Porcine Small Intestinal Submucosa Research Articles

Exosomes from hypoxic urine-derived stem cells facilitate healing of diabetic wound by targeting SERPINE1 through miR-486-5p

Vascular pathologies and injuries are important factors for the delayed wound healing in diabetes. Previous studies have demonstrated that hypoxic environments could induce formation of new blood vessels by regulating intercellular communication and cellular behaviors. In this study, we have enhanced the angiogenic potential of exosomes by subjecting urine-derived stem cells (USCs) to hypoxic preconditioning. To prolong the retention of exosomes at the wound site, we have also engineered a novel dECM hydrogel termed SISMA, which was modified from porcine small intestinal submucosa (SIS). For its rapid and controllable gelation kinetics, excellent biocompatibility, and exosome release capability, the SISMA hydrogel has proven to be a reliable delivery vehicle for exosomes. The hypoxia-induced exosomes-loaded hydrogel has promoted endothelial cell proliferation, migration, and tube formation. More importantly, as evidenced by significant in vivo vascular regeneration in the early stages post-injury, it has facilitated tissue repair. This may because miR-486–5p in H-exo inhibit SERPINE1 activity in endothelial cell. Additionally, miRNA sequencing analysis suggested that the underlying mechanism for enhanced angiogenesis may be associated with the activation of classical HIF-1α signaling pathway. In summary, our study has presented a novel non-invasive, cell-free therapeutic approach for accelerating diabetes wound healing and development of a practical and efficient exosomes delivery platform.

Reconstruction of deep and perforating corneal defects in dogs-A review (Part II/III): Biomaterials and keratoprosthesis.

The surgical reconstruction of severe corneal ulcers is a common and crucial component of the clinical practice of veterinary ophthalmology. Numerous surgical techniques are used in dogs for corneal reconstruction, and these techniques may be categorized by the material used to repair the corneal lesion. The first part of the present review described procedures that utilize autogenous ocular tissues, homologous donor tissues, and heterologous donor tissues. In this second part of the review, the categories of biomaterials and keratoprosthetics will be summarized. Biomaterials that are reported for use in dogs include amniotic membrane, porcine urinary bladder acellular matrix, porcine small intestinal submucosa, acellular porcine corneal stroma, and other miscellaneous soft tissue and cartilage grafts (e.g., preserved equine renal capsule, autologous omentum, autologous buccal mucosa membrane, bovine pericardium, and homologous peritoneum). Descriptions of keratoprosthesis surgery in dogs are currently limited, but the use of artificial corneal transplants hold promise for dogs with severe, vision-compromising corneal disease that is not amenable to other reconstruction techniques. This review describes the results of experimental studies evaluating these graft materials in dogs, and it will summarize the findings and outcomes of the clinical articles published in each material category. Reporting inconsistencies and areas where additional research is required will be highlighted to help guide future studies in this area. A major aim of this review is to help identify potential subjects that could be evaluated in future investigations and that might lead to refinements in clinical practice.

Comparison of porcine small intestinal submucosa and autologous graft material for repairing tympanic membrane perforation: a systematic review and meta-analysis.

To perform a systematic review and meta-analysis exploring the effectiveness of porcine small intestinal submucosa(pSIS) compared with autologous grafts for tympanic membrane perforation repair. A prospective meta-analysis protocol was registered on PROSPERO (International Prospective Register of Systematic Reviews) on June 5th, 2024, under protocol CRD42024551979. PubMed, Embase/Ovid and Cochrane Central databases were searched from inception to 28/05/2024 for studies comparing the use of pSIS versus autologous grafts (perichondrium, cartilage, temporalis fascia or cartilage-perichondrium) for tympanic membrane perforation repair. The outcomes evaluated were persistent perforation after surgery, operative time and hearing outcome. Statistical analyses were performed using the online Review Manager (Cochrane Collaboration). A subgroup analyses were carried out for the paediatric population. We included 1,407 patients (1447 ears) from seven records; six retrospective cohort studies and one randomised controlled trial (RCT). pSIS graft was used in 563 ear surgeries (38.1%). Four studies included children with a mean age ranging from 7.3 to 11.7 years and the other 3 studies included adults with a mean age ranging from 30.8 to 48.4 years. Follow-up ranged from 2 to 132 months. There was no statistically significant difference in the failure rate (persistent perforation) between pSIS graft and autologous graft (RR 0.95; 95% CI 0.67-1.33; p = 0.76). However, reduced operative time was associated with using pSIS grafts (MD -16.12min; 95% CI -22.94-9.31; p = < 0.00001). Tympanic membrane perforation repair with pSIS grafts had a similar failure rate and hearing outcome compared to autologous grafts and demonstrated an association with reduced operative time.

