CN-122005919-A - Degradable macroporous composite tissue engineering scaffold, structural performance regulation and control method and application

CN122005919ACN 122005919 ACN122005919 ACN 122005919ACN-122005919-A

Abstract

The invention discloses a degradable macroporous composite tissue engineering scaffold, a structural performance regulating and controlling method and application thereof, and belongs to the technical field of biomedical materials. The invention realizes the phase separation by the design of gel molecules and solvents, thereby forming a macroporous structure, adjusting the pore structure by controlling the proportion of polyvinyl alcohol aqueous solution, glycerol and hydrophilic degradable biological macromolecule aqueous solution, adjusting the mechanical property of the bracket by adding degradable inorganic micro-nano particles, and simultaneously, integrating and constructing the bracket material with the pore structure and the mechanical property having space heterogeneity by a hot melt interface. The invention solves the problems of insufficient controllability of pore structure and mechanical property and the like of the existing tissue engineering scaffold, and is suitable for being used as a degradable macroporous composite tissue engineering scaffold material for promoting the cooperative injury repair of soft and hard tissues such as osteochondral, musculoskeletal, tendinous bone and the like.

Inventors

LIN XIAO
YANG LEI
XIAO ZHE
Chu Fengcheng
LIU YUEYUE
LIU HUILING
XU HAO

Assignees

苏州大学

Dates

Publication Date: 20260512
Application Date: 20251229

Claims (6)

1. The degradable macroporous composite tissue engineering scaffold is characterized in that the preparation method thereof comprises the following steps: (1) Dissolving polyvinyl alcohol into deionized water according to the concentration of 2-8wt%, stirring for 0.5-1 hour at the temperature of 85-95 ℃, adding glycerol, continuously stirring for 0.5-1 hour at the temperature of 85-95 ℃ with the volume ratio of a polyvinyl alcohol aqueous solution to the glycerol of 1:0.4-0.6, cooling to 45-65 ℃ to obtain a solution A, adding hydrophilic degradable biological macromolecules into the deionized water according to the concentration of 1-5wt%, and stirring and heating for 0.5-2 hours at the temperature of 45-65 ℃ to obtain a solution B; (2) Mixing the solution A prepared in the step (1) and the solution B according to the volume ratio of 2-5:1, stirring for 0.5-1 hour at 45-65 ℃, adding degradable organic micro-nano particles according to the concentration of 0.1-10 wt%, stirring for 0.5-1 hour at 40-60 ℃, pouring into a mould, freezing at-80 to-20 ℃ in sequence, thawing at room temperature, freezing and thawing for 6-24 hours respectively, and repeating the freezing and thawing treatment for 1-3 times to obtain the composite organic hydrogel; (3) And (3) soaking the composite organic hydrogel prepared in the step (2) in deionized water for 6-24 hours to obtain the degradable macroporous composite tissue engineering scaffold with controllable structural performance.
2. The degradable macroporous composite tissue engineering scaffold of claim 1, wherein the hydrophilic degradable biological macromolecules are selected from one of gelatin, hyaluronic acid, sodium alginate and starch, or any combination thereof.
3. The degradable macroporous composite tissue engineering scaffold of claim 1, wherein the inorganic micro-nano particles are selected from one of magnesium oxide, zinc oxide, bioactive glass, nano-hydroxyapatite, or any combination thereof.
4. The method for regulating and controlling the structural performance of the degradable macroporous composite tissue engineering scaffold, which is disclosed in claim 1, is characterized in that the pore structure is regulated by controlling the proportion of a polyvinyl alcohol aqueous solution, glycerol and a hydrophilic degradable biological macromolecule aqueous solution, and the elastic modulus is regulated by controlling the concentration of inorganic micro-nano particles.
5. The method for regulating and controlling the structural performance of the degradable macroporous composite tissue engineering scaffold according to claim 4, wherein the pore structure is regulated within a range of 10-200 mu m in pore diameter and 65-85% in porosity, and the elastic modulus is regulated within a range of 1-600 kPa.
6. The application of the degradable macroporous composite tissue engineering scaffold in tissue repair is characterized in that according to the structural performance requirement of a material required by damaged tissue repair, the regulation and control method of claim 4 is adopted, the composite organic hydrogels with different components obtained in claim 1 are assembled, heated and bonded, and then soaked in deionized water for 6-24 hours, so that the degradable macroporous composite tissue engineering scaffold with the elasticity modulus and pore structure space heterogeneity distribution is obtained, and the degradable macroporous composite tissue engineering scaffold is applied to preparation of repair materials for treating the cooperative damage of soft and hard tissues of bone cartilage, musculoskeletal tissue and tendon.

