Thermosensitive material for promoting vascularization of small intestinal submucosa and preparation method thereof

Abstract

The invention provides a small intestinal submucosa-based vascularization promoting thermosensitive material. The small intestinal submucosa-based vascularization promoting thermosensitive material is prepared by packaging a small intestinal submucosa matrix and a dissolving solution, respectively, wherein the small intestinal submucosa matrix is obtained through the following steps: performing enzymatic hydrolysis, acid dissolution and freeze-drying on the small intestinal submucosa, and then crushing and sterilizing the small intestinal submucosa to obtain a sterile powdery or flocculent small intestinal submucosa matrix material; the dissolving solution consists of phosphate buffer containing NaOH or normal saline. According to the invention, the two matrixes of the small intestinal submucosa-based vascularization promoting thermosensitive material both can be preserved for a long time and are mixed in an appropriate ratio before in use; the thermosensitive material has excellent injectability and is capable of forming a stable gel at 37 DEG C without cross-linking polymerization; the thermosensitive material is proven to have the effect of promoting vascularization by both experiments in vitro and vivo.

Description

technical field [0001] The invention relates to a temperature-sensitive material for promoting vascularization based on small intestinal submucosa and a preparation method thereof. Background technique [0002] Hydrogel is a gel with water as the dispersion medium. It has a water content close to normal tissue and good biocompatibility. Its physical and chemical properties are controllable and it has a porous structure. Its three-dimensional porous structure is very similar to the extracellular matrix. , is conducive to cell growth, proliferation and differentiation, and is also conducive to the maintenance of the activity of biologically active factors. It can be minimally invasively implanted and has broad application prospects in tissue engineering. Thermosensitive hydrogel can change from liquid state to gel state within a certain temperature range, without other catalysts and severe reaction conditions, can well fill various irregular-shaped tissue defects, and can even...

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Problems solved by technology

Hurst et al. prepared SIS gel, the method mainly including: enzymatic hydrolysis, acid dissolution, 10mM HCl dialysis, etc., sterilized by chloroform dialysis, and then neutralized with sterile NaOH to obtain the gel [Hurst, R.E.; Hauser, P.J.; Kyker, K.D., et al.Suppression and Activation of the Malignant Phenotype by Extracellular Matrix in Xenograft Models of Bladder Cancer: A Model for TumorCell "Dormancy".PLoS One,2013,8(5):e6418], this method is very cumbersome , need aseptic operation to add sterile NaOH to neutralize HCl before use; and the purpose of its dialysis is to make the HCl in the solution reach 10mM, which takes a long time; in addition, the gel prepared by this method is not suitable for long-term storage

[0004] In summary, the SIS gel prepared by the current method can form a gel in vivo, but it is difficult to form a stable gel in vitro. If it is directly used on the wound surface of the body surface, the SIS will not be able to effectively stay on the wound surface, which is not conducive to the formation of the gel on the body surface. Wound repair; moreover, 75% ethanol, chloroform, etc. are commonly used for sterilization, and the product form is liquid, which is not suitable for mass production [UniltedStates Patent (10) Patent No.: US 8,361,503 B2]; For storage, the product will form a colloidal state with time at room temperature, lose its fluidity, and is not suitable for long-term storage; if the unneutralized solution is stored, although the storage time can be extended, aseptic operation is required to add sterile NaOH, And measure its pH value, the operation is cumbersome and unfavorable for application

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