Computational Model for Early-Stage Aortic Valve Calcification Shows Hemodynamic Biomarkers.

Heart disease is a leading cause of mortality, with calcific aortic valve disease (CAVD) being the most prevalent subset. Being able to predict this disease in its early stages is important for monitoring patients before they need aortic valve replacement surgery. Thus, this study explored hydrodynamic, mechanical, and hemodynamic differences in healthy and very mildly calcified porcine small intestinal submucosa (PSIS) bioscaffold valves to determine any notable parameters between groups that could, possibly, be used for disease tracking purposes. Three valve groups were tested: raw PSIS as a control and two calcified groups that were seeded with human valvular interstitial and endothelial cells (VICs/VECs) and cultivated in calcifying media. These two calcified groups were cultured in either static or bioreactor-induced oscillatory flow conditions. Hydrodynamic assessments showed metrics were below thresholds associated for even mild calcification. Young's modulus, however, was significantly higher in calcified valves when compared to raw PSIS, indicating the morphological changes to the tissue structure. Fluid-structure interaction (FSI) simulations agreed well with hydrodynamic results and, most notably, showed a significant increase in time-averaged wall shear stress (TAWSS) between raw and calcified groups. We conclude that tracking hemodynamics may be a viable biomarker for early-stage CAVD tracking.

Improved Composite Hydrogel for Bioengineered Tracheal Graft Demonstrates Effective Early Angiogenesis.

Background/Objectives: Collagen-agarose hydrogel blends currently used in tracheal graft bioengineering contain relatively high concentrations of collagen to withstand mechanical stresses associated with native trachea function (e.g., breathing). Unfortunately, the high collagen content restricts effective cell infiltration into the hydrogel. In this study, we created an improved hydrogel blend with lower concentrations of collagen (<5 mg/mL) and characterized its capacity for fibroblast invasion and angiogenesis. Methods: Four collagen-agarose hydrogel blends were created: 1 mg/mL type 1 collagen (T1C) and 0.25% agarose, 1 mg/mL T1C and 0.125% agarose, 2 mg/mL T1C and 0.25% agarose, and 2 mg/mL T1C and 0.125% agarose. The hydrogel surface was seeded with fibroblasts, while both endothelial cells and fibroblasts (3:1 ratio) were mixed within the hydrogel matrix. We assessed early angiogenesis by observing fibroblast migration and endothelial cell morphology (elongation and branching) at 7 days. In addition, we performed immunostaining for alpha-smooth muscle actin (aSMA) and explored the gene expression of various angiogenic markers (including vascular endothelial growth factor; VEGF). Results: Gels with lower agarose concentrations (0.125%) with 1 or 2 mg/mL T1C were more effective in allowing early attachment and migration of surface-applied fibroblasts compared to gels with higher (0.25%) agarose concentrations. The low-agarose gels also allowed cells to quickly adopt a spread morphology and self-assemble into elongated structures indicative of early angiogenesis, while demonstrating positive immunostaining for aSMA and increased gene expression of VEGF by day 7. Conclusions: Hydrogel blends with collagen and low agarose concentrations may be effective in allowing early cellular infiltration and angiogenesis, making such gels a suitable cell substrate for use in the development of composite bioengineered tracheal grafts. The collagen-agarose hydrogel blend is meant to be cast around a three-dimensional (3D) printed polycaprolactone support structure and wrapped in porcine small intestine submucosa ECM to create an off-the-shelf bioengineered tracheal implant.

