Ovine forestomach matrix (OFM), marketed as AROA ECM, is a layer of decellularized extracellular matrix (ECM) biomaterial isolated from the propria submucosa of the rumen of sheep.Lun, S., et al., A functional extracellular matrix biomaterial derived from ovine forestomach. Biomaterials, 2010. 31(16): p. 4517-29.High Tech Wound Care Company Aroa Releases First Product in Own Backyard. 2020. [Retrieved 25 Sep 23]. Available from: https://www.nzherald.co.nz/business/high-tech-wound-care-company-aroa-releases-first-product-in-own-backyard/JDMEGIPXYMBLIVGHVBNAROMRTU/ OFM is used in tissue engineering and as a tissue scaffold for wound healing and surgical applications.'Sounds like science fiction': Aroa Biosurgery uses sheep to help humans heal. 2022. [Retrieved 25 Sep 2023]. Available from: https://www.stuff.co.nz/business/industries/127888238/sounds-like-science-fiction-aroa-biosurgery-uses-sheep-to-help-humans-healSheep guts powering Kiwi firm to ASX float. 2020. [Retrieved 7 Nov 23]. Available from: https://7news.com.au/business/ipos/sheep-guts-powering-kiwi-firm-to-asx-float-c-1122610
History OFM was developed and is manufactured by Aroa Biosurgery Limited (New Zealand, formerly Mesynthes Limited, New Zealand)Clever Kiwi Companies Out to Prove that Technology can Save Money as well as Many Peoples Lives. 2010. [Retrieved 25 Sep 2023]. Available from: https://www.nzherald.co.nz/business/clever-kiwi-companies-out-to-prove-that-technology-can-save-money-as-well-as-many-peoples-lives/TVVQSE7OCZOPTRM3EJ2U3FCYXY/ and was first patented in 2008Ward, B.R., K.D. Johnson, and B.C.H. May, Tissue scaffolds derived from forestomach extracellular matrix, USPTO, Editor. 2008, Mesynthes Ltd.: US. and described in the scientific literature in 2010.Lun, S., et al., A functional extracellular matrix biomaterial derived from ovine forestomach. Biomaterials, 2010. 31(16): p. 4517-29. OFM is manufactured from sheep rumen tissue, using a process of decellularization to selectively remove the unwanted sheep cells and cell components to leave an intact and functional extracellular matrix.From Tripe, a Kiwi Medical Innovation. 2019. [Retrieved 25 Sep 2023]. Available from: https://www.stuff.co.nz/science/117957242/from-tripe-a-kiwi-medical-innovation OFM comprises a special layer of tissue found in rumen, the propria submucosa, which is structurally and functionally distinct from the submucosa of other gastrointestinal tissues.Well healed. 2023. [Retrieved 7 Nov 23]. Available from: https://www.callaghaninnovation.govt.nz/customer-stories/well-healedFranco, A.J., et al., Morphometric and immunohistochemical study of the rumen of red deer during prenatal development. J Anat, 2004. 204(6): p. 501-13
OFM was first cleared by the FDA in 2009 for the treatment of wounds.FDA approves biologic template for tissue regeneration. 2010. [Retrieved 7 Nov 23]. Available from: https://www.dermatologytimes.com/view/fda-approves-biologic-template-tissue-regeneration.Premarket notification, 510(k) : K092096. 2010; Available from: . Since 2008 there have been >70 publications describing OFM and its clinical applications, and over 6 million clinical applications of OFM-based devices.Aroa Biosurgery December 2022 4C - Commentary.Auckland High Tech Wound Care Company Makes Maiden Profit as Sales Double to 24m. 2020. [Retrieved 25 Sep 2023]. Available from: https://www.nzherald.co.nz/business/auckland-high-tech-wound-care-company-makes-maiden-profit-as-sales-double-to-24m/TRELCVONB6OZ5IXIOI7UVD26YY/
