Search

US-20260124340-A1 - BIO-IMPLANTABLE MICROFIBER GRAFT AND METHOD OF MANUFACTURING THE SAME

US20260124340A1US 20260124340 A1US20260124340 A1US 20260124340A1US-20260124340-A1

Abstract

The present disclosure relates to a bio-implantable microfiber graft and a method of manufacturing the same. A method of manufacturing a bio-implantable microfiber graft according to an exemplary embodiment of the present disclosure includes: manufacturing a porous nanofiber membrane based on a biocompatible polymer; and manufacturing one-dimensional porous microfibers by forming the porous nanofiber membrane in a twisted structure.

Inventors

  • Geun Bae LIM
  • Jung Ho Lee

Assignees

  • CELLKNIT INC.

Dates

Publication Date
20260507
Application Date
20260105
Priority Date
20230713

Claims (20)

  1. 1 . A method of manufacturing a bio-implantable microfiber graft, the method comprising: manufacturing a porous nanofiber membrane based on a biocompatible polymer; and manufacturing one-dimensional porous microfibers by forming the porous nanofiber membrane in a twisted structure.
  2. 2 . The method of claim 1 , wherein the porous nanofiber membrane or the microfibers are coated with parylene.
  3. 3 . The method of claim 1 , further comprising: forming a nanoelectrode by depositing a conductive material on the porous nanofiber membrane.
  4. 4 . The method of claim 3 , wherein the nanoelectrode is formed in a two-dimensional multi-array structure on a surface of the porous nanofiber membrane, and a plurality of nanoelectrodes included in the multi-array structure are arranged spaced apart from each other along a longitudinal direction of the microfibers when the porous nanofiber membrane is manufactured into microfibers.
  5. 5 . The method of claim 1 , further comprising: forming the plurality of nanofiber membranes into a nanofiber bundle.
  6. 6 . The method of claim 5 , wherein the nanofiber bundle has a core having a first stiffness and a shell surrounding the core, which has a second stiffness different from the first stiffness.
  7. 7 . The method of claim 6 , wherein the core of the nanofiber bundle is formed of Polylactic Acid (PLA), and the shell is formed of Polycaprolactone (PCL).
  8. 8 . The method of claim 5 , wherein the nanofiber bundle is formed of hook-shaped nanofibers.
  9. 9 . The method of claim 5 , wherein the nanofiber bundle includes a main fiber and microfibers connected thereto.
  10. 10 . The method of claim 5 , wherein the nanofiber bundle is formed by mixing multi-layered nanofiber membranes and forming them in a rolled or twisted form.
  11. 11 . The method of claim 1 , wherein the nanofiber membrane is manufactured as a nanofiber membrane having an area equal to or greater than a predetermined critical area through multi-nozzles, so that the microfiber has a length equal to or greater than a predetermined critical length.
  12. 12 . The method of claim 3 , further comprising: loading a stimuli-responsive hydrogel onto the nanoelectrode, wherein the stimuli-responsive hydrogel contains a drug.
  13. 13 . The method of claim 12 , wherein the stimuli-responsive hydrogel is responsive to pH to release the drug.
  14. 14 . The method of claim 12 , wherein the stimuli-responsive hydrogel is responsive to an ion concentration to release the drug.
  15. 15 . The method of claim 12 , wherein the stimuli-responsive hydrogel is responsive to a glucose concentration to release the drug.
  16. 16 . The method of claim 12 , wherein the stimuli-responsive hydrogel is responsive to an antigen concentration to release the drug.
  17. 17 . The method of claim 1 , further comprising: loading functional stem cells onto the porous nanofiber membrane.
  18. 18 . The method of claim 17 , wherein a cross-section of the microfiber formed by the porous nanofiber membrane loaded with the functional stem cells is formed such that density and strength gradually change from one side to the other side.
  19. 19 . The method of claim 1 , wherein a decellularized extracellular matrix-based hydrogel of a target organ is loaded onto at least a portion of the surface of the microfiber.
  20. 20 . A bio-implantable microfiber graft comprising: one-dimensional microfibers manufactured by forming a porous nanofiber membrane formed based on a biocompatible polymer into a nanofiber bundle and then forming the nanofiber bundle in a twisted structure.

