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CN-121987584-A - Stem cell active factor capsule for tissue repair and regeneration

CN121987584ACN 121987584 ACN121987584 ACN 121987584ACN-121987584-A

Abstract

The invention relates to the technical field of tissue repair and regeneration and regenerative medicine, and discloses a stem cell active factor capsule for tissue repair and regeneration, which comprises a capsule body, a carrier core body and a carrier body, wherein the capsule body is provided with a core-shell-targeting composite structure and sequentially comprises a carrier core body, an exosome containing mesenchymal stem cells, and at least one recombinant growth factor is loaded on the surface of the exosome; the intelligent shell layer is wrapped outside the load core body, and the invention uses the stem cell exosome to carry the growth factors to cooperatively activate the human body self-repairing mechanism, breaks through the limitation that the traditional method only relieves symptoms, and realizes the functional regeneration of tissues. The intelligent shell layer targeting delivery remarkably reduces immune rejection and systemic side effects and solves the shortage of donors. The drug can support multiple routes of administration such as oral administration, intravenous injection and the like, has good tolerance for patients, improves the utilization rate of enzyme-sensitive protection, and effectively overcomes the pain points of poor targeting and insufficient absorption of the traditional delivery.

Inventors

  • ZHONG ZHIQIANG
  • ZHONG CHUNSHENG

Assignees

  • 钟志强

Dates

Publication Date
20260508
Application Date
20260122

Claims (9)

  1. 1. The stem cell active factor capsule for tissue repair and regeneration is characterized by comprising a capsule body (1), wherein the capsule body (1) is provided with a core-shell-targeting composite structure and sequentially comprises the following components from inside to outside: A loaded core body (101) comprising an exosome derived from mesenchymal stem cells, the exosome surface being loaded with at least one recombinant growth factor; The intelligent shell layer (102) is wrapped outside the load core body (101), the intelligent shell layer (102) is formed by a biopolymer cross-linked network containing an enzyme-sensitive polypeptide sequence, and the enzyme-sensitive polypeptide sequence can be specifically cut by matrix metalloproteinase overexpressed at a damaged part; And the targeting functional layer (103) is covered outside the intelligent shell layer (102), and the surface of the targeting functional layer is modified with a specific targeting ligand which can recognize and bind with adhesion molecules with high expression of damaged tissue vascular endothelial cells.
  2. 2. The stem cell active factor capsule for tissue repair and regeneration according to claim 1, wherein the exosome-loaded recombinant growth factor is at least one selected from vascular endothelial growth factor, hepatocyte growth factor, transforming growth factor-beta 3.
  3. 3. The stem cell active factor capsule for tissue repair and regeneration according to claim 1, wherein the enzyme-sensitive polypeptide sequence is selected from GPQGIAGQ, PLGLWA or GPLGVRG and is specifically cleavable by matrix metalloproteinase-2 or matrix metalloproteinase-9.
  4. 4. The stem cell active factor capsule for tissue repair and regeneration according to claim 1, wherein the biopolymer of the intelligent shell layer (102) is hyaluronic acid or polyethylene glycol, and the enzyme-sensitive polypeptide sequence is connected to the biopolymer chain through a covalent bond and forms a three-dimensional network structure through a crosslinking agent.
  5. 5. The stem cell active factor capsule for tissue repair and regeneration according to claim 4, wherein the specific targeting ligand is an anti-ICAM-1 single chain antibody, an anti-VCAM-1 mimetic peptide, or a cyclic RGD polypeptide.
  6. 6. The stem cell active factor capsule for tissue repair and regeneration according to claim 1, wherein the thickness of the intelligent shell layer (102) is 100-300 nm, and the thickness of the targeting function layer (103) is 50-90 nm.
  7. 7. The stem cell active factor capsule for tissue repair and regeneration according to claim 1, wherein the capsule body (1) has an overall hydration kinetics particle size of 250-450 nm and a polydispersity index of particle size distribution of less than 0.12.
  8. 8. The stem cell active factor capsule for tissue repair and regeneration according to claim 1, wherein the capsule body (1) has a particle diameter change rate of less than 10% after incubation in phosphate buffer solution of ph7.4 at 37 ℃ for 24 hours.
  9. 9. Stem cell active factor capsule for tissue repair and regeneration according to claim 1, wherein the capsule body (1) can be administered by intravenous injection, topical injection or oral route.