Composition OFM comprises more than 24 collagens (most notably types I and III), but also contains many growth factors, polysaccharides and proteoglycans that naturally exist as part of the extracellular matrix and play important roles in wound healing and soft tissue repair.'Sounds like science fiction': Aroa Biosurgery uses sheep to help humans heal. 2022. [Retrieved 25 Sep 2023]. Available from: https://www.stuff.co.nz/business/industries/127888238/sounds-like-science-fiction-aroa-biosurgery-uses-sheep-to-help-humans-healBadylak, S.F., The extracellular matrix as a biologic scaffold material. Biomaterials, 2007. 28(25): p. 3587-93 The composition includes more than 150 different proteins,Using agricultural byproducts to heal complex wounds. 2023. [Retrieved 7 Nov 23]. Available from: https://www.seetomorrowfirst.nz/domestic/news/aroa-using-agricultural-byproducts-to-heal-complex-wounds including elastin, fibronectin, glycosaminoglycans, basement membrane components, and various growth factors, such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and platelet derived growth factor (PDGF).Dempsey, S.G., et al., Functional Insights from the Proteomic Inventory of Ovine Forestomach Matrix. J Proteome Res, 2019. 18(4): p. 1657-1668 OFM has been shown to recruit mesenchymal stem cells,Aroa’s Endoform gains validation to recruit stem cells. 2020. [Retrieved 7 Nov 23]. Available from: https://www.biospectrumasia.com/news/36/16555/aroas-endoform-gains-validation-to-recruit-stem-cells.htmlDempsey, S.G., et al., A novel chemotactic factor derived from the extracellular matrix protein decorin recruits mesenchymal stromal cells in vitro and in vivo. PLoS One, 2020. 15(7): p. e0235784. stimulate cell proliferation, angiogenesis and vascularogenesis,Irvine, S.M., et al., Quantification of in vitro and in vivo angiogenesis stimulated by ovine forestomach matrix biomaterial. Biomaterials, 2011. 32(27): p. 6351-61 and modulate matrix metalloproteinase and neutrophil elastase.Negron, L., S. Lun, and B.C.H. May, Ovine forestomach matrix biomaterial is a broad spectrum inhibitor of matrix metalloproteinases and neutrophil elastase. Int Wound J, 2012. 11(4): p. 392-397 The porous structure of OFM has been characterized by differential scanning calorimetry (DSC),Sizeland, K.H., et al., Collagen Fibril Response to Strain in Scaffolds from Ovine Forestomach for Tissue Engineering. ACS Biomater. Sci. Eng., 2017. 3(10): p. 2550–2558. scanning electron microscopy (SEM),Lun, S., et al., A functional extracellular matrix biomaterial derived from ovine forestomach. Biomaterials, 2010. 31(16): p. 4517-29.Sizeland, K.H., et al., Collagen Fibril Response to Strain in Scaffolds from Ovine Forestomach for Tissue Engineering. ACS Biomater. Sci. Eng., 2017. 3(10): p. 2550–2558. atomic force microscopy (AFM),Smith, M.J., et al., Further structural characterization of ovine forestomach matrix and multi-layered extracellular matrix composites for soft tissue repair. J Biomater Appl, 2021. 36(6): p. 996-1010 histology,Lun, S., et al., A functional extracellular matrix biomaterial derived from ovine forestomach. Biomaterials, 2010. 31(16): p. 4517-29. Sirius Red staining,Sizeland, K.H., et al., Collagen Fibril Response to Strain in Scaffolds from Ovine Forestomach for Tissue Engineering. ACS Biomater. Sci. Eng., 2017. 3(10): p. 2550–2558. small-angle x-ray scattering (SAXS),Sizeland, K.H., et al., Collagen Fibril Response to Strain in Scaffolds from Ovine Forestomach for Tissue Engineering. ACS Biomater. Sci. Eng., 2017. 3(10): p. 2550–2558.Floden, E.W., et al., Biophysical characterization of ovine forestomach extracellular matrix biomaterials. J Biomed Mater Res B Appl Biomater, 2010. 96(1): p. 67-75. and micro computerized topography (MicroCT).Smith, M.J., et al., Further structural characterization of ovine forestomach matrix and multi-layered extracellular matrix composites for soft tissue repair. J Biomater Appl, 2021. 36(6): p. 996-1010Remond, D., F. Meschy, and F. Boivin, Metabolites, water and mineral exchanges across the rumen wall: Mechanisms and regulation. Annales de Zootechnie, 1996. 45(2): p. 97-119. OFM has been shown to contain residual vascular channels that facilitate blood vessel formation through angioconduction.Smith, M.J., et al., Further structural characterization of ovine forestomach matrix and multi-layered extracellular matrix composites for soft tissue repair. J Biomater Appl, 2021. 36(6): p. 996-1010.Kiwi biotech makes its mark in asx debut. 2021. [Retrieved 7 Nov 23]. Available from: https://www.investsmart.com.au/investment-news/kiwi-biotech-makes-its-mark-in-asx-debut/148404
