Small Intestinal Submucosa Research Articles

Outcomes following tympanoplasty surgery using porcine-derived small intestinal submucosa.

To determine the outcomes of tympanoplasty surgery using porcine-derived small intestinal submucosa. A retrospective audit was conducted in a hospital setting. Thirty-five adult and paediatric patients who received a small intestinal submucosa graft as part of tympanoplasty surgery were retrospectively reviewed. Patients underwent either simple tympanoplasty (n = 26) or complex tympanoplasty as part of a concurrent otological procedure such as atticotomy and mastoidectomy. The main outcome measures were rate of tympanic membrane closure and change in four-frequency mean air-bone gap. Thirty-one patients had a follow-up period of longer than two months. Closure was obtained in 22 patients (71 per cent). The mean air-bone gap improved from 20.7 to 12.3 dB HL in the simple tympanoplasty group and from 22.3 to 12 dB HL in the complex tympanoplasty group. Tympanoplasty surgery with small intestinal submucosa is a viable option for patients where autologous graft is not available or in order to minimise donor site morbidity.

Abstract 10751: Pericardial Injection of Micronized Matrix Biomaterial Improves Post-Infarct Cardiac Function and Modulates Fibroblast Activity to Enhance Repair

Introduction: Injection of micronized biomaterials into the pericardial space leverages bioinductive properties to enhance post-infarct cardiac repair. This less invasive, potentially bedside, approach enables early intervention. Micronized porcine small intestinal submucosal extracellular matrix (SIS-ECM) contains fibroblast growth factor 2 (FGF2) which reduce fibrosis and increase vasculogenesis. Hypothesis: Pericardial delivery of micronized SIS-ECM improves post-infarct cardiac function. It promotes a proangiogenic and antifibrotic fibroblast phenotype. Methods: Mice received coronary ligation (infarct) through an undisrupted pericardium followed by pericardial delivery of micronized SIS-ECM or saline control. Pressure-volume loops were at 28 days. Myocardial isolectin stain assessed small vessel density on confocal microscopy. Mouse 3T3 cell line fibroblasts in 3D collagen matrices were exposed to biomaterial-conditioned media or media control. Multiplex analyzed paracrine activity. Collagen gel contraction and MMP2 production assessed profibrotic phenotype. FGF2 inhibitor elucidated mechanism. Results: Mice receiving micronized SIS-ECM had lower ventricular stiffness (0.23±0.03 vs 0.39±0.05 mmHg/uL; p=0.01), higher ejection fraction (34.7±2.5 vs 26.9±2.8%; p<0.05) and higher stroke work (1510±138 vs 1066±152 μL/mmHg; p=0.04). The SIS-ECM group had higher normalized border zone isolectin mean fluorescence (0.82±0.04 vs 0.58±0.06; p=0.01). Micronized SIS-ECM attenuated collagen gel contraction (26±6 vs 56±5%; p=0.01) and MMP2 release (66±2 vs 83±3 ng/mL; p<0.01). Micronized SIS-ECM increased fibroblast VEGF production (904±79 vs 628±25; pg/mL). FGF2 inhibitor negated biomaterial effects, increasing gel contraction (27.3±5.3 vs 11.0±0.5%; p=0.04; inhibitor vs no inhibitor) and MMP-2 release (141±8 vs 100±6 ng/mL; p=0.02). Conclusions: Pericardial injection of micronized SIS-ECM attenuates profibrotic fibroblast activity, increases release of angiogenic VEGF protein, increases vasculogenesis on isolectin staining, and preserves post-infarct cardiac function. This less invasive strategy facilitates early intervention to attenuate maladaptive post-infarct structural remodeling.

Evaluating tissue-engineered repair material for pelvic floor dysfunction: a comparison of in vivo response to meshes implanted in rats.

