Ovine Forestomach Matrix Research Articles

Initial experience with ovine forestomach matrix graft for glossectomy defect reconstruction: A case series

Soft tissue reconstruction of oral cavity defects, such as glossectomy defects secondary to malignancy, pose a challenge for head and neck, oral, and maxillofacial surgeons. Reconstruction options for mucosal defects include primary closure, healing by secondary intention, full mucosal and split-thickness skin grafts, pedicled flaps, and microvascular free flaps. Biological grafts have become an integral part of the modern reconstructive ladder and are widely used for the regeneration of various soft tissue defects, including oral defects. This case series describes our initial experience using ovine forestomach matrix grafts in tongue and oral cavity reconstruction. Oral reconstruction using ovine forestomach matrix grafts was undertaken on three patients post wide excision and resulted in good functional and cosmetic outcomes. The rate of tissue formation provided by the graft and the grafts’ relative resistance to the hostile environment of the oral cavity support further clinical research to validate the use of these devices in oral reconstruction.

Varying Properties of Extracellular Matrix Grafts Impact Their Durability and Cell Attachment and Proliferation in an In Vitro Chronic Wound Model

While acute wounds typically progress through the phases of wound healing, chronic wounds often stall in the inflammatory phase due to elevated levels of matrix metalloproteinases (MMPs) and proinflammatory cytokines. Dysregulated expression of MMPs can result in the breakdown of extracellular matrix (ECM) formed during the wound healing process, resulting in stalled wounds. Native collagen-based wound dressings offer a potential wound management option to sequester excess MMPs and support cellular interactions that allow wound progression through the natural healing process. Herein, we utilized commercially available ECM matrices, two derived from porcine small intestinal submucosa (PCMP, 2 layers; PCMP-XT, 5 layers) and one derived from propria submucosa (ovine forestomach matrix, OFM, 1 layer), to demonstrate the impact of processing methodologies (e.g., layering and crosslinking) on functional characteristics needed for the management of chronic wounds. Grafts were evaluated for structural composition using scanning electron microscopy and histology, ability to reduce MMPs using fluorometric assays, and durability in an in vitro degradation chronic wound model. Both intact (nondegraded) and partially degraded grafts were assessed for their ability to serve as a functional cell scaffold using primary human fibroblasts. Grafts differed in matrix substructure and composition. While all grafts demonstrated attenuation of MMP activity, PCMP and PCMP-XT showed larger reductions of MMP levels. OFM rapidly degraded in the in vitro degradation model (<3 hours), while PCMP and PCMP-XT were significantly more durable (>7 days). The ability of PCMP and PCMP-XT to serve as scaffolds for cellular attachment was not impacted by degradation in vitro. Three ECM grafts with varying structural and functional characteristics exhibited differential durability when degraded in a simulated chronic wound model. Those that withstood rapid degradation maintained their ability to function as a scaffold to support attachment and proliferation of fibroblasts, a cell type important for wound healing.

Ovine Forestomach Matrix in the Surgical Management of Complex Lower-Extremity Soft-Tissue Defects.

Chronic lower-extremity defects may lead to major amputations and have severe consequences on patient quality of life and mortality. Dermal matrices have become part of the reconstructive ladder and are often deployed in these scenarios to quickly build neodermis, especially in volumetric defects over exposed bone and tendon initially, to allow for subsequent closure by means of split-thickness skin grafting (STSG) or secondary intention. Ovine forestomach matrix (OFM) is a decellularized extracellular matrix (ECM) bioscaffold available in both sheet and particulate forms that can be used as a dermal matrix in various soft-tissue reconstruction procedures. This retrospective case series evaluated the use of OFM products in the surgical reconstruction of 50 cases (n = 50) comprised of challenging lower-extremity defects from seven healthcare centers. Patient records were reviewed to identify comorbidities, defect cause, defect size, presence of exposed structures, Centers for Disease Control and Prevention contamination score, Wagner grade, OFM graft use, time to 100% granulation tissue, STSG use, overall time to heal, and postoperative complications. The primary study outcomes were time (days) to 100% granulation tissue formation, with secondary outcomes including overall time to wound closure (weeks), STSG take at 1 week, and complications. The results of this case series demonstrate OFM as a clinically effective treatment in the surgical management of complex lower-extremity soft-tissue defects with exposed structures in patients with multiple comorbidities. One application of OFM products was effective in regenerating well-vascularized neodermis, often in the presence of exposed structures, with a mean time to 100% granulation of 26.0 ± 22.2 days. These data support the use of OFM as a safe, cost-effective, and clinically effective treatment option for coverage in complex soft-tissue wounds, including exposed vital structures, and to shorten the time to definitive wound closure in complicated patient populations.

