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CN-122005925-A - Porous polycaprolactone microsphere for tissue filling and preparation method thereof

CN122005925ACN 122005925 ACN122005925 ACN 122005925ACN-122005925-A

Abstract

The invention discloses a porous polycaprolactone microsphere for tissue filling and a preparation method thereof, and relates to the field of biomedical materials. The microsphere is composed of polycaprolactone, the diameter is 40-70 mu m, the discrete coefficient is less than 5%, the porosity is 55-85%, and the surface of the microsphere is provided with a uniform open pore structure formed by tridecane. The invention adopts a microfluidic technology, takes a polycaprolactone dichloromethane solution containing tridecane as a disperse phase, takes a polyvinyl alcohol aqueous solution as a continuous phase, forms an oil-in-water emulsion through micro-channel shearing, and is obtained through solidification, washing and freeze drying. The microsphere has excellent monodispersity and porous structure, can obviously promote fibroblast proliferation and collagen secretion, and induces moderate inflammatory reaction to activate tissue regeneration. The technology of the invention is simple and controllable, and the obtained microsphere has injectability and tissue repair promoting function, and has application prospect in the field of soft tissue repair.

Inventors

  • CEN LIAN
  • ZHANG JINTAO

Assignees

  • 华东理工大学

Dates

Publication Date
20260512
Application Date
20260415

Claims (10)

  1. 1. The porous polycaprolactone microsphere for tissue filling is characterized by comprising polycaprolactone, wherein the diameter of the microsphere is 40-70 mu m, the porosity of the microsphere is 55-85%, the surface of the microsphere is provided with an open pore structure formed by tridecane serving as a pore-forming agent, and the microsphere is used for promoting collagen secretion of human skin fibroblasts.
  2. 2. The porous polycaprolactone microsphere according to claim 1, wherein the intrinsic viscosity of the polycaprolactone is 0.24dl/g and the dispersion coefficient of the microsphere is less than 5%.
  3. 3. A method for preparing the porous polycaprolactone microsphere according to any one of claims 1-2, comprising the steps of: S1, preparing a dispersion phase containing tridecane, namely dissolving polycaprolactone into dichloromethane to prepare a solution with the mass fraction of 1-6wt%, and adding tridecane into the solution to prepare a mixed solution with the mass fraction of 2-6wt% of tridecane as the dispersion phase; S2, preparing a continuous phase, namely dissolving a surfactant into deionized water to prepare a solution with the mass fraction of 0.5-4wt% as the continuous phase; S3, performing microfluidic shearing to form emulsion, namely introducing a disperse phase into a micro-channel with the inner diameter of 50-300 mu m, introducing a continuous phase into the micro-channel with the inner diameter of 300-800 mu m, controlling the flow rate Q d of the disperse phase to be 0.1-10 mL/h, controlling the flow rate Q c of the continuous phase to be 1-50 mL/h, and forming oil-in-water emulsion through flow focusing or T-shaped micro-channel shearing; s4, solidifying, namely receiving the emulsion into a collection liquid, volatilizing dichloromethane through horizontal rotation, precipitating and solidifying polycaprolactone, and separating tridecane to form pores to obtain a porous microsphere precursor; S5, obtaining a product, namely washing and drying the solidified microsphere to obtain the porous polycaprolactone microsphere.
  4. 4. The preparation method of claim 3, wherein in the step S2, the surfactant is polyvinyl alcohol, and in the step S4, the collecting liquid is a polyvinyl alcohol aqueous solution with a mass fraction of 0.5-4wt%.
  5. 5. The method according to claim 3, wherein in step S3, the micro-channel is a coaxial flow focusing type or a crisscross type channel.
  6. 6. The method according to claim 3, wherein in the step S4, the rotation speed of the horizontal rotation is 40rpm to 300rpm, and the time is 24h to 72h.
  7. 7. A method according to claim 3, wherein in step S5, the drying is freeze-drying.
  8. 8. The method according to claim 3, wherein the surface porosity of the microspheres is controlled by controlling the concentration of tridecane in step S1, and the particle size of the microspheres is controlled by controlling the flow rate ratio of the dispersed phase to the continuous phase in step S3.
  9. 9. The porous polycaprolactone microsphere according to claim 1 or 2, wherein the microsphere is used for inducing a moderate inflammatory response to activate fibroblasts, promoting skin tissue regeneration.
  10. 10. Use of the porous polycaprolactone microspheres according to claim 1 or 2 for the preparation of injectable fillers for soft tissue repair or facial rejuvenation.