Achieving better anatomic restoration and decreasing the associated complications are necessary for material repair of pelvic floor dysfunction (PFD). This studywas aimed to investigate host response to tissue-engineered repair material (TERM) in rat models by comparing different materials and study the changes in biomechanical properties over time. TERM was constructed by seeding adipose-derived stem cells (ADSCs) on electrospun poly(L-lactide)-trimethylene carbonate-glycolide (PLTG) terpolymers. The TERM, PLTG, porcine small intestine submucosa mesh (SIS), and polypropylene (PP) (n = 6/group per time point) were implanted in rats for 7, 30, 60, and 90days. Hematoxylin-eosin and Masson's trichrome staining were used to assess the host response, and mechanical testing was used to evaluate the changes in biomechanical properties. In vivo imaging showed that the ADSCs were confined to the abdominal wall and did not migrate to other organs or tissues. The TERM was encapsulated by a thicker layer of connective tissue and was associated with less reduced inflammatory scores compared with PLTG and PP over time. The vascularization of the TERM was greater than that with PP and PLTG over time (p < 0.05) and was greater than that with SIS on day 90. The ultimate tensile strain and Young's modulus of the PP group showed the greatest increases, and the TERM group followed on day 90. This TERM achieved better host integration in rat models and better biomechanical properties, and it may be an alternative material for PFD.

Membranous Extracellular Matrix-Based Scaffolds for Skin Wound Healing.

Membranous extracellular matrix (ECM)-based scaffolds are one of the most promising biomaterials for skin wound healing, some of which, such as acellular dermal matrix, small intestinal submucosa, and amniotic membrane, have been clinically applied to treat chronic wounds with acceptable outcomes. Nevertheless, the wide clinical applications are always hindered by the poor mechanical properties, the uncontrollable degradation, and other factors after implantation. To highlight the feasible strategies to overcome the limitations, in this review, we first outline the current clinical use of traditional membranous ECM scaffolds for skin wound healing and briefly introduce the possible repair mechanisms; then, we discuss their potential limitations and further summarize recent advances in the scaffold modification and fabrication technologies that have been applied to engineer new ECM-based membranes. With the development of scaffold modification approaches, nanotechnology and material manufacturing techniques, various types of advanced ECM-based membranes have been reported in the literature. Importantly, they possess much better properties for skin wound healing, and would become promising candidates for future clinical translation.

Use of Polyvinyl Alcohol-Porcine Small Intestine Submucosa Stent in the Prevention of Anastomotic Leaks in the Porcine Colon

Use of Polyvinyl Alcohol-Porcine Small Intestine Submucosa Stent in the Prevention of Anastomotic Leaks in the Porcine Colon

Prevention of bleeding after percutaneous biopsy with a small intestinal submucosa hemostatic plug

Percutaneous biopsies (PBs) are the gold standard diagnostic procedures indicated for renal and hepatic disorders. Nevertheless, they can cause hemorrhages and are contraindicated for coagulopathic patients. In this study we designed, fabricated, and evaluated a small intestinal submucosa (SIS) plug to reduce, and potentially cease, bleeding to decrease death risk after percutaneous hepatic and renal biopsies in healthy and coagulopathic in vivo models. First, the plug's blocking capacity was determined with an increase in its diameter of 24 ± 11% after immersion in human blood, and the capacity to induce clotting on its surface. The plug's in vivo performance was evaluated in a healthy porcine model, which showed minimal inflammatory reaction without side effects confirmed by histological results after 30 days. The plug's response in the coagulopathic model was assessed using heparinized swine for 2 days, which revealed localized microhemorrhages and mild inflammatory response without any lesions to the surrounding tissue. No major adverse events nor macroscopic hemorrhages were detected in the animal models. Furthermore, we assessed the plug's efficacy to reduce and stop bleeding using a transplant-discarded human liver model (n = 14). In this case, the mass of blood lost was 43.8 ± 21.8% lower in plugged transplant-discarded human liver biopsies compared to control biopsies without a plug. The bleeding was stopped within three minutes in 92% of plugged cases, but only in 8% of non-plugged cases. We demonstrated the feasibility of making a hemostatic SIS plug, which does not induce major inflammatory reaction and can effectively reduce and stop bleeding after PBs in non-coagulopathic and coagulopathic in vivo models, and in a transplant-discarded human liver model. Statement of significancePercutaneous biopsy (PB) is a gold standard diagnostic procedure, but it can provoke life-threatening complications and is contraindicated for patients with coagulopathic disorders. This study demonstrates that small intestinal submucosa (SIS) can be manufactured into a biocompatible thrombogenic plug, insertable through a commercial Tru-Cut needle sheath. This device takes advantage of the collagen-rich composition of SIS to stop and reduce bleeding more effectively than the traditional PB, indicating that it could be routinely employed in a traditional biopsy to increase safety, or as a cost and time-reducing alternative to transjugular biopsy for coagulopathic patients.

