Targeted & controlled bone healing
Fibrin Matrix Platform
Fibrin is a natural biomaterial and the main structural component of blood clots. Fibrin acts as a healing matrix and promotes tissue repair while restoring tissue function. Through a natural polymerization mechanism, fibrin is formed by the conversion of a soluble precursor (fibrinogen) to a solid degradable matrix.
As a commercial product, fibrin sealants (without biologics) have been used for more than 30 years, primarily for the prevention of blood loss during a variety of surgical procedures. Based on this clinical experience, fibrin sealants are considered to be very safe with a long history of use and a well-documented safety profile.
Kuros’ key proprietary technology platform is based on the local, covalent attachment of biologics into this fibrin matrix, Kuros’ TG-Hook technology.
Kuros’ TG-Hook technology
Kuros’ TG-Hook technology enables covalent linking of biologics, such as growth factors, to fibrin-based biomaterials, while allowing their controlled release by natural enzymes in the tissue. Using this technology, the biologics become an integral part of the biomaterial. The mechanism used for covalently linking biologics is derived from the natural blood clotting process. A transglutaminase (TG) enzyme called Factor XIIIa is responsible for cross-linking fibrin molecules, thereby forming a solid matrix, whose normal function is to stop blood loss. Kuros’ products employ this same mechanism to cross-link biologics into fibrin during the formation of the fibrin polymer. The TG-Hook technology is further designed to release the biologic upon cellular infiltration into the matrix.
There are several advantages to this approach.
- The material solidifies and cross-links in-situ to adopt the shape of the defect it is being administered to, which also allows administration into smaller or more complex defects and access sites (e.g. fine fractures and minimally invasive spinal procedures) or by spray or foam.
- The cross-linking mechanism is entirely biocompatible as it employs the natural blood clotting process, thereby preventing any local tissue damage while maintaining the functional integrity of the biological.
- The composite is mainly composed of fibrin, which is nature’s healing matrix, thereby promoting natural healing based on cellular infiltration.
- The resulting product has the required biologic covalently incorporated, ensuring local retention, as well as minimizing systemic exposure and effects on surrounding tissues.
- The biologic has been designed to only become active when it is cleaved from the fibrin matrix by infiltrating proteases – hence the material has been designed to be effective in response to the local healing mechanism and only become available locally and at the rate of the local healing process.
- Because the polymer is composed of natural materials, it ultimately degrades completely leaving only healed tissue.
Publications on Fibrin-Based Technologies
Cunningham BW, Schense J, Murgatroyd AA, McAfee PC.
An Investigational Study of a Novel Parathyroid Hormone Based Bone Graft Substitute for Interbody Spinal Fusion: An In Vivo Ovine Mode.
Podium Presentation. North American Spine Society Annual Meeting, San Francisco, Oct. 2015 Lyon T, Garcia FB, Bohatyrewciz A, Casa de Pantoja V, Detre Z, Dresing K, Dubrana F, Giannoudis P, Gorecki A, Gunther T, Harries T, Hax PM, Krettek C, Kwiatkowski K, Vence ML, Magyari Z, Mathevon H, Messmer P, Mohanty K, Montanez E, Pace A, Patel A, Piltz S, Pohl A, Rando A, Raschke M, Roussignol X, Horst S, Varga E, Widuchowski J, Zagh I, Schense J.
A novel PTH based bone graft substitute demonstrates non-inferiority to autograft in a large phase IIb study of Tibial Plateau Fractures.
Podium Presentation. Orthopedic and Trauma Association Annual Meeting, San Diego, Oct. 2015 Schense J, von Rechenberg B, Stauber M, Ferguson S.
Novel PTH based Bone Graft Substitute for treatment of fractures – results from a large ovine Tibial Plateau Defects study
Podium Presentation. Orthopedic and Trauma Association Annual Meeting, San Diego, Oct. 2015 Mittermayr R, Slezak P, Haffner N, Smolen D, Hartinger J, Hofmann A, Schense J, Spazierer D, Gampfer J, Goppelt A, Redl H.
Controlled release of fibrin matrix-conjugated platelet derived growth factor improves ischemic tissue regeneration by functional angiogenesis.
Acta Biomater. 2015 Oct 20. pii: S1742-7061(15)30158-6. Mittermayr R, Branski L, Moritz M, Jeschke MG, Herndon DN, Traber D, Schense J, Gampfer J, Goppelt A, Redl H.
Fibrin biomatrix-conjugated platelet-derived growth factor AB accelerates wound healing in severe thermal injury.
J Tissue Eng Regen Med. 2013 May 31. Mueller TL, Wirth AJ, van Lenthe GH, Goldhahn J, Schense J, Jamieson V, Messmer P, Uebelhart D, Weishaupt D, Egermann M, Müller R.
Mechanical stability in a human radius fracture treated with a novel tissue-engineered bone substitute: a non-invasive, longitudinal assessment using high-resolution pQCT in combination with finite element analysis.