Accelerated cartilage regeneration through immunomodulation and enhanced chondrogenesis by an extracellular matrix hydrogel encapsulating Kartogenin

Articular cartilage is crucial for the functional integrity of joints yet vulnerable to a spectrum of injuries. The adverse immune microenvironment ensuing from injury, coupled with the intrinsic property of the tissue characterized by limited cellularity, poses a significant challenge to the reconstruction of cartilage defect. In this study, an extracellular matrix hydrogel derived from porcine small intestinal submucosa (SIS) with encapsulation of Kartogenin (KGN) has been designed for the cartilage repair and regeneration. The SIS hydrogel, which possessed a three-dimensional porous structure akin to the natural cartilage, has provided a scaffold essential for the progenitor cells engaged in the repair process and sustained release of KGN. As shown by in vitro experiments, the KGN could recruit host endogenous bone marrow-derived mesenchymal stem cells (BMSCs) and induce them to differentiate into chondrocytes, thus enabling in situ cartilage regeneration without cell transplantation. Notably, the bioactive component of SIS was further revealed to possess excellent immunomodulatory capacity to induce the phenotypic shift from M1 to M2 macrophages, which could enhance the chondrogenic differentiation of BMSCs indirectly. Additionally, in vivo experiments showed that the regenerated tissues of the composite SIS hydrogel group were close to the natural hyaline cartilage. Leveraging the combined effects of KGN and SIS hydrogel, this innovative composite material shows great potential as a biomaterial for effective cartilage repair and regeneration.

A multicenter randomized controlled trial comparing short- and medium-term outcomes of novel biologics and lightweight synthetic mesh for laparoscopic inguinal hernia repair.

The use of biological graft in laparoscopic inguinal hernia repair (LIHR) has been controversial, and there is a lack of high-level evidence to confirm the value of biological graft in LIHR. The purpose of this study is to evaluate the effectiveness of a novel composite biologics in LIHR. A multicenter, single-blinded, randomized controlled clinical trial was designed. Fifty patients with unilateral primary inguinal hernia were randomly assigned to the experimental and control group (1:1). The experimental group was repaired with a non-crosslinked composite extracellular matrix from porcine urinary bladder matrix and small intestinal submucosa (UBM/SIS). The control group was repaired with a lightweight, large-pore, synthetic mesh. The primary endpoint was the effectiveness rate of hernia repair. The patients were followed up for four years. No significant difference was found between the experimental group and the control group in the effective rate of hernia repair (24/24[100%] vs 21/22[95.45%], RR, 0.4667; 95%CI, 0.3294-2.304; P = 0.4783). There was no fever, seroma, infection, groin pain, foreign body discomfort or recurrence in the experimental group during the follow-up. In the control group, there were 2 cases of seroma 14days after operation, 1 case of groin discomfort 60days after operation and one case of recurrence 410days after surgery. Compared with the lightweight synthetic mesh, the novel UBM/SIS graft has comparable short-term and medium-term effectiveness in LIHR, and the incidence of postoperative complications such as seroma groin discomfort is lower. Trial registration Clinical Trials Registry: ChiCTR1800020173.

Enhanced fibrocartilage regeneration at the tendon-bone interface injury through extracellular matrix hydrogel laden with bFGF-overexpressing human urine-derived stem cells

The tendon-bone interface (TBI) is crucial in the transfer of mechanical loads; however, it is susceptible to injuries that frequently result in healing via fibrous scar tissue formation. Consequently, regeneration of the fibrocartilaginous zone has become a pivotal area subject. At present, the use of stem cells represents a notably promising approach for TBI treatment. Especially, human urine-derived stem cells (hUSCs) present a practical option for cell-based therapies. Nevertheless, the chondrogenic differentiation potential of hUSCs is limited. To address this, basic fibroblast growth factor (bFGF) was transinfected into hUSCs to bolster their differentiation capacity and facilitate the formation of fibrocartilage in the target area. Additionally, the local immune microenvironment dramatically influences TBI healing, with macrophages playing a vital role. Effective healing relies on the phenotype transition of macrophages, with an imbalance often leading to insufficient regeneration and scar tissue formation. Innovations in biomaterials have provided new avenues for TBI repair, such as the porcine small intestinal submucosa (SIS) hydrogel developed in our prior research. In addition to serving as a carrier for stem cell delivery, the hydrogel’s bioactive components support tissue repair and immune regulation. In the present study, SIS hydrogel loaded with hUSCs that overexpress bFGF was used for the treatment of TBI injury, which is expected to correct inflammatory response imbalances, and promote macrophage polarization towards healing phenotypes, creating a favorable immune microenvironment. The combined effects of bFGF and the optimized immune setting are anticipated to enhance hUSCs’ chondrogenic potential, aiding in the functional restoration of TBI injuries.