Cervicovaginal reconstruction with small intestinal submucosa graft in congenital cervicovaginal atresia: A report of 38 cases

ObjectiveTo evaluate the quality of life and surgical outcomes in patients with congenital cervicovaginal malformation after cervicovaginal reconstruction. Study designThirty-eight patients diagnosed with congenital cervicovaginal aplasia and underwent cervicovaginal reconstruction using acellular porcine small intestinal submucosa (SIS) grafts were included in the study from January 2012 to December 2019. Of these, twenty-one patients underwent conventional laparoscopy, nine underwent robotic surgery, and eight underwent laparoendoscopic single-site (LESS) surgery. Clinical characteristics, perioperative data, condition of the neovagina and neocevix, post-operation complications, body image, resumption of menstruation, sexual function, and quality of life were assessed. ResultsThe average age of the patients was 16.4 ± 5.78 years. The operative procedure lasted 182.29 ± 70.85 min, with a hemoglobin decrease of 12.53 ± 7.55 g/dl. All surgery was completed successfully without complications. The total cost was highest in the robotic surgery group (P < 0.001). The cosmetic scores were significantly higher in the LESS group (P < 0.001). At a median follow-up of 49.79 ± 31.02 months, all patients resumed menstruation, except one patient who underwent hysterectomy due to vaginal obstruction. The average length of neovagina was 8.11 ± 0.75 cm, and the length of the cervix was 1.73 ± 1.00 cm. There were one patient with vaginal stenosis, two patients with cervical occlusion, two patients with cervical stenosis, and six patients with intrauterine device loss. Fourteen patients experienced sexual activity, with the total female sexual function index scores of 26.83 ± 3.49. Six patients had a desire of pregnancy, and one patient had pregnant via assisted-reproduction techniques. No differences in the mean physical component score (PCS) and mental component score (MCS) were identified among three different groups at baseline and all post-surgery time points (P > 0.05), but with the extension of follow-up, both PCS and MCS increased significantly in all groups (P < 0.001). ConclusionCervicovaginal reconstruction using an SIS graft is safe and efficient to the management of congenital cervicovaginal atresia whatever by the conventional laparoscopy, robotic surgery or LESS, with good surgical outcomes and high of quality of life.

Efficacy and safety of pelvic organ prolapse surgery with porcine small intestinal submucosa graft implantation

ObjectiveThe ideal implant material for the surgical repair of pelvic organ prolapse in women is yet to be found. This retrospective study aims to evaluate a porcine small intestinal submucosa (SIS) graft (Surgisis™). Study designWe reviewed the medical records of women that were operated upon for pelvic organ prolapse using implantation of SIS graft and we examined the short-term complications and recurrence rates. ResultsA total of 155 surgical procedures were reviewed. SIS graft was placed in the anterior, posterior and middle compartments in 93 (60%), 71 (45.8%) and 13 (8.4%) cases, respectively. At three-month follow-up, 22.6% of anterior graft repairs displayed anatomical recurrence (POP-Q stage ≥ 2), compared to 4.8% of posterior and none of the middle compartment graft repairs. During the three postoperative months, 56% of the women were recorded with complications, mostly urinary retention (19%) and pain (12%). The incidence of grade III complications was 5.3%. Persistent complications at three months were observed in 28% of all cases. Logistic regression analysis showed that previous prolapse surgery at the same compartment was a significant predictor for recurrence of prolapse after SIS graft application, whereas lower age, smoking and longer duration of surgery were significant predictors for the development of complications. Younger women had higher risk of developing pain postoperatively. ConclusionPain and urinary tract symptoms hold a central position in the complications profile of SIS graft-augmented prolapse surgery. The relatively high recurrence rates do not suggest a clear benefit from SIS graft use.