J Tissue Eng Regen Med. 2011 May;5(5):415-20. Richards PJ, Turner AS, Gisler SM, Kraft S, Nuss K, Mark S, Seim HB 3rd, Schense J.
Reduction in postlaminectomy epidural adhesions in sheep using a fibrin sealant-based medicated adhesion barrier.
J Biomed Mater Res B Appl Biomater. 2010 Feb;92(2):439-46 Arrighi I, Mark S, Alvisi M, von Rechenberg B, Hubbell JA, Schense JC.
Bone Healing Induced by Local Delivery of an engineered parathyroid hormone prodrug
Biomaterials. 2009 Mar;30(9):1763-71 Mark S, Schense J; Watson J, Arrighi I, Hubbell JA, Andrianaly NH, von Rechenberg B.
Enhancement of Bone Healing by Locally Delivered Parathyroid Hormone Fusion Peptide in a Diaphyseal Defect in the Sheep Tibia
Orthopedic Research Society Annual Meeting 2007 Fuerst A, Derungs S, von Rechenberg B, Auer JA, Schense J, Watson J.
Use of a parathyroid hormone peptide (PTH(1-34))-enriched fibrin hydrogel for the treatment of a subchondral cystic lesion in the proximal interphalangeal joint of a warmblood filly.
J Vet Med A Physiol Pathol Clin Med. 2007 Mar;54(2):107-12. Dragieva G, Jen A, Bavand M, Hubbell JA, Fetz D, Burg G, Hafner J.
Treating venous ulcers with variant PDGF covalently bound in fibrin gel
2nd WUWHS Meeting, July 8-13 Paris, 2004. Hall H, Baechi T, Hubbell JA.
Molecular properties of fibrin-based matrices for promotion of angiogenesis in vitro.
Microvasc Res. 2001 Nov;62(3):315-26. Zisch AH, Schenk U, Schense JC, Sakiyama-Elbert SE, Hubbell JA.
Covalently conjugated VEGF--fibrin matrices for endothelialization.
J Control Release. 2001 May 14;72(1-3):101-13. Sakiyama-Elbert SE, Panitch A, Hubbell JA.
Development of growth factor fusion proteins for cell-triggered drug delivery.
FASEB J. 2001 May;15(7):1300-2. Sakiyama-Elbert SE, Hubbell JA.
Controlled release of nerve growth factor from a heparin-containing fibrin-based cell ingrowth matrix.
J Control Release. 2000 Oct 3;69(1):149-58. Schense JC, Bloch J, Aebischer P, Hubbell JA.
Enzymatic incorporation of bioactive peptides into fibrin matrices enhances neurite extension.
Nat Biotechnol. 2000 Apr;18(4):415-9. Sakiyama-Elbert SE, Hubbell JA.
Development of fibrin derivatives for controlled release of heparin-binding growth factors.
J Control Release. 2000 Apr 3;65(3):389-402. Sakiyama SE, Schense JC, Hubbell JA.
Incorporation of heparin-binding peptides into fibrin gels enhances neurite extension: an example of designer matrices in tissue engineering.
FASEB J. 1999 Dec;13(15):2214-24. Schense JC, Hubbell JA.
Cross-linking exogenous bifunctional peptides into fibrin gels with factor XIIIa.
Bioconjug Chem. 1999 Jan-Feb;10(1):75-81. Herbert CB, Nagaswami C, Bittner GD, Hubbell JA, Weisel JW.
Effects of fibrin micromorphology on neurite growth from dorsal root ganglia cultured in three-dimensional fibrin gels.
J Biomed Mater Res. 1998 Jun 15;40(4):551-9. Herbert CB, Bittner GD, Hubbell JA.
Effects of fibinolysis on neurite growth from dorsal root ganglia cultured in two- and three-dimensional fibrin gels.
J Comp Neurol. 1996 Feb 12;365(3):380-91.
An Investigational Study of a Novel Parathyroid Hormone Based Bone Graft Substitute for Interbody Spinal Fusion: An In Vivo Ovine Mode.
Podium Presentation. North American Spine Society Annual Meeting, San Francisco, Oct. 2015 Lyon T, Garcia FB, Bohatyrewciz A, Casa de Pantoja V, Detre Z, Dresing K, Dubrana F, Giannoudis P, Gorecki A, Gunther T, Harries T, Hax PM, Krettek C, Kwiatkowski K, Vence ML, Magyari Z, Mathevon H, Messmer P, Mohanty K, Montanez E, Pace A, Patel A, Piltz S, Pohl A, Rando A, Raschke M, Roussignol X, Horst S, Varga E, Widuchowski J, Zagh I, Schense J.
A novel PTH based bone graft substitute demonstrates non-inferiority to autograft in a large phase IIb study of Tibial Plateau Fractures.
Podium Presentation. Orthopedic and Trauma Association Annual Meeting, San Diego, Oct. 2015 Schense J, von Rechenberg B, Stauber M, Ferguson S.
