentration of alkaline solution in a short period of time. Time treatment, decellularization and delipidation are not effective, and there is no process involved in the removal of α-Gal antigen

Invention patents CN101366975 B and CN 101366979 B used peracetic acid disinfection, alkaline solution decellularization, DNase and α-galactosidase treatment processes for SIS materials, although the removal of immunogenic substances DNA and α-Gal antigen was considered , but its decellularization and degreasing process is only short-term alkaline solution treatment, the effect is not good

Invention patent CN 103405811 B includes steps such as disinfection, trypsin, DNase and α-galactosidase treatment on the SIS material, but does not involve the degreasing process

Invention patent CN 101433735 B adopts "peracetic acid + ethanol" disinfection, organic solvent degreasing, "hyperosmotic treatment + trypsin treatment + acid treatment + alkali treatment" decellularization and surfactant descaling and other processes for SIS materials, However, 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 trypsin concentration in this process is too high and the treatment time is too long, which may damage the extracellular matrix. structure; and the inventive process does not involve steps to remove DNA and α-Gal antigen

[0012] To sum up, currently there is 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 content of immunogenic substances in the product and easily lead to Immunotoxicity after implantation

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