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WO-2026091068-A1 - Collagen Compositions and Uses Thereof

WO2026091068A1WO 2026091068 A1WO2026091068 A1WO 2026091068A1WO-2026091068-A1

Abstract

The present invention relates to collagen-based compositions and methods for the preparation and use of said compositions. The compositions may find application in, but are not limited to, sealing and/or repairing tissue, delivering agents to tissue, and/or culturing cells.

Inventors

  • You, Jingjing
  • SUTTON, GERARD
  • HUA, Sheng
  • Fan, Jiawen
  • Simunovic, Matthew

Assignees

  • THE UNIVERSITY OF SYDNEY
  • EYE AND ENT HOSPITAL OF FUDAN UNIVERSITY

Dates

Publication Date
20260507
Application Date
20241101

Claims (20)

  1. A composition comprising: - 5-24 mg/ml collagen; - 0.04-0.15 M sodium ions and/or 0.008-0.4 M calcium ions; and - 0.0005-0.05 mg/ml riboflavin, wherein the collagen comprises type I collagen, type II collagen and/or type IV collagen.
  2. The composition of claim 1, wherein the composition comprises about 0.005 mg/ml riboflavin.
  3. A composition comprising: - 5-24 mg/ml collagen; - 0.04-0.15 M sodium ions and/or 0.008-0.4 M calcium ions; and - platelet lysate, wherein the collagen comprises type I collagen, type II and/or type IV collagen.
  4. The composition of claim 3, wherein the composition comprises 0.01%-40%(v/v) platelet lysate.
  5. A composition comprising: - 5-24 mg/ml collagen; - 0.04-0.15 M sodium ions and/or 0.008-0.4 M calcium ions; and - fibrinogen, wherein the collagen comprises type I collagen, type II and/or type IV collagen.
  6. The composition of claim 5, wherein the composition comprises 0.01-4 mg/ml fibrinogen.
  7. The composition of any one of claims 1 to 6, wherein the composition further comprises mammalian cells.
  8. The composition of claim 7, wherein the mammalian cells comprise or consist of human cells.
  9. The composition of claim 7 or claim 8, wherein the mammalian cells comprise any one or more of: neuronal cells, neuroglial cells, epithelial cells, photoreceptor cells, Müller cells, endothelial cells, retinal pigment epithelial cells, therapeutic cells.
  10. The composition of any one of claims 1 to 9, further comprising any one or more of: a culture medium, growth factors such as brain derived growth factor and neuronal growth factor, hormones, matrix proteins, glycoproteins, vitamins, ions other than sodium ions or calcium ions, ion sources, fibronectin, amino acids, antibiotics, anaesthetics, factor XIII, Fetal Bovine Serum (FBS) , Fetal Calf Serum (FCS) , human serum, therapeutic drugs such as neuroprotective, antifibrotic, anti-apoptotic, anti-vascular and regenerative medications, nucleic acids.
  11. The composition of any one of claims 1 to 10, wherein the collagen is neutralised.
  12. A method of preparing a composition, the method comprising: (i) providing a first solution comprising: - collagen, wherein the collagen comprises type I, type II collagen and/or type IV collagen; and - sodium ions and/or calcium ions; (ii) providing a second solution comprising riboflavin; and (iii) combining the first solution and the second solution, wherein the composition comprises: - 6-24 mg/ml of the collagen; - 0.04-0.15 M of the sodium ions and/or 0.008-0.4 M of the calcium ions; and - 0.0005-0.05 mg/ml of the riboflavin.
  13. A method of preparing a composition, the method comprising: (i) providing a solution comprising: - 6-24 mg/ml collagen, wherein the collagen comprises type I, type II collagen and/or type IV collagen; - 0.0005-0.05 mg/ml riboflavin; and - 0.04-0.15 M sodium ions and/or 0.008-0.4 M calcium ions; (ii) applying the solution to a surface; and (iii) activating the riboflavin.
  14. The method of claim 13, wherein applying the solution to a surface forms a layer, and wherein steps (ii) and (iii) are repeated a plurality of times, wherein each layer is applied on top of the preceding layer.
  15. The method of any one of claims 12 to 14, wherein the composition comprises about 0.005 mg/ml riboflavin.
  16. The method of any one of claims 13 to 15, wherein the activating in step (iii) comprises applying light capable of activating the riboflavin.
  17. A method of preparing a composition, the method comprising: (i) providing a first solution comprising: - collagen, wherein the collagen comprises type I, type II collagen and/or type IV collagen; and - sodium ions and/or calcium ions; (ii) providing a second solution comprising platelet lysate; and (iii) combining the first solution and the second solution, wherein the composition comprises: - 6-24 mg/ml of the collagen; - 0.04-0.15 M of the sodium ions and/or 0.008-0.4 M of the calcium ions; and - the platelet lysate.
  18. The method of claim 17, wherein the composition comprises 0.01%-40% (v/v) platelet lysate.
  19. A method of preparing a composition, the method comprising: (i) providing a first solution comprising: - collagen, wherein the collagen comprises type I, type II collagen and/or type IV collagen; and - sodium ions and/or calcium ions; (ii) providing a second solution comprising fibrinogen; and (iii) combining the first solution and the second solution, wherein the composition comprises: - 6-24 mg/ml of the collagen; - 0.04-0.15 M of the sodium ions and/or 0.008-0.4 M of the calcium ions; and - the fibrinogen.
  20. The method of claim 19, wherein the composition comprises 0.01-4 mg/ml fibrinogen.