Histological Study On Using Ileal Submucosa In Repairing Urinary Bladder Defect In Adult Albino Rat

Abstract Background Repairing urinary bladder (UB) defect by enterocystoplasty remains the gold standard surgical bladder reconstruction procedure to increase the capacity and compliance of dysfunctional bladders. However, many complications were recorded. Aim of the work This work aimed to compare the consequences of reconstruction of urinary bladder defect using untreated small intestinal submucosal (SIS) matrix versus seeded and unseeded decellularized SIS matrix. Material and Methods Fifty female albino rats were used in this study. The animals were divided into three groups: Group I (Control) included ten adult rats from which ileal tissue was obtained. Group II included ten adult rats in which their UB defect was repaired by untreated cellular SIS. Group III included twenty adult rats that were subdivided into two subgroups, 10 rats each; Subgroup IIIA where rats had their UB defect repaired by acellular SIS and subgroup IIIb where rats had their UB defect repaired by acellular SIS seeded with adipose mesenchymal stem cells (AMSCs).Ten young rats were used for preparation of AMSCs. Morphometric and statistical analysis were also performed. Results In rats where UB defect was repaired by untreated cellular SIS, the graft area showed loss of epithelial polarity, presence of intraepithelial cysts and occasional extension of urothelium to the outer surface forming fistula. There were areas of metaplasia with the appearance PAS positive cells. In the lamina propria, there was areas of lymphocytic infiltration together with significant increase in the collagen fiber deposition (p &amp;lt; 0.05). There was a significant decrease thickness of muscle layer as compared to control (p &amp;lt; 0.05). In rats where UB defect was repaired by acellular SIS, urothelium in the graft area showed occasional squamous metaplasia and often the urothelium extended to the deeper layers forming Brunn's nest. There was minimal muscle regeneration in the graft area. However, in rats where UB defect was repaired by acellular SIS seeded with AMSCs, the urothelium in the graft area was nearly similar to control group with uniform urothelium thickness, minimal collagen fibers deposition and thick muscle layer that showed no significant difference from the control (p &amp;gt; 0.05). Conclusion Acellular SIS seeded with AMSCs showed better results compared to non-seeded and cellular SIS in reconstructing urinary bladder defects.