Influence of advanced wound matrices on observed vacuum pressure during simulated negative pressure wound therapy

Biomaterials and negative pressure wound therapy (NPWT) are treatment modalities regularly used together to accelerate soft-tissue regeneration. This study evaluated the impact of the design and composition of commercially available collagen-based matrices on the observed vacuum pressure delivered under NPWT using a custom test apparatus. Specifically, testing compared the effect of the commercial products; ovine forestomach matrix (OFM), collagen/oxidized regenerated cellulose (collagen/ORC) and a collagen-based dressing (CWD) on the observed vacuum pressure. OFM resulted in an ∼50% reduction in the observed target vacuum pressure at 75 mmHg and 125 mmHg, however, this effect was mitigated to a ∼0% reduction when fenestrations were introduced into the matrix. Both collagen/ORC and CWD reduced the observed vacuum pressure at 125 mmHg (∼15% and ∼50%, respectively), and this was more dramatic when a lower vacuum pressure of 75 mmHg was delivered (∼20% and ∼75%, respectively). The reduced performance of the reconstituted collagen products is thought to result from the gelling properties of these products that may cause occlusion of the delivered vacuum to the wound bed. These findings highlight the importance of in vitro testing to establish the impact of adjunctive therapies on NPWT, where effective delivery of vacuum pressure is paramount to the efficacy of this therapy.

Cover Image

The cover image is based on the Original Article Retrospective real-world comparative effectiveness of ovine forestomach matrix and collagen/ORC in the treatment of diabetic foot ulcers by Brandon A. Bosque et al., https://doi.org/10.1111/iwj.13670.

Use of Ovine Forestomach Matrix in the Treatment of Facial Thermal Burns

Thermal burn injuries are common, devastating medical emergencies that are challenging to manage. Timely and effective treatment is paramount to both short- and long-term patient outcomes. Currently, medical providers and health care facilities worldwide are emphasizing the need for cost-efficient and accessible treatments; such treatments are particularly vital for vulnerable populations with limited access to advanced medical resources. The use of extracellular matrix (ECM) technologies has become widespread in the management of acute and chronic wounds, including burns. Ovine forestomach matrix (OFM) is an ECM bioscaffold isolated from sheep forestomach tissue and has been shown to be effective in soft tissue reconstruction procedures. The use of OFM in the treatment of 2 facial thermal burn injuries, including in a pediatric patient, is described. Both patients fully recovered from their facial injuries with satisfactory cosmetic outcomes. Although OFM technology is widely used in the management of acute and chronic wounds, the authors believe this to be the first published report of its use to aid healing in burns. Ovine forestomach matrix may provide a valuable additional tool for the management of complex burns.

Further structural characterization of ovine forestomach matrix and multi-layered extracellular matrix composites for soft tissue repair.

Decellularized extracellular matrix (dECM)–based biomaterials are of great clinical utility in soft tissue repair applications due to their regenerative properties. Multi-layered dECM devices have been developed for clinical indications where additional thickness and biomechanical performance are required. However, traditional approaches to the fabrication of multi-layered dECM devices introduce additional laminating materials or chemical modifications of the dECM that may impair the biological functionality of the material. Using an established dECM biomaterial, ovine forestomach matrix, a novel method for the fabrication of multi-layered dECM constructs has been developed, where layers are bonded via a physical interlocking process without the need for additional bonding materials or detrimental chemical modification of the dECM. The versatility of the interlocking process has been demonstrated by incorporating a layer of hyaluronic acid to create a composite material with additional biological functionality. Interlocked composite devices including hyaluronic acid showed improved in vitro bioactivity and moisture retention properties.

Retrospective real-world comparative effectiveness of ovine forestomach matrix and collagen/ORC in the treatment of diabetic foot ulcers.

The retrospective pragmatic real‐world data (RWD) study compared the healing outcomes of diabetic foot ulcers (DFUs) treated with either ovine forestomach matrix (OFM) (n = 1150) or collagen/oxidised regenerated cellulose (ORC) (n = 1072) in out‐patient wound care centres. Median time to wound closure was significantly (P = .0015) faster in the OFM group (14.6 ± 0.5 weeks) relative to the collagen/ORC group (16.4 ± 0.7). A sub‐group analysis was performed to understand the relative efficacy in DFUs requiring longer periods of treatment and showed that DFUs treated with OFM healed up to 5.3 weeks faster in these challenging wounds. The percentage of wounds closed at 36 weeks was significantly improved in OFM treated DFUs relative to the collagen/ORC. A Cox proportional hazards analysis showed OFM‐treated wounds had a 18% greater probability of healing versus wounds managed with collagen/ORC, and the probability increased to 21% when the analysis was adjusted for multiple variables. This study represents the first large retrospective RWD analysis comparing OFM and collagen/ORC and supports the clinical efficacy of OFM in the treatment of DFUs.