Description

Porous polycaprolactone microsphere for tissue filling and preparation method thereof Technical Field The invention relates to the technical field of biomedical materials, in particular to a porous polycaprolactone microsphere for tissue filling and a preparation method thereof. Background The essence of skin aging is the reduced proliferation of fibroblasts and the simultaneous degradation of extracellular matrix (e.g. collagen, elastin), leading to atrophy of soft tissues, facial contour relaxation and dishing. At present, the clinical treatment means for soft tissue volume restoration mainly comprise surgery, laser treatment and injection type tissue filling agent. Among them, injection filling has become a mainstream choice for facial rejuvenation and soft tissue repair due to its advantages of minimal trauma, rapid recovery, etc. The ideal injectable filler should have good biocompatibility, a suitable particle size range (usually 25-50 μm to avoid rapid phagocytosis of macrophages and reduce inflammatory reaction), a stable filling volume, and bioactivity to promote tissue regeneration. Polycaprolactone (PCL) is a biodegradable polyester approved by the United states FDA, and is widely applied in the fields of tissue engineering, drug delivery and regenerative medicine due to excellent biocompatibility, controllable degradation rate and good mechanical properties. The filling product with polycaprolactone microsphere as a core component can gradually degrade and stimulate collagen regeneration, so that a long-acting filling effect is realized. However, most of the prior polycaprolactone microspheres are solid microspheres prepared by a traditional emulsion solvent evaporation method or a spray drying method. The solid microspheres have obvious defects in practical application, namely, the solid microspheres have high density, are easy to deposit and locally gather in an injection preparation, cause high injection resistance, are difficult to push and even trigger local stress concentration and inflammatory reaction, and have the advantages of limited specific surface area of solid structures, weak interaction with tissue cells, slow collagen generation process and limited continuous promotion effect on tissue repair. To improve the above problems, researchers have attempted to prepare polycaprolactone microspheres having a porous structure. The porous structure can obviously increase the specific surface area of the microsphere, is favorable for cell proliferation and migration, and can provide a space template for new tissue ingrowth. At present, the preparation method of the porous microsphere mainly comprises a multiple emulsion/solvent evaporation method, a phase separation method, a spray drying method, a pore-foaming agent leaching method and the like. However, these existing methods generally have the defects of complicated process steps, poor controllability of porous structure, wide particle size distribution of the obtained microspheres, and the like, and are difficult to simultaneously meet the requirements of the tissue filler on the uniformity of particle size, injectability and bioactivity. In particular, the microspheres prepared by the conventional emulsification method have nonuniform particle size and high discrete coefficient, and are easy to cause the problems of local aggregation and nonuniform inflammatory reaction after injection. In addition, the existing research on how microsphere surface morphology affects the mechanisms of fibroblast functions (such as proliferation and collagen secretion) is not fully explored, and microsphere design strategies capable of actively regulating cell behaviors through the surface morphology are lacking. Most polycaprolactone microsphere products still stay on the physical filling action level, and the biological activity potential of the polycaprolactone microsphere products serving as the regenerative medical materials cannot be fully exerted. Therefore, the invention provides a porous polycaprolactone microsphere for tissue filling and a preparation method thereof, wherein the microsphere particle size is precisely controlled by adopting a microfluidic technology, and tridecane is used as a specific pore-forming agent to construct a uniform porous structure in and on the microsphere, so that the microsphere is endowed with biological activity which remarkably promotes proliferation of Human Skin Fibroblasts (HSFs) and secretion of collagen while realizing monodispersity (a discrete coefficient of < 5%) and proper particle size (40-70 mu m) and induces proper inflammatory reaction to activate tissue regeneration, and finally, the high-performance tissue filling material with injectability, structural stability and tissue repair promoting function is provided. Disclosure of Invention The invention aims to provide a porous polycaprolactone microsphere for tissue filling and a preparation method thereof, which are used for solving the problems o