Ovine Forestomach Matrix

Ovine forestomach matrix (OFM) (marketed as AROA ECMTM) is a layer of decellularized extracellular matrix (ECM) biomaterial isolated from the propria submucosa of the rumen of sheepLun, 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-heal.
==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 2010Lun, 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 matrixFrom 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 tissuesFranco, 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 woundsPremarket notification, 510(k) : K092096. 2010; Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K092096.. Since 2008 there have been >70 publications describing OFM and its clinical applications, and over 6 million clinical applications of OFM-based devicesAroa 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, 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 cellsDempsey, 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 vascularogenesisIrvine, 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 elastaseNegron, 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, histologyLun, S., et al., A functional extracellular matrix biomaterial derived from ovine forestomach. Biomaterials, 2010. 31(16): p. 4517-29., Sirius Red stainingSizeland, 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 angioconductionSmith, 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..
==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 silverKarnik, 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 acidSmith, 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 powdersAroa Biosurgery Web Page. 2023 [cited 2023 27 February 2023]; Available from: https://aroa.com/.. 
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 remodelingAuckland 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/. 
==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)Aroa Biosurgery tipped for IPO at $300m valuation. 2020. [Retrieved 25 Sep 2023]. Available from: https://www.nzherald.co.nz/business/aroa-biosurgery-tipped-for-ipo-at-300m-valuation/HVHFJ24MYSELY6A62WSADNNCTQ/. Endoform™ Natural and Endoform™ Antimicrobial (0.3% ionic silver w/w), are single layers of OFM is 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 DFUBosque, 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.. 
===Complex Plastics and Reconstructive Surgery===
OFM was cleared by the FDA in 2016 and 2021 for surgical applications in plastics and reconstructive surgery as a multi-layered product (Myriad Matrix™)Aroa Biosurgery Expands Options for Soft Tissue Repair with Launch of Myriad. 2020. [Retrieved 25 Sep 23]. Available from: https://www.scoop.co.nz/stories/SC2002/S00048/aroa-biosurgery-expands-options-for-soft-tissue-repair-with-launch-of-myriad.htm Premarket notification, 510(k) : K153632. 2016; Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K153632.Premarket notification, 510(k) : K153633. 2016; Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K153633. and powdered format (Myriad Morcells™)New Zealand's Aroa Biosurgery Takes Wound Technology to the World. 2021. [Retrieved 25 Sep 2023]. Available from: https://www.asx.com.au/blog/listed-at-asx/new-zealands-aroa-biosurgery-takes-wound-technology-to-the-world Premarket notification, 510(k) : K200502. 2021; Available from: https://www.fda.gov/medical-devices/510k-clearances/march-2021-510k-clearances.. OFM-based surgical devices are routinely used in complex lower extremity reconstructionBosque, B.A., et al., Ovine Forestomach Matrix in the Surgical Management of Complex Lower-Extremity Soft-Tissue Defects. J Am Podiatr Med Assoc, 2023. 113(3)., pilonidal sinus reconstructionChaffin, A.E., et al., Surgical reconstruction of pilonidal sinus disease with concomitant extracellular matrix graft placement: a case series. J Wound Care, 2021. 30(Sup7): p. S28-S34., hidradenitis suppurativaChaffin, A.E. and M.C. Buckley, Extracellular matrix graft for the surgical management of Hurley stage III hidradenitis suppurativa: a pilot case series. J Wound Care, 2020. 29(11): p. 624-630. and complex traumatic wounds.
OFM-based surgical devices are routinely used in plastics and reconstructive surgery for the regeneration of soft tissues when used as an artificial skinBohn, G.A. and A.E. Chaffin, Extracellular matrix graft for reconstruction over exposed structures: a pilot case series. J Wound Care, 2020. 29(12): p. 742-749.Chaffin, A.E. and M.C. Buckley, Extracellular matrix graft for the surgical management of Hurley stage III hidradenitis suppurativa: a pilot case series. J Wound Care, 2020. 29(11): p. 624-630.Desvigne, M.N., et al., Case Report: Surgical Closure of Chronic Soft Tissue Defects Using Extracellular Matrix Graft Augmented Tissue Flaps. Frontiers in Surgery, 2020. 7(173).
===Hernia Repair===
Multi-layered OFM devices, reinforced with synthetic polymer were first described 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 in the scientific literature in 2010Floden, E.W., et al., Biophysical characterization of ovine forestomach extracellular matrix biomaterials. J Biomed Mater Res B Appl Biomater, 2011. 96(1): p. 67-75.. These devices, termed ‘reinforced biologics’ have been designed for applications in the surgical repair of hernia as an alternative to synthetic surgical mesh (a mesh prosthesis). OFM reinforced biologics are distributed in the US by Tela Bio IncTela Bio Wins FDA Nod for Ovitex Hernia Repair Bioscaffold. 2016. [Retrieved 25 Sep 2023]. Available from: https://www.massdevice.com/tela-bio-wins-fda-nod-ovitex-hernia-repair-bioscaffold/?utm_source=TrendMD&utm_medium=cpc&utm_campaign=Mass_Device_TrendMD_0. Clinical studies have shown that OFM reinforced biologics have lower hernia recurrence rates versus synthetic hernia meshesParker, M.J., et al., A novel biosynthetic scaffold mesh reinforcement affords the lowest hernia recurrence in the highest-risk patients. Surg Endosc, 2020. 35(9): p. 5173-5178.Sivaraj, D., et al., Outcomes of Biosynthetic and Synthetic Mesh in Ventral Hernia Repair. Plast Reconstr Surg Glob Open, 2022. 10(12): p. e4707. or biologicsSivaraj, D., et al., Reinforced Biologic Mesh Reduces Postoperative Complications Compared to Biologic Mesh after Ventral Hernia Repair. Plast Reconstr Surg Glob Open, 2022. 10(2): p. e4083. such as acellular dermis.
Category:Compatibility layers
Category:Extracellular matrix
Category:Biomaterials