One-Year Outcome of an Ongoing Pre-Clinical Growing Animal Model for a Tissue-Engineered Valved Pulmonary Conduit.

Objectives: A self-constructed valved pulmonary conduit made out of a de-cellularized porcine small intestinal submucosal extracellular matrix biological scaffold was tested in a chronic growing lamb model. Methods: The conduit was implanted in pulmonary valve position in 19 lambs. We monitored clinical, laboratory, and echocardiographic findings until 12 months after surgery. In two animals, euthanasia was planned at nine and twelve months. Pre-mortem chest computed tomography and post-mortem pathologic work up were performed. Data are presented as frequency and percentage, median and range, or mean and standard deviation. Results: Twelve (63.2%) animals survived the perioperative period. Three unexpected deaths occurred during the follow-up period: one due to aspiration pneumonia at 23 days after surgery, and two due to early and late infective endocarditis of the conduit at 18 and 256 days. In the two animals with planned scarification, the pre-mortem CT scan revealed mild or no calcification within the conduit or valve leaflets. In the echocardiographic examination at 12 months, peak and mean systolic pressure gradients across the conduit valve were 6.5 (3-21) mmHg and 3 (2-12) mmHg, while valve regurgitation was none (n = 2), trivial (n = 5), moderate (n = 1), or severe (n = 1). No clinical or laboratory signs of hemolysis were seen. After 12 months of follow-up, the animals' body weights had increased from 33 (27-38) kg to 53 (38-66) kg (p = 0.010). Conclusions: Implantation of a valved pulmonary conduit in our growing lamb model was feasible. Infective endocarditis of the implanted valved conduit remained a significant complication.

Therapeutic application of decellularized porcine small intestinal submucosa scaffold in conjunctiva reconstruction

The objective of this study was to investigate the biological feasibility and surgical applicability of decellularized porcine small intestinal submucosa (DSIS) in conjunctiva reconstruction. A total of 52 Balb/c mice were included in the study. We obtained the DSIS by decellularization, evaluated the physical and biological properties of DSIS in vitro, and further evaluated the effect of surgical transplantation of DSIS scaffold in vivo. The histopathology and ultrastructural analysis results showed that the scaffold retained the integrity of the fibrous morphology while removing cells. Biomechanical analysis showed that the elongation at break of the DSIS (239.00 ± 12.51%) were better than that of natural mouse conjunctiva (170.70 ± 9.41%, P < 0.05). Moreover, in vivo experiments confirmed the excellent biocompatibility of the decellularized scaffolds. In the DSIS group, partial epithelialization occurred at day-3 after operation, and the conjunctival injury healed at day-7, which was significantly faster than that in human amniotic membrane (AM) and sham surgery (SHAM) group (P < 0.05). The number and distribution of goblet cells of transplanted DSIS were significantly better than those of the AM and SHAM groups. Consequently, the DSIS scaffold shows excellent biological characteristics and surgical applicability in the mouse conjunctival defect model, and DSIS is expected to be an alternative scaffold for conjunctival reconstruction.

Hydrogel Derived from Decellularized Porcine Small Intestinal Submucosa as a Physical Shielding Repaired the Gut Epithelial Barrier of Murine Ulcerative Colitis

