rhCollagen

Overview

Collagen is an essential building block of the human body, providing structural support and biological signals to connective tissues and organs, and therefore it is a crucial component for tissue regeneration.

To date, collagen has been extracted from animal and human cadaver sources, baring risk of contamination and allergic response and subjected to harsh purification conditions resulting in irreversible modifications impeding its biofunctionality. Yet, the highly complex and stringent post-translational processing of collagen has prevented the development of large-scale recombinant expression systems.

CollPlant is the first company to succeed in developing a plant platform that effectively expresses human collagen.

The production of our recombinant human Type I collagen (rhCollagen) starts in the genetically engineered tobacco plants. The recombinant human protein in the form of “procollagen” is extracted from the leaves of mature plants and further processed to achieve a highly purified rhCollagen that can be used for the production of medical products.

rhCollagen – The gold standard scaffold for tissue regeneration

Our rhCollagen is identical to the type I collagen produced by the human body, making it the ideal building block for regenerative medicine. It has significant advantages over the currently available tissue-derived collagens, including improved biofunctionality, high homogeneity, and reduced risk of immune response.

 

Plant-derived rhCollagen

Clear advantages over animal-derived collagen

Animal Extracted

Plant Derived


Few cell binding domains due to partially denatured crosslinked collagen

Many cell binding domains enabled by perfect triple helix enhance cellular attachment

Slow cell proliferation and slow tissue repair Foreign body reactions (e.g. granuloma)
Fast cell proliferation and fast tissue repair

Better Bio-Functionality

  • Accelerates human cell proliferation
  • Faster tissue healing

Superior Homogeneity

  • Controlled physical / rheological properties
  • Reproducibility

Improved Safety and Greater Purity

  • Non-immunogenic
  • Non-allergenic
  • No pathogens
  • No foreign body response

 

Molecular, physical and biological characterization*

Production of type I human collagen is a complex process, starting at the intra-cellular level, with the synthesis of the correct mRNA, translation into the primary amino acid sequence, post translational modifications and assembly of a stable procollagen. Conversion of the extracted procollagen into collagen via enzymatic digestion is followed by purification.

Extensive studies done to characterize the protein at the different stages confirmed its identity to human collagen at the molecular, physical and biological levels, specifically:

  • DNA inserts of the 5 genes translated into human sequence of COLα1 and COLα2 and relevant hydroxylation profile.
  • Secondary / tertiary structural identity of the mature collagen.
  • Expected functions at the structural and biological levels including fibrillogenesis, support of cells adhesion and proliferation and non-immunogenic.
  • Superiority over animal & human tissue extracted collagen in physical and biological properties. 

The following diagram illustrates the various characterization studies conducted, demonstrating rhCollagen identity to human collagen.

Applications

rhCollagen can be fabricated in different forms, shapes, and physical properties. Applications include BioInks for 3D bioprinting of organs, tissues and scaffolds as well as products aimed at aesthetic medicine, orthopedics, advanced wound care and others.

We are advancing collaborations with leading companies in the regenerative medicine field, through licensing of our rhCollagen technology platform for the development of ground-breaking products.


*Sources:
  1. 1.  Adopted from H.J. Seeherman et al., A BMP/Activin Chimera is superior to native BMPs and induces bone repair in non-human primates when delivered in a composite matrix. Sci Transl Med 11, eaar4953 (2019)
  2. 2.  Majumdar S. et al., Influence of collagen source on fibrillar architecture and properties of vitrified collagen membranes. J Biomed Mater Res Part B (2015)
  3. 3.  Shilo S., Roth S., Amzel T., Harel-Adar T., Tamir E., Grynspan F., Shoseyov O. Cutaneous wound healing after treatment with plant-derived human recombinant collagen flowable gel. Tissue Eng Part A. 19(13-14):1519-26 (2013)
  4. 4.  Stein H, et al., Production of bioactive, post-translationally modified, heterotrimeric, human recombinant type-I collagen in transgenic tobacco. Biomacromolecules (2009)
  5. 5.  Willard JJ. et al., Plant-derived human collagen scaffolds for skin tissue engineering. Tissue Eng Part A. 19(13-14):1507-18 (2013)

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