Extracellular matrix graft for reconstruction over exposed structures: a pilot case series.

Soft tissue defects, especially those involving exposed vital structures, present a reconstructive challenge because poor vascularity of such defects typically makes immediate skin grafting unviable. Where flap procedures are inappropriate or not possible, dermal matrices represent an alternative reconstructive option for defects with denuded vital structures. With dermal matrices becoming increasingly available and technologically advanced, we evaluated an ovine-derived extracellular matrix graft in the reconstruction of complex soft tissue defects involving exposed vital structures. Six cases of soft tissue defects exhibiting denuded vital structures underwent reconstruction using an ovine forestomach matrix graft as a dermal matrix. Grafts were fixed directly into defects for immediate coverage and subsequently temporised defects via granulation tissue formation for later skin graft or secondary closure. Defect granulation and epithelialisation were monitored until closure and the final aesthetic and functional outcomes were evaluated. Complete healing was achieved in all cases, with defect granulation becoming observable within one to two weeks and complete granulation occurring within one to six weeks. Granulation tissue resulting from the graft was suitable for skin grafting, with 100% take of skin grafts after one week and complete re-epithelialisation in two to three weeks in the four cases that received a skin graft. Good cosmetic, functional and patient satisfaction outcomes were achieved in all cases. The present series demonstrates our initial use of an extracellular matrix-based dermal matrix in reconstructing defects with exposed vital structures. While such dermal matrices do not supersede or replace flap procedures, they represent an alternative option on the reconstructive ladder in cases where flap procedures are not appropriate or possible.

Extracellular matrix graft for the surgical management of Hurley stage III hidradenitis suppurativa: a pilot case series.

Surgical management of Hurley stage III hidradenitis suppurativa (HS) typically involves the excision of diseased tissue and subsequent reconstruction, potentially leading to complications or recurrence of the disease. This pilot case series sought to evaluate a decellularised ovine forestomach matrix (OFM) extracellular matrix (ECM) graft for soft tissue regeneration as part of surgical reconstruction of stage III HS of the axilla. The prospective pilot case series involved six participants and a total of eight defects. The ECM graft was used either as a dermal substitute for a staged reconstruction (n=3 defects) or as an implant under a fasciocutaneous flap (n=5 defects) following wide excision of the diseased tissue. In all cases complete healing was achieved, with no major surgical complications. When used as a dermal substitute the OFM graft was completely granulated within 2-4 weeks, with defects closing by secondary intention or following placement of a split-thickness skin graft. When used as an implant beneath a fasciocutaneous flap, healing of the surgical sites was observed after 1-3 months. At the long-term follow-up (3-12 months), all participants had excellent range of motion and none had reported disease recurrences. This pilot case series explored the implementation of an ECM graft as part of the surgical management of axilla Hurley stage III HS. Although the study had a limited number of participants, long-term outcomes were promising and suggest further studies are warranted.

A novel chemotactic factor derived from the extracellular matrix protein decorin recruits mesenchymal stromal cells in vitro and in vivo.

Soft tissue is composed of cells surrounded by an extracellular matrix that is made up of a diverse array of intricately organized proteins. These distinct components work in concert to maintain homeostasis and respond to tissue damage. During tissue repair, extracellular matrix proteins and their degradation products are known to influence physiological processes such as angiogenesis and inflammation. In this study we developed a discovery platform using a decellularized extracellular matrix biomaterial to identify new chemotrophic factors derived from the extracellular matrix. An in vitro culture of RAW.264 macrophage cells with the biomaterial ovine forestomach matrix led to the identification of a novel ~12 kDa chemotactic factor, termed ‘MayDay’, derived from the N-terminal 31–188 sequence of decorin. The recombinant MayDay protein was shown to be a chemotactic agent for mesenchymal stromal cells in vitro and in vivo. We hypothesize that the macrophage-induced cleavage of decorin, via MMP-12, leads to the release of the chemotactic molecule MayDay, that in turn recruits cells to the site of damaged tissue.