Description

Collagen Compositions and Uses Thereof Technical Field The present invention relates generally to the fields of biology and medicine. More specifically, the present invention relates to compositions suitable for sealing and/or repairing tissue, methods for the production thereof and methods for the use thereof. Without limitation, compositions described herein may also be suitable for the delivery of agents to biological targets such as tissues and cells and/or for culturing cells. However, it will be appreciated that the invention is not limited to these particular fields of use. Background The following discussion of the prior art is provided to place the invention in an appropriate technical context and enable the advantages of it to be more fully understood. It should be appreciated, however, that any discussion of the prior art throughout the specification should not be considered as an express or implied admission that such prior art is widely known or forms part of the common general knowledge in the field. Collagens, a group of structural proteins, are the most abundant proteins in the human body. Collagens are found in connective tissue, skin, tendons, bones, and cartilage. They provide structural support to tissues and play an important role in cellular processes such as tissue repair, intercellular communication and cellular migration. Whilst collagens are not transparent in the skin, the organization of collagen fibrils is largely responsible for the transparency and refraction of the cornea, lens and vitreous body of the eye, and the structural strength of the eye can predominantly be attributed to collagens present in the sclera. Tissue degeneration as a result of disease and injury to tissue resulting from trauma have traditionally been treated using replacement tissue from a suitable donor. However, lack of availability of suitable donor tissue can severely limit the process. More recently, bioengineering has afforded an alternative means for the replacement and/or repair of biological tissue. Bioengineering allows for the creation of synthetic substitute tissue prior to transplantation. The structural properties and potential for transparency of collagens described above have led to the application of this group of proteins as biomaterials. One disadvantage of the use of collagen-based biomaterials is the requirement for crosslinking of the collagen fibrils in order to achieve the required mechanical strength. Options available to crosslink collagen include physical crosslinking, chemical crosslinking, electro-compaction and photocrosslinking. However, each of the aforementioned methods has its drawbacks. Physical crosslinking generally results in lower optical properties for applications involving the eye. Chemical crosslinking methods may be toxic to cells. Electro-compaction results in a reduction in mechanical strength. Photocrosslinking can be slow and photosensitizing agents may be toxic to cells and/or affect the transparency of the biomaterials. A need exists for collagen-based biomaterials with improved properties. Rhegmatogenous retinal detachment (RRD) is a severe, potentially vision-threatening disease. RRD refers to tearing of the retina which can lead to irreversible vision loss and requires immediate surgery. Such tears are one of the main causes of retinal blindness worldwide, resulting in a significant social and economic burden. Generally, RRD is preceded by breaks in the retina, through which subretinal fluid can accumulate in the potential space between the neurosensory retina and the underlying retinal pigment epithelial (RPE) cells and lead to inflammation and proliferative vitreoretinopathy (PVR) . The release of pigmentary epithelial cells and glial cells through retinal breaks leads to the formation of epiretinal, intraretinal or subretinal membranes with strong contractile power, which then damage the function of the retina. Sealing retinal breaks completely during surgery could prevent PVR and RRD recurrence. Current RRD surgical treatment includes vitrectomy, laser and tamponade. However, none of these methods seal the breaks completely and as a result, RPE exposure still exists after surgery. A need exists to improve the performance of surgery for RRD. It is an object of the present invention to overcome or ameliorate one or more the disadvantages of the prior art, or at least to provide a useful alternative. Summary of the Invention The present invention alleviates at least one of the problems associated with the production and effective use of collagen-based biomaterials. The present inventors have surprisingly developed collagen-based biomaterials which can be crosslinked in a short time and/or with the use of a low concentration of a photosensitizing agent and/or with the use of heat. In the context of retinal and neural tissue, the inventors have surprisingly found that a biomaterial comprising collagen is compatible with cells, e.g., retinal pigment epithe