Description

Stem cell active factor capsule for tissue repair and regeneration Technical Field The invention relates to the technical field of tissue repair and regeneration medicine, in particular to a stem cell active factor capsule for tissue repair and regeneration. Background Tissue injury and functional loss are major challenges facing clinical medicine, relate to a plurality of fields such as trauma, degenerative diseases, surgical operation complications and the like, and traditional treatment means such as pharmaceutical intervention, surgical repair and organ transplantation can relieve partial symptoms, but often have inherent defects such as limited curative effect, large side effect, source shortage, immune rejection, incapacity of realizing functional regeneration and the like, so that development of a novel treatment strategy capable of actively promoting the self-repairing and regeneration capacity of a human body has become a core target of regenerative medicine; At present, the traditional medicine and the growth factor delivery system lack of targeting and are easy to distribute in the whole body, so that the curative effect is limited, and systemic side effects can be possibly caused, the local concentration can be improved by local injection, but the traditional medicine and the growth factor delivery system are invasive, have poor tolerance to patients, are difficult to act on deep or diffuse damaged areas, have low transdermal absorption efficiency of external preparations, are difficult to act on internal organs, have immune rejection, ethical disputes, tumor formation risks and low survival rate when stem cells are directly transplanted, so we propose a stem cell active factor capsule for tissue repair and regeneration to solve the problems. Disclosure of Invention Aiming at the defects of the prior art, the invention provides a stem cell active factor capsule for tissue repair and regeneration, which solves the problems that the traditional medicine and the growth factor are poor in delivery targeting and easy to cause systemic side effect, the local injection is strong in invasiveness and limited in action range, the external preparation is difficult to be absorbed transdermally and act on viscera, and the stem cell is directly transplanted to face the defects of immune rejection, ethics, tumor formation, low survival rate and the like. The invention aims at realizing the aim by adopting the following technical scheme that the stem cell active factor capsule for tissue repair and regeneration comprises a capsule body, wherein the capsule body is provided with a core-shell-targeting composite structure and sequentially comprises the following components from inside to outside: A loaded core body comprising an exosome derived from mesenchymal stem cells, the exosome surface being loaded with at least one recombinant growth factor; The intelligent shell layer is wrapped outside the load core body and is formed by a biopolymer cross-linked network containing an enzyme-sensitive polypeptide sequence, and the enzyme-sensitive polypeptide sequence can be specifically cut by matrix metalloproteinase overexpressed at a damaged part; The targeting functional layer is covered outside the intelligent shell layer, and the surface of the targeting functional layer is modified with a specific targeting ligand which can recognize and combine with adhesion molecules which are highly expressed by vascular endothelial cells of damaged tissues. Preferably, the exosome-loaded recombinant growth factor is selected from at least one of vascular endothelial growth factor, hepatocyte growth factor, transforming growth factor- β3. Preferably, the enzyme-sensitive polypeptide sequence is selected from GPQGIAGQ, PLGLWA or GPLGVRG and is specifically cleavable by matrix metalloproteinase-2 or matrix metalloproteinase-9. Preferably, the biopolymer of the intelligent shell layer is hyaluronic acid or polyethylene glycol, and the enzyme-sensitive polypeptide sequence is connected to the biopolymer chain through a covalent bond and forms a three-dimensional network structure through a cross-linking agent. Preferably, the specific targeting ligand is an anti-ICAM-1 single chain antibody, an anti-VCAM-1 mimetic peptide, or a cyclic RGD polypeptide. Preferably, the thickness of the intelligent shell layer is 100-300 nanometers, and the thickness of the targeting functional layer is 50-90 nanometers. Preferably, the capsule body has an overall hydration kinetics particle size of 250-450 nm and a polydispersity index of the particle size distribution of less than 0.12. Preferably, the capsules have a particle size change of less than 10% after incubation in phosphate buffer at ph7.4 at 37 ℃ for 24 hours. Preferably, the capsule body may be administered by intravenous injection, topical injection or oral route. Advantageous effects The invention provides a stem cell active factor capsule for tissue repair and regeneration. Compare