PERICARDIAL INJECTION OF MICRONIZED MATRIX BIOMATERIAL FOR POST-INFARCT CARDIAC REPAIR

BACKGROUND Injection of micronized biomaterials into the pericardial space is a potential less invasive approach to enhance post-infarct cardiac repair (Image). We have shown that porcine small intestinal submucosal extracellular matrix (SIS-ECM) biomaterials contain fibroblast growth factor-2 (FGF-2); and epicardial application of a SIS-ECM patch over ischemic myocardium promotes reparative post-infarct cardiac remodeling by upregulating vasculogenesis and downregulating fibrosis. Micronizing SIS-ECM into an injectable platform will allow pericardial delivery without the need for invasive surgery. Herein, we demonstrate improved post-infarct cardiac recovery after delivering micronized SIS-ECM powder into the pericardial space in in mice and we explore cellular mechanisms using three-dimensional fibroblast cultures. METHODS AND RESULTS In an intact pericardium mouse infarct model, coronary ligation (infarct) was performed through an unopened/undisrupted pericardium followed by pericardial injection of micronized SIS-ECM suspended in saline (treatment; n=12) or saline (control; n=10). Pressure-volume loops assessed cardiac function after 28 days. Mice receiving pericardial injection of micronized SIS-ECM had higher ejection fraction, lower ventricular stiffness (end diastolic pressure volume relationship; EDPVR), higher stroke work and higher cardiac output compared to saline control. Improved diastolic function represented by ventricular stiffness is suggestive of attenuated fibrosis and improved ventricular compliance. Three-dimensional cell cultures of mouse 3T3 cell line fibroblasts in collagen matrices assessed cellular response when exposed to either biomaterial-conditioned media with eluted growth factors (treatment) or untreated media (control). Collagen gels contract when fibroblasts take on a profibrotic phenotype, reducing in size on a macroscopic level. Additionally, paracrine activity of fibroblasts is measured using multiplex analysis with focus on angiogenic VEGF protein and fibrotic MMP-2 protease. Collagen gel contraction and MMP-2 release were attenuated by biomaterial factors, suggesting reduced fibrotic activity. Micronized SIS-ECM increased VEGF production from fibroblasts. Adding an FGF-2 inhibitor to biomaterial-conditioned media negated the biomaterial's effects, thereby increasing gel contraction and MMP-2 release, highlighting the key role of FGF-2 in attenuating fibroblast activity. Table 1 contains outcomes from all studies. CONCLUSION Pericardial injection of micronized SIS-ECM promotes reparative fibroblast activity, increases production of angiogenic VEGF protein, and preserves post-infarct cardiac compliance and function. Pericardial injection is a less invasive modality that may facilitate early intervention to attenuate maladaptive post-infarct structural remodeling. Future study into mechanism and large animal infarct models will be required to identify key cellular pathways and develop percutaneous strategies for clinical translation. Injection of micronized biomaterials into the pericardial space is a potential less invasive approach to enhance post-infarct cardiac repair (Image). We have shown that porcine small intestinal submucosal extracellular matrix (SIS-ECM) biomaterials contain fibroblast growth factor-2 (FGF-2); and epicardial application of a SIS-ECM patch over ischemic myocardium promotes reparative post-infarct cardiac remodeling by upregulating vasculogenesis and downregulating fibrosis. Micronizing SIS-ECM into an injectable platform will allow pericardial delivery without the need for invasive surgery. Herein, we demonstrate improved post-infarct cardiac recovery after delivering micronized SIS-ECM powder into the pericardial space in in mice and we explore cellular mechanisms using three-dimensional fibroblast cultures. In an intact pericardium mouse infarct model, coronary ligation (infarct) was performed through an unopened/undisrupted pericardium followed by pericardial injection of micronized SIS-ECM suspended in saline (treatment; n=12) or saline (control; n=10). Pressure-volume loops assessed cardiac function after 28 days. Mice receiving pericardial injection of micronized SIS-ECM had higher ejection fraction, lower ventricular stiffness (end diastolic pressure volume relationship; EDPVR), higher stroke work and higher cardiac output compared to saline control. Improved diastolic function represented by ventricular stiffness is suggestive of attenuated fibrosis and improved ventricular compliance. Three-dimensional cell cultures of mouse 3T3 cell line fibroblasts in collagen matrices assessed cellular response when exposed to either biomaterial-conditioned media with eluted growth factors (treatment) or untreated media (control). Collagen gels contract when fibroblasts take on a profibrotic phenotype, reducing in size on a macroscopic level. Additionally, paracrine activity of fibroblasts is measured using multiplex analysis with focus on angiogenic VEGF protein and fibrotic MMP-2 protease. Collagen gel contraction and MMP-2 release were attenuated by biomaterial factors, suggesting reduced fibrotic activity. Micronized SIS-ECM increased VEGF production from fibroblasts. Adding an FGF-2 inhibitor to biomaterial-conditioned media negated the biomaterial's effects, thereby increasing gel contraction and MMP-2 release, highlighting the key role of FGF-2 in attenuating fibroblast activity. Table 1 contains outcomes from all studies. Pericardial injection of micronized SIS-ECM promotes reparative fibroblast activity, increases production of angiogenic VEGF protein, and preserves post-infarct cardiac compliance and function. Pericardial injection is a less invasive modality that may facilitate early intervention to attenuate maladaptive post-infarct structural remodeling. Future study into mechanism and large animal infarct models will be required to identify key cellular pathways and develop percutaneous strategies for clinical translation.

Immunosuppressed Miniswine as a Model for Testing Cell Therapy Success: Experience With Implants of Human Salivary Stem/Progenitor Cell Constructs.