Novel PTH based Bone Graft Substitute for treatment of fractures – results from a large ovine Tibial Plateau Defects study
Podium Presentation. Orthopedic and Trauma Association Annual Meeting, San Diego, Oct. 2015 Mittermayr R, Slezak P, Haffner N, Smolen D, Hartinger J, Hofmann A, Schense J, Spazierer D, Gampfer J, Goppelt A, Redl H.
Controlled release of fibrin matrix-conjugated platelet derived growth factor improves ischemic tissue regeneration by functional angiogenesis.
Acta Biomater. 2015 Oct 20. pii: S1742-7061(15)30158-6. Mittermayr R, Branski L, Moritz M, Jeschke MG, Herndon DN, Traber D, Schense J, Gampfer J, Goppelt A, Redl H.
Fibrin biomatrix-conjugated platelet-derived growth factor AB accelerates wound healing in severe thermal injury.
J Tissue Eng Regen Med. 2013 May 31. Mueller TL, Wirth AJ, van Lenthe GH, Goldhahn J, Schense J, Jamieson V, Messmer P, Uebelhart D, Weishaupt D, Egermann M, Müller R.
Mechanical stability in a human radius fracture treated with a novel tissue-engineered bone substitute: a non-invasive, longitudinal assessment using high-resolution pQCT in combination with finite element analysis.
J Tissue Eng Regen Med. 2011 May;5(5):415-20. Richards PJ, Turner AS, Gisler SM, Kraft S, Nuss K, Mark S, Seim HB 3rd, Schense J.
Reduction in postlaminectomy epidural adhesions in sheep using a fibrin sealant-based medicated adhesion barrier.
J Biomed Mater Res B Appl Biomater. 2010 Feb;92(2):439-46 Arrighi I, Mark S, Alvisi M, von Rechenberg B, Hubbell JA, Schense JC.
Bone Healing Induced by Local Delivery of an engineered parathyroid hormone prodrug
Biomaterials. 2009 Mar;30(9):1763-71 Mark S, Schense J; Watson J, Arrighi I, Hubbell JA, Andrianaly NH, von Rechenberg B.
Enhancement of Bone Healing by Locally Delivered Parathyroid Hormone Fusion Peptide in a Diaphyseal Defect in the Sheep Tibia
Orthopedic Research Society Annual Meeting 2007 Fuerst A, Derungs S, von Rechenberg B, Auer JA, Schense J, Watson J.
Use of a parathyroid hormone peptide (PTH(1-34))-enriched fibrin hydrogel for the treatment of a subchondral cystic lesion in the proximal interphalangeal joint of a warmblood filly.
J Vet Med A Physiol Pathol Clin Med. 2007 Mar;54(2):107-12. Dragieva G, Jen A, Bavand M, Hubbell JA, Fetz D, Burg G, Hafner J.
Treating venous ulcers with variant PDGF covalently bound in fibrin gel
2nd WUWHS Meeting, July 8-13 Paris, 2004. Hall H, Baechi T, Hubbell JA.
Molecular properties of fibrin-based matrices for promotion of angiogenesis in vitro.
Microvasc Res. 2001 Nov;62(3):315-26. Zisch AH, Schenk U, Schense JC, Sakiyama-Elbert SE, Hubbell JA.
Covalently conjugated VEGF--fibrin matrices for endothelialization.
J Control Release. 2001 May 14;72(1-3):101-13. Sakiyama-Elbert SE, Panitch A, Hubbell JA.
Development of growth factor fusion proteins for cell-triggered drug delivery.
FASEB J. 2001 May;15(7):1300-2. Sakiyama-Elbert SE, Hubbell JA.
Controlled release of nerve growth factor from a heparin-containing fibrin-based cell ingrowth matrix.
J Control Release. 2000 Oct 3;69(1):149-58. Schense JC, Bloch J, Aebischer P, Hubbell JA.
Enzymatic incorporation of bioactive peptides into fibrin matrices enhances neurite extension.
Nat Biotechnol. 2000 Apr;18(4):415-9. Sakiyama-Elbert SE, Hubbell JA.
Development of fibrin derivatives for controlled release of heparin-binding growth factors.
J Control Release. 2000 Apr 3;65(3):389-402. Sakiyama SE, Schense JC, Hubbell JA.
Incorporation of heparin-binding peptides into fibrin gels enhances neurite extension: an example of designer matrices in tissue engineering.
FASEB J. 1999 Dec;13(15):2214-24. Schense JC, Hubbell JA.
Cross-linking exogenous bifunctional peptides into fibrin gels with factor XIIIa.
Bioconjug Chem. 1999 Jan-Feb;10(1):75-81. Herbert CB, Nagaswami C, Bittner GD, Hubbell JA, Weisel JW.
Effects of fibrin micromorphology on neurite growth from dorsal root ganglia cultured in three-dimensional fibrin gels.
J Biomed Mater Res. 1998 Jun 15;40(4):551-9. Herbert CB, Bittner GD, Hubbell JA.
Effects of fibinolysis on neurite growth from dorsal root ganglia cultured in two- and three-dimensional fibrin gels.
J Comp Neurol. 1996 Feb 12;365(3):380-91.