Description

Degradable macroporous composite tissue engineering scaffold, structural performance regulation and control method and application Technical Field The invention relates to a degradable macroporous composite tissue engineering scaffold for promoting repair of bone cartilage, muscle bone and tendon bone injury, a preparation method and application thereof, and belongs to the technical field of biomedical materials. Background With the promotion of aging population and the rising incidence of accidental injury, the clinical demand for high-performance tissue repair materials is becoming urgent. The synergic injury of soft and hard tissues such as osteochondral, musculoskeletal, tendinous bone and the like is a clinically common wound type, and the repair and reconstruction of the synergic injury are all the difficulties in clinical treatment. The tissue engineering scaffold material can provide carriers and proper biological, physical and chemical signals for cell adhesion, proliferation and differentiation, guide and induce tissue regeneration, and has important application prospect in the aspect of tissue injury repair. The tissue engineering scaffold with the internally communicated macroporous structure (the pore diameter is more than 10 mu m) can provide sufficient space for cell adhesion and proliferation, and promote nutrient substance delivery and metabolite discharge. The pore structure and mechanical property of the macroporous structure tissue engineering scaffold directly affect cell functions and tissue repair quality, and particularly, different tissues have different requirements on the pore structure and mechanical property of the scaffold, so that development of a tissue engineering scaffold material with controllable and adjustable spatial heterogeneity of the pore structure and mechanical property is needed for repairing the cooperative damage of soft and hard tissues. On one hand, the preparation process of the macroporous scaffold material provided by the prior art is complex, and is not beneficial to commercial mass production, for example, chinese patent No. CN111978588A discloses a method for constructing a macroporous structure material with a pore diameter of 30-600 mu m by using gelatin microspheres as a sacrificial template, the preparation process is complex, the pore size is difficult to regulate and control, and the penetrability of pores is poor. On the other hand, since the macroporous structure belongs to structural defects in material mechanics, the macroporous structure is easier to cause material damage under the action of external force, and the mechanical property is poor, for example, the macroporous silk protein hydrogel is prepared by adopting a freezing photocrosslinking method in Chinese patent No. 114716726A, the average pore diameter of the prepared hydrogel is 70-90 mu m, but the mechanical property of the prepared silk protein frozen gel is poor, and when the silk protein concentration is 200 mg/mL, the compression modulus is about 5 kPa. The macroporous tissue engineering scaffold material which is needed in clinic and meets the requirement of controllable adjustment of spatial heterogeneity of pore structure and mechanical property is not reported at present. Literature （Facile preparation of hydrogen-bonded supramolecular polyvinyl alcohol-glycerol gels with excellent thermoplasticity and mechanical properties[J].Polymer,2017,11:168-176） reports that the organic hydrogel prepared from polyvinyl alcohol/glycerin has thermoplasticity, is hopeful to prepare a scaffold material with pore structure and mechanical property spatial heterogeneity through heating adhesion, but the pore diameter of the material is in a nano level, and does not have the characteristics of a macroporous tissue engineering scaffold material. Therefore, the existing preparation method of the macroporous scaffold is still to be improved and developed, and a pore structure and mechanical property spatial heterogeneity controllable adjustment technology is to be developed so as to promote the application of the macroporous scaffold in the field of tissue repair. Disclosure of Invention Aiming at the defects existing in the prior art, the invention provides a degradable macroporous composite tissue engineering scaffold, a preparation method and application thereof, and the controllable adjustment of the spatial heterogeneity of pore structures and mechanical properties is realized. The technical scheme for realizing the aim of the invention is to provide a degradable macroporous composite tissue engineering scaffold, and the preparation method comprises the following steps: (1) Dissolving polyvinyl alcohol into deionized water according to the concentration of 2-8wt%, stirring for 0.5-1 hour at the temperature of 85-95 ℃, adding glycerol, stirring for 0.5-1 hour at the temperature of 85-95 ℃ with the volume ratio of a polyvinyl alcohol aqueous solution to the glycerol of 1:0.4-0.6, cooling to 4