Prospective Multicenter Evaluation of an Advanced Extracellular Matrix for Wound Management.

To evaluate an advanced extracellular matrix made of ovine forestomach matrix (OFM) for healing a variety of wound types. Participants were enrolled from inpatient, outpatient, and home healthcare settings. The OFM was used to treat all wounds and applied to the wound bed every 3 to 7 days until closure. Researchers enrolled 29 participants with 33 wounds. Average time to wound closure was 8.2 weeks, the percentage of wounds that reduced in size by 50% or more at 4 weeks was 64%, the average wound area reduction at 4 weeks was 66%, and 73% of wounds had closed at 12 weeks. No adverse effects were observed. This represents the first Canadian evaluation of OFM for the treatment of wounds, and the positive healing outcomes observed could support more widespread adoption of this matrix.

Functional Insights from the Proteomic Inventory of Ovine Forestomach Matrix.

Ovine forestomach matrix (OFM) is a decellularized extracellular matrix (dECM) biomaterial that serves as a scaffold for remodeling damaged soft tissue. dECM biomaterials are used in a variety of clinical applications, and their regenerative capacity is encoded not only in their biophysical properties but also in their molecular diversity. In this study, the proteome of OFM was characterized via both targeted and global mass spectrometry (MS) with the use of heavy isotope labeled (SIL) internal standards. Proteins were identified following either chemical digestion or extraction using saline or guanidine hydrochloride, followed by high resolution size exclusion chromatography. Identified proteins were annotated using the matrisome database and molecular function using the gene ontology database. The characterization identified 153 unique matrisome proteins, including 25 collagens, 58 glycoproteins, 12 proteoglycans, 13 ECM affiliated proteins, 20 ECM regulators, and 23 secreted factors. This inventory represents a comprehensive array of matrix proteins that are retained in OFM after processing. The diversity of proteins identified may contribute to OFM's remodeling capacity in clinical applications.

Ionic silver functionalized ovine forestomach matrix \u2013 a non-cytotoxic antimicrobial biomaterial for tissue regeneration applications

BackgroundAntimicrobial technologies, including silver-containing medical devices, are increasingly utilized in clinical regimens to mitigate risks of microbial colonization. Silver-functionalized resorbable biomaterials for use in wound management and tissue regeneration applications have a narrow therapeutic index where antimicrobial effectiveness may be outweighed by adverse cytotoxicity. We examined the effects of ionic silver functionalization of an extracellular matrix (ECM) biomaterial derived from ovine forestomach (OFM-Ag) in terms of material properties, antimicrobial effectiveness and cytotoxicity profile.MethodsMaterial properties of OFM-Ag were assessed by via biochemical analysis, microscopy, atomic absorption spectroscopy (AAS) and differential scanning calorimetry. The silver release profile of OFM-Ag was profiled by AAS and antimicrobial effectiveness testing utilized to determine the minimum effective concentration of silver in OFM-Ag in addition to the antimicrobial spectrum and wear time. Biofilm prevention properties of OFM-Ag in comparison to silver containing collagen dressing materials was quantified via in vitro crystal violet assay using a polymicrobial model. Toxicity of ionic silver, OFM-Ag and silver containing collagen dressing materials was assessed toward mammalian fibroblasts using elution cytoxicity testing.ResultsOFM-Ag retained the native ECM compositional and structural characteristic of non-silver functionalized ECM material while imparting broad spectrum antimicrobial effectiveness toward 11 clinically relevant microbial species including fungi and drug resistant strains, maintaining effectiveness over a wear time duration of 7-days. OFM-Ag demonstrated significant prevention of polymicrobial biofilm formation compared to non-antimicrobial and silver-containing collagen dressing materials. Where silver-containing collagen dressing materials exhibited cytotoxic effects toward mammalian fibroblasts, OFM-Ag was determined to be non-cytotoxic, silver elution studies indicated sustained retention of silver in OFM-Ag as a possible mechanism for the attenuated cytotoxicity.ConclusionsThis work demonstrates ECM biomaterials may be functionalized with silver to favourably shift the balance between detrimental cytotoxic potential and beneficial antimicrobial effects, while preserving the ECM structure and function of utility in tissue regeneration applications.