Description

CROSS-REFERENCE TO RELATED APPLICATION This application is a Continuation of International Application No. PCT/KR2024/009948, filed Jul. 11, 2024, which claims the benefit of and priority to Korean Patent Application No. 10-2024-0091587, filed on Jul. 11, 2024, and Korean Patent Application No. 10-2023-0090807, filed on Jul. 13, 2023, the entire disclosure(s) of which is hereby incorporated herein by reference in its entirety. BACKGROUND Field The present disclosure relates to a bio-implantable graft, and non-limitingly but more particularly, to a bio-implantable microfiber graft and a method of manufacturing the same which may effectively deliver drugs or cells into the body using a biocompatible microfiber. Description of Related Art Development of materials for in vivo drug delivery and tissue regeneration plays a very important role in the fields of modern pharmaceuticals and life sciences, and such materials have been researched in the direction of delivering drugs to target tissues or organs to enhance drug efficacy, promote tissue regeneration, and reduce side effects. Biodegradable materials have a characteristic of slowly degrading over time, and when utilized for drug delivery and tissue regeneration, can improve the efficacy of drug therapy and reduce side effects. A drug delivery system using such materials has generally been developed in the form of scaffolds, which are solid framework materials, and hydrogels in a liquid form. The scaffolds are implanted into lesion sites through surgical procedures and release drugs over an extended period while being gradually decomposed. However, they have limited surface area for drug incorporation, making effective drug delivery difficult due to insufficient capacity and drug release rates, and their inherent rigidity causes anatomical discomfort, and their mechanical stiffness does not match that of surrounding tissues or organs, consequently resulting in problems such as inflammation and damage to tissues or organs. Additionally, biodegradable drug delivery systems in a filler form, such as hydrogels, involve injecting a liquid gel filler through a syringe, which gradually degrades and releases drugs over an extended period. However, due to structural instability and low mechanical strength of the liquid form, it is difficult to ensure consistent drug release, and the incorporated drugs are susceptible to degradation and instability. SUMMARY As described above, among conventional materials for in vivo drug delivery and tissue regeneration, scaffolds have a limited surface area for drug incorporation, present difficulties in effective drug delivery, cause anatomical discomfort, and result in inflammation and damage to tissues or organs due to their inherent rigidity, and hydrogels, due to their low mechanical strength, make it difficult to ensure consistency of drug release and present problems of easy drug denaturation. One object of the present disclosure for solving the aforementioned problems is to provide a bio-implantable microfiber graft which has a large surface area per unit volume for high drug diffusion efficiency and flexible mechanical properties for high compatibility with tissue, and maintains its shape even after time elapses following implantation into tissue to exhibit uniform drug release characteristics, and exhibits mechanically and chemically stable storage and transport performance during a process of loading and releasing drugs. Another object of the present disclosure for solving the aforementioned problems is to provide a method of manufacturing a bio-implantable microfiber graft that simultaneously achieves a high drug loading capacity and a sustained drug release mechanism through a microporous structure that facilitates drug absorption and release, and enables drug delivery and tissue regeneration promotion in response to various environmental conditions and stimuli. However, it is to be understood that the technical problem to be solved by the present disclosure is not limited to the above problems and may be variously extended in a range which does not depart from the spirit and scope of the present disclosure. In order to achieve the above-described object, in an aspect, provided is a method of manufacturing a bio-implantable microfiber graft which may include: manufacturing a porous nanofiber membrane based on a biocompatible polymer; and manufacturing one-dimensional porous microfibers by forming the porous nanofiber membrane in a twisted structure. According to an aspect, the porous nanofiber membrane or the microfibers may be coated with parylene. The method of manufacturing the bio-implantable microfiber graft according to an exemplary embodiment of the present disclosure may further include forming nanoelectrodes by depositing a conductive material on the porous nanofiber membrane. According to an aspect, the nanoelectrode may be formed in a two-dimensional multi-array structure on a surface of the porous nanofiber m