Tissue engineering OFM can be fabricated into a range of different product presentations for tissue engineering applications, and can be functionalized with therapeutic agents including silver,Karnik, T., et al., Ionic silver functionalized ovine forestomach matrix - a non-cytotoxic antimicrobial biomaterial for tissue regeneration applications. Biomater Res, 2019. 23(6): p. 17. doxycyclineMay, B.C.H., C.H. Miller, and B.R. Ward, Collagen-Based Device Having Antifungal Properties, USPTO, Editor. 2016, Aroa Biosurgery Ltd.: US. and hyaluronic acid.Smith, M.J., et al., Further structural characterization of ovine forestomach matrix and multi-layered extracellular matrix composites for soft tissue repair. J Biomater Appl, 2021. 36(6): p. 996-1010. OFM has been commercialized as single and multi-layered sheets, reinforced biologics and powders.Aroa Biosurgery Web Page. 2023 [cited 2023 27 February 2023]; Available from: https://aroa.com/.TELA Bio rolls out new OviTex resorbable for implantation. 2023. [Retrieved 7 Nov 2023]. Available from: https://www.medicaldevice-network.com/news/tela-bio-ovitex-resorbable-implantation/?cf-view
When placed in the body OFM does not elicit a negative inflammatory response and is absorbed into the regenerating tissues via a process called tissue remodeling.TELA Bio starts commercialization for large size OviTex reinforced bioscaffolds. 2019. [Retrieved 7 Nov 23]. Available from: https://www.nsmedicaldevices.com/news/tela-bio-aroa-biosurgery-ovitex-rbss/Auckland High Tech Wound Care Company Makes Maiden Profit as Sales Double to 24m. 2020. [Retrieved 25 Sep 2023]. Available from: https://www.nzherald.co.nz/business/auckland-high-tech-wound-care-company-makes-maiden-profit-as-sales-double-to-24m/TRELCVONB6OZ5IXIOI7UVD26YY/TELA Bio rolls out new OviTex resorbable for implantation. 2023. [Retrieved 7 Nov 2023]. Available from: https://www.medicaldevice-network.com/news/tela-bio-ovitex-resorbable-implantation/?cf-view
Clinical significance Wound healing Aroa Biosurgery Limited first distributed OFM commercially in 2012 as Endoform™ Dermal Template (later Endoform™ Natural) through a distribution partnership with Hollister Incorporated (IL, USA). Endoform™ Natural and Endoform™ Antimicrobial (0.3% ionic silver w/w), are single layers of OFM used in the treatment of acute and chronic wounds, including diabetic foot ulcers (DFU)Bosque, B.A., et al., Retrospective real-world comparative effectiveness of ovine forestomach matrix and collagen/ORC in the treatment of diabetic foot ulcers. Int Wound J, 2022. 19(4): p. 741-753. and venous leg ulcers (VLU).Bohn, G.A. and K. Gass, Leg ulcer treatment outcomes with new ovine collagen extracellular matrix dressing: a retrospective case series. Adv Skin Wound Care, 2014. 27(10): p. 448-54. Endoform™ Natural has been shown to accelerate wound healing of DFU.Bosque, B.A., et al., Retrospective real-world comparative effectiveness of ovine forestomach matrix and collagen/ORC in the treatment of diabetic foot ulcers. Int Wound J, 2022. 19(4): p. 741-753. The wound product Symphony™ combines OFM and hyaluronic acid and is designed to support healing during the proliferative phase particularly in patients whose healing is severely impaired or compromised due to disease.Smith, M.J., et al., Further structural characterization of ovine forestomach matrix and multi-layered extracellular matrix composites for soft tissue repair. J Biomater Appl, 2021. 36(6): p. 996-1010.
Complex plastics and reconstructive surgery