A scanning electron microscopy (SEM) image highlighting the complex collagenous microarchitecture underlying the luminal surface of OFM.
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.[1][2] OFM is used in tissue engineering and as a tissue scaffold for wound healing and surgical applications.[3][4]
History
OFM was developed and is manufactured by Aroa Biosurgery Limited (New Zealand, formerly Mesynthes Limited, New Zealand)[5] and was first patented in 2008[6] and described in the scientific literature in 2010.[7] 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.[8] 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.[9][10]
OFM was first cleared by the FDA in 2009 for the treatment of wounds.[11][12] Since 2008 there have been >70 publications describing OFM and its clinical applications, and over 6 million clinical applications of OFM-based devices.[13][14]
OFM can be fabricated into a range of different product presentations for tissue engineering applications, and can be functionalized with therapeutic agents including silver,[35]doxycycline[36] and hyaluronic acid.[37] OFM has been commercialized as single and multi-layered sheets, reinforced biologics and powders.[38][39]
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).[43] 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)[44] and venous leg ulcers (VLU).[45] Endoform™ Natural has been shown to accelerate wound healing of DFU.[46][47] 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[48][49]
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™)[50][51][52] and powdered format (Myriad Morcells™).[53][54] OFM-based surgical devices are routinely used in complex lower extremity reconstruction,[55] pilonidal sinus reconstruction,[56] hidradenitis suppurativa[57] 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 skin[58][59][60]
Hernia repair
Multi-layered OFM devices, reinforced with synthetic polymer were first described in 2008[61] and in the scientific literature in 2010.[62] 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 Inc.[63][64] Clinical studies have shown that OFM reinforced biologics have lower hernia recurrence rates versus synthetic hernia meshes[65][66][67] or biologics[68] such as acellular dermis.
References
^Lun, S., et al., A functional extracellular matrix biomaterial derived from ovine forestomach. Biomaterials, 2010. 31(16): p. 4517-29.
^Franco, 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
^Dempsey, 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.
^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
^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
^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.
^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.
^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
^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.
^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.
^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
^Remond, 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.
^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.
^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.
^May, B.C.H., C.H. Miller, and B.R. Ward, Collagen-Based Device Having Antifungal Properties, USPTO, Editor. 2016, Aroa Biosurgery Ltd.: US.
^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.
^Aroa Biosurgery Web Page. 2023 [cited 2023 27 February 2023]; Available from: https://aroa.com/.
^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.
^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.
^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.
^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.
^Premarket notification, 510(k) : K200502. 2021; Available from: [3].
^Bosque, 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).
^Chaffin, 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.
^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.
^Bohn, 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)
^Ward, B.R., K.D. Johnson, and B.C.H. May, Tissue scaffolds derived from forestomach extracellular matrix, USPTO, Editor. 2008, Mesynthes Ltd.: US.
^Floden, 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.
^Parker, 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.
^Sivaraj, 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.