AbstractUlcerative colitis (UC) is associated with the shedding of the gut mucus. Decellularized porcine small intestinal submucosa (SIS‐ECM) contains numerous active forms of extracellular matrix as well as growth factors. Herein, a mucus‐mimetic hydrogel (MAG) is designed as a barrier therapy by integrating SIS‐ECM with hyaluronic acid and epigallocatechin‐3‐gallate. MAG not only presented the viscoelastic behaviors with G' of 4000 Pa but also good thixotropy. Moreover, MAG as a physical shielding is effective to hinder E. coli invasion. Besides, the good repairing effect on the injured Caco‐2 cells is presented by MAG. When MAG as a biomimetic mucus is rectally administrated to colitis mouse, it alleviated effectively the colitis symptoms and improved the colonic shorting. Moreover, expression of IL‐1β, IL‐6, and TNF‐α at the laminae propria is substantially inhibited by MAG. Besides, the colonic epitheliums are well rearranged, and the tight junction proteins (ZO‐1, Occludin‐1, Claudin‐5) between them are greatly upregulated after MAG treatment. Meanwhile, the mucus secretion of goblets cells is effectively repaired by MAG treatment. The repairing mechanism of intestinal mucosa barriers is associated with promoting the proliferation and differentiation of intestinal stem cells. Collectively, MAG might be a promising strategy of barrier therapy for UC.

Human umbilical cord mesenchymal stem cells combined with porcine small intestinal submucosa promote the healing of full-thickness skin injury in SD rats.

Aim: To assess the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with porcine small intestinal submucosa (SIS) on full-thickness skin injuries in rats. Methods: We established full-thickness skin injury models in Sprague-Dawley rats, dividing them into blank control, SIS, hUCMSCsand hUCMSCs combined with SIS. We monitored wound healing, scoresand area, and analyzed inflammatory cells, microvessel densityand collagen fibers after 12days. Results: The blank group showed no healing, forming a scar of 0.6×0.5cm2, while SIS and hUCMSCs groups exhibited incomplete healing with 0.4×0.5cm2 scabs. Wound healing was significantly better in the hUCMSCs combined with the SIS group. Conclusion: Local application of hUCMSCs combined with SIS enhances full-thickness skin injury wound healing in rats.

Use of Anal Fistula Plug for Treatment of Fistula-in-ano: A Novel Technique?

Abstract Background: Fistula-in-ano is a chronic phase of anorectal suppuration characterized by purulent discharge. The conventional gold standard fistulotomy opens the entire track to heal with secondary intention. Anal fistula plug (AFP) is one of the newer modalities where the track is debrided from within and plugged with a biodegradable material made of porcine small intestinal submucosa. Materials and Methods: A total of 100 patients were enrolled in a randomized prospective study into two groups: conventional fistulotomy (CF) group and AFP group with 50 patients in each arm. The demography and surgical outcomes were assessed for postoperative pain, discharge and recovery, and failure. Results: All 100 patients included in the study had a history of anorectal suppuration which led to the residual anal fistula. Postoperative pain and analgesic requirements were equal in the two groups. The recovery period and return to work were shorter in the AFP group, and this difference was statistically significant. The success rate was 100% in the CF group as compared to 76% in the AFP group. There was no significant complication, failure, or recurrence in the CF group as against allergy (1), extrusion of plug (2), and failure/recurrence (9) in the AFP group. Conclusion: Our study shows that the application of bioprosthetic plugs may be an alternative option in a select group of patients. AFP has also shown to have a faster recovery with less morbidity and comparable success rates.

Interlayer repair with porcine small intestinal submucosa versus internal repair with tragus cartilage in endoscopic tympanoplasty