Semitransparent bandages based on chitosan and extracellular matrix for photochemical tissue bonding

BackgroundExtracellular matrices (ECMs) are often used in reconstructive surgery to enhance tissue regeneration and remodeling. Sutures and staples are currently used to fix ECMs to tissue although they can be invasive devices. Other sutureless and less invasive techniques, such as photochemical tissue bonding, cannot be coupled to ECMs because of their intrinsic opacity to light.ResultsWe succeeded in fabricating a biocompatible and adhesive device that is based on ovine forestomach matrix (OFM) and a chitosan adhesive. The natural opacity of the OFM has been overcome by adding the adhesive into the matrix that allows for the light to effectively penetrate through it. The OFM-chitosan device is semitransparent (attenuation length ~ 106 µm) and can be photoactivated by green light to bond to tissue. This device does not require sutures or staples and guarantees a bonding strength of ~ 23 kPa.ConclusionsA new semitransparent and biocompatible bandage has been successfully fabricated and characterized for sutureless tissue bonding.

Collagen Fibril Response to Strain in Scaffolds from Ovine Forestomach for Tissue Engineering.

Scaffold biomaterials are typically applied surgically as reinforcement for weakened or damaged tissue, acting as substrates on which healing tissue can grow. Natural extracellular matrix (ECM) materials consisting mainly of collagen are often used for this purpose, but are anisotropic. Ovine forestomach matrix (OFM) ECM was exposed to increasing strain and synchrotron-based SAXS diffraction patterns and revealed that the collagen fibrils within underwent changes in orientation, orientation index (a measure of isotropy), and extension. Response to the strain depended on the direction the collagen fibrils were oriented. When the ECM was stretched in the direction of collagen fibril orientation, the fibrils become more oriented and begin to take up the strain immediately (as shown by the increased d-spacing). Stretch applied perpendicular to dominant fibril direction caused the fibrils to initially become less oriented as they were pulled away from the original direction, and less force was initially transmitted along the length of the fibrils (i.e., the d-spacing changed less). SAXS analysis of OFM and the starting raw tissue showed there is no difference in the structural arrangement of the collagen fibrils. Understanding the directional structural response of these materials under strain may influence how surgeons select and place the materials in use.

A novel native collagen dressing with advantageous properties to promote physiological wound healing.

Chronic hard-to-heal wounds generate high costs and resource use in western health systems and are the focus of intense efforts to improve healing outcomes. Here, we introduce a novel native collagen (90 %):alginate (10 %) wound dressing and compare it with the established oxidised dressings Method: Matrices were analysed by atomic force microscopy (AMF), scanning electron microscopy (SEM), and immunoelectron microscopy for collagen types I, III and V. Viability assays were performed with NIH-3T3 fibroblasts. Matrix metalloproteinase (MMP) binding was analysed, and the effect of the wound dressings on platelet-derived growth factor B homodimer (PDGF-BB) was investigated. Unlike oxidised regenerated cellulose (ORC)/collagen matrix and ovine forestomach matrix (OFM), the three-dimensional structure of the native collagen matrix (NCM) was found to be analogous to intact, native, dermal collagen. Fibroblasts seeded on the NCM showed exponential growth whereas in ORC/collagen matrix or OFM, very low rates of proliferation were observed after 7 days. MMP sequestration was effective and significant in the NCM. In addition, the NCM was able to significantly stabilise PDGF-BB in vitro. We hypothesise that the observed microstructure of the NCM allows for an effective binding of MMPs and a stabilisation and protection of growth factors and also promotes the ingrowth of dermal fibroblasts, potentially supporting the re commencement of healing in previously recalcitrant wounds. This work was supported by BSN Medical, Hamburg, Germany.

Treatment of ulcerated necrobiosis lipoidica with ovine forestomach matrix

Necrobiosis lipoidica (NL) results from degradation of the collagen extracellular matrix; these recurring ulcerated lesions are an especially challenging condition to treat. Ovine forestomach matrix (OFM) is a decellularised extracellular matrix and was used to successfully close a pretibial ulcer resulting from NL. Complete closure of the wound was achieved in 22 weeks, after four applications of OFM. This suggests OFM may be considered for the treatment of these challenging wounds.

EVALUATION OF SCAFFOLDS IN VITRO FOR USE IN TENDON REGENERATION

IntroductionInjuries to tendons can cause major morbidity in healthy, young active people as well as in the increasing aged population. Providing a scaffold that encourages appropriate cell attachment, growth, and...

Clinical Outcomes Following the Use of Ovine Forestomach Matrix (Endoform Dermal Template) to Treat Chronic Wounds

The suitability of the ovine forestomach matrix (OFM) for the treatment of recalcitrant wounds was evaluated in 19 patients. At 12 weeks, 50% of wounds had closed, and the average reduction in surface area was 73.4%. Promising outcomes of this initial series support the clinical consideration of OFM.