ObjectiveEndoscopic tympanoplasty includes various surgical methods, such as internal repair, interlayer repair, and external overlay. This technique requires autologous materials, allografts, and xenografts, which are used to repair tympanic membrane (TM) perforation. To obtain good results, appropriate surgical methods and repair materials should be selected. This study aims to assess the efficacy of repairing refractory TM perforations in the porcine small intestinal submucosa (SIS) during transcanal endoscopic type I tympanoplasty. MethodA retrospective chart review was performed on patients who underwent TM perforation repair with porcine SIS and tragus cartilage between January 2022 and September 2022 at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. Perforation size, tympanic status, pre- and postoperative symptoms, follow-up data, wound healing rates, and hearing improvement were analysed. ResultsOf the 115 patients included in the study, 56 underwent interlayer repair with porcine SIS of the TM, and 59 patients underwent internal repair with tragus cartilage. No significant difference was found between the two groups at baseline in terms of age, sex, disease course, perforation side, tympanic status, underlying disease, or preoperative infection. The total postoperative effective rate of interlayer implantation with porcine SIS was 91.07% (51 patients), and that of internal implantation with tragus cartilage was 88.14% (52 patients). No significant difference was found in terms of the graft success rate between the two surgical methods (p = 0.887). Postoperative pure tone auditory (PTA) and air-bone gap (ABG) density significantly increased in both groups compared with before surgery (p < 0.05). However, the postoperative PTA and ABG density were not significantly different 3 months post-surgery between the two groups (p > 0.05). Compared to those in the internal implantation group, the patients in the interlayer group had a shorter operation duration (51.36 ± 6.76 min vs. 59.71 ± 7.45 min, t = 6.298, p < 0.001) and less blood loss (11.91 ± 2.61 mL vs. 15.27 ± 2.57 mL, t = 7.019, p < 0.001). ConclusionsOur study suggests that the porcine SIS, as well as the tragus cartilage, has a high success rate in repairing irreversible TM perforation. Endoscopic tympanoplasty via interlayer implantation with porcine SIS offers distinct advantages, including the absence of donor-site incision and scar formation, and ease of graft modification and manipulation.

A Tissue Engineered 3D Model of Cancer Cell Invasion for Human Head and Neck Squamous-Cell Carcinoma.

Head and neck squamous-cell carcinoma (HNSCC) is associated with aggressive local invasiveness, being a main reason for its poor prognosis. The exact mechanisms underlying the strong invasive abilities of HNSCC remain to be elucidated. Therefore, there is a need for in vitro models to study the interplay between cancer cells and normal adjacent tissue at the invasive tumor front. To generate oral mucosa tissue models (OMM), primary keratinocytes and fibroblasts from human oral mucosa were isolated and seeded onto a biological scaffold derived from porcine small intestinal submucosa with preserved mucosa. Thereafter, we tested different methods (single tumor cells, tumor cell spots, spheroids) to integrate the human cancer cell line FaDu to generate an invasive three-dimensional model of HNSCC. All models were subjected to morphological analysis by histology and immunohistochemistry. We successfully built OMM tissue models with high in vivo-in vitro correlation. The integration of FaDu cell spots and spheroids into the OMM failed. However, with the integration of single FaDu cells into the OMM, invasive tumor cell clusters developed. Between segments of regular epithelial differentiation of the OMM, these clusters showed a basal membrane penetration and lamina propria infiltration. Primary human fibroblasts and keratinocytes seeded onto a porcine carrier structure are suitable to build an OMM. The HNSCC model with integrated FaDu cells could enable subsequent investigations into cancer cell invasiveness.

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 (&lt;3 hours), while PCMP and PCMP-XT were significantly more durable (&gt;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.

Application of multi-layer porcine small intestinal submucosa for the reconstruction of deep corneal defects in cats.

This study documented the application of porcine small intestinal submucosa (SIS) as a stand-alone scaffold for treating deep corneal defects in cats. Medical records of 20 cats with deep stromal ulcers, perforations, or corneal sequestra that underwent surgical treatment with SIS grafts between 2021 and 2022 were retrospectively reviewed. Data on re-epithelialization time, corneal transparency score, and complications were collected to analyze the reconstruction of deep corneal defects after SIS biomaterial implantation. All cats were unilaterally affected. The corneal defects varied in size, with a median diameter of 8.3 mm (range: 3-15 mm). Re-epithelialization of the SIS graft was completed 16-32 days after surgery (median, 22.3 days). No, mild, or moderate corneal transparency was detected in 90% of the cases. Complications were observed in eight cases (40%), including aqueous leakage (10%), partial SIS malacia (25%), and persistent bullous keratopathy (5%). The follow-up period ranged 90-725 days, with a median duration of 255 days. The SIS graft was successfully applied as a single scaffold in 17 of 20 cases (85%). The results of this study suggest that the application of commercial SIS is an effective surgical technique for managing deep corneal defects in cats.

Composite Biosynthetic Graft for Repair of Long-Segment Tracheal Stenosis: A Pilot In Vivo and In Vitro Feasibility Study.

Pediatric patients who undergo surgery for long-segment congenital tracheal stenosis (LSCTS) have suboptimal outcomes and postsurgical complications. To address this, we propose a biosynthetic graft comprising (1) a porcine small intestinal submucosa extracellular matrix (SIS-ECM) patch for tracheal repair, and (2) a resorbable polymeric exostent for biomechanical support. The SIS-ECM patch was evaluated in vivo in an ovine trachea model over an 8 month period. Concurrently, the biosynthetic graft was evaluated in a benchtop lamb trachea model for biomechanical stability. In vivo results show that SIS-ECM performs better than bovine pericardium (control) by preventing granulation tissue/restenosis, restoring tracheal architecture, blood vessels, matrix components, pseudostratified columnar and stratified epithelium, ciliary structures, mucin production, and goblet cells. In vitro tests show that the biosynthetic graft can provide the desired axial and flexural stability, and biomechanical function approaching that of native trachea. These results encourage future studies to evaluate safety and efficacy, including biomechanics and collapse risk, biodegradation, and in vivo response enabling a stable long-term tracheal repair option for pediatric patients with LSCTS and other tracheal defects.

Viscoelastic Properties of Acellular Matrices of Porcine Esophageal Mucosa and Comparison with Acellular Matrices of Porcine Small Intestine Submucosa and Bovine Pericardium.

The aim of this study was to compare the viscoelastic properties of a decellularized mesh from the porcine esophagus, prepared by our group, with two commercial acellular tissues derived from porcine small intestine submucosa and bovine pericardium for use in medical devices. The tissues' viscoelastic properties were characterized by creep tests in tension, applying the load in the direction of the fibers or the transverse direction, and also by dynamic-shear mechanical tests between parallel plates or in tension at frequencies between 0.1 and 35 Hz. All the tests were performed in triplicate at a constant temperature of 37 °C immersed in distilled water. The tissues' surface and cross-sectional microstructure were observed by scanning electron microscopy (SEM) to characterize the orientation of the fibers. The matrices of the porcine esophagus present an elastic modulus in the order of 60 MPa when loaded in the longitudinal direction while those of the porcine intestine submucosa and bovine pericardium have an elastic modulus below 5 MPa. Nevertheless, the shear modulus of bovine pericardium nearly triplicates that of the esophageal matrix. The viscoelasticity of decellularized esophageal mucosa is characterized by a fast change in the creep compliance with time. The slope of the creep curve in the double logarithmic plot is twice that of the control samples. These results are consistent with the microstructure observed under electron microscopy regarding the orientation of the fibers that make up the matrices.

A pleiotropic SIS-based hydrogel with immunomodulation via NLRP3 inflammasome inhibition for diabetic bone regeneration

As a progressive inflammatory disease, diabetes mellitus significantly changes the immuno-microenvironment, causing an elevation in M1 macrophages and inflammatory mediators. This inflammation condition possesses a negative impact on the cellular function of osteoblasts and vascular endothelial cells, resulting in impaired bone defect repair involving both angiogenesis and osteogenesis. In our study, a good biocompatible hydrogel, GB@SIS, was successfully fabricated for bone repair under diabetic conditions. This hydrogel consists of a porcine small intestinal submucosal (SIS) extracellular matrix with thermosensitivity, bionic structure, and pro-angiogenic properties, and BMP-4 loaded on graphene oxide (GO) can be sustainably released from the hydrogel. In vitro studies have shown that the composite hydrogel possesses a good ability to promote angiogenesis and enhance osteogenesis. Additionally, the hydrogel was also able to promote macrophage conversion from M1 to M2 macrophages, which subsequently results in the release of osteogenesis-related factors, specifically BMP-2. In a diabetic rat model with critical-size cranial defects, the GB@SIS hydrogel modulates the inflammatory microenvironment and significantly accelerates the process of bone repair. Subsequent investigations have revealed that the GB@SIS hydrogel exerts immunomodulatory effects via the suppression of the NLRP3 signaling pathway and the elevation of adhesion-related protein expression. In conclusion, the GB@SIS hydrogel demonstrates promising osteogenic characteristics as a biomaterial, exhibiting bone immunomodulatory properties that hold potential for its application in bone regeneration therapy specifically for diabetic patients.