An urgent need exists to develop large animal models for preclinical testing of new cell therapies designed to replace lost or damaged tissues. Patients receiving irradiation for treatment of head and neck cancers frequently develop xerostomia/dry mouth, a condition that could one day be treated by cell therapy to repopulate functional saliva-producing cells. Using immunosuppression protocols developed for patients receiving whole face transplants, we successfully used immunosuppressed miniswine as a suitable host animal to evaluate the long-term stability, biocompatibility, and fate of matrix-modified hyaluronate (HA) hydrogel/bioscaffold materials containing encapsulated salivary human stem/progenitor cells (hS/PCs). An initial biocompatibility test was conducted in parotids of untreated miniswine. Subsequent experiments using hS/PC-laden hydrogels were performed in animals, beginning an immunosuppression regimen on the day of surgery. Implant sites included the kidney capsule for viability testing and the parotid gland for biointegration time periods up to eight weeks. No transplant rejection was seen in any animal assessed by analysis of the tissues near the site of the implants. First-generation implants containing only cells in hydrogel proved difficult to handle in the surgical suite and were modified to adhere to a porcine small intestinal submucosa (SIS) membrane for improved handling and could be delivered through the da Vinci surgical system. Several different surgical techniques were assessed using the second-generation 3D-salivary tissue (3D-ST) for ease and stability both on the kidney capsule and in the capsule-less parotid gland. For the kidney, sliding the implant under the capsule membrane and quick stitching proved superior to other methods. For the parotid gland, creation of a tissue “pocket” for placement and immediate multilayer tissue closure were well tolerated with minimal tissue damage. Surgical clips were placed as fiduciary markers for tissue harvest. Some implant experiments were conducted with miniswine 90 days post-irradiation when salivation decreased significantly. Sufficient parotid tissue remained to allow implant placement, and animals tolerated immunosuppression. In all experiments, viability of implanted hS/PCs was high with clear signs of both vascular and nervous system integration in the parotid implants. We thus conclude that the immunosuppressed miniswine is a high-value emerging model for testing human implants prior to first-in-human trials.

Small Intestinal Submucosa Membrane Modified by Fusion Peptide-Mediated Extracellular Vesicles to Promote Tissue Regeneration.

Tissue injury, which often occurs in daily life, remains challenging in clinical medicine. Developing a novel biomaterial with the capability to provide an ideal microenvironment and homeostasis around the wound is highly desirable for effective tissue regenerative medicine. The small intestinal submucosa (SIS) membrane possesses a precise spatial structure with excellent biocompatibility. Extracellular vesicles (EVs) derived from umbilical cord mesenchymal stem cells can achieve rapid cell proliferation and migration with little immune response by creating a satisfactory microenvironment. In this study, fusion peptide-mediated EVs are able to modify the surface of the SIS membrane via specific combination. In vitro studies prove that modified SIS membranes can promote cell migration and spreading. This phenomenon may be because of the activation of TEADs, which regulate cell behavior. By constructing a rat abdominal wall defect model, it is further demonstrated that the modified SIS membrane is more conducive to tissue regeneration. Collectively, these results suggest that SIS membranes modified by fusion peptide-mediated EVs achieve excellent biofunction and provide promising prospects for tissue regeneration.

Effects of hypoxia on Achilles tendon repair using adipose tissue-derived mesenchymal stem cells seeded small intestinal submucosa

BackgroundThe study was performed to evaluate the feasibility of utilizing small intestinal submucosa (SIS) scaffolds seeded with adipose-derived mesenchymal stem cells (ADMSCs) for engineered tendon repairing rat Achilles tendon defects and to compare the effects of preconditioning treatments (hypoxic vs. normoxic) on the tendon healing.MethodsFifty SD rats were randomized into five groups. Group A received sham operation (blank control). In other groups, the Achilles tendon was resected and filled with the original tendon (Group B, autograft), cell-free SIS (Group C), or SIS seeded with ADMSCs preconditioned under normoxic conditions (Group D) or hypoxic conditions (Group E). Samples were collected 4 weeks after operation and analyzed by histology, immunohistochemistry, and tensile testing.ResultsHistologically, compared with Groups C and D, Group E showed a significant improvement in extracellular matrix production and a higher compactness of collagen fibers. Group E also exhibited a significantly higher peak tensile load than Groups D and C. Additionally, Group D had a significantly higher peak load than Group C. Immunohistochemically, Group E exhibited a significantly higher percentage of MKX + cells than Group D. The proportion of ADMSCs simultaneously positive for both MKX and CM-Dil observed from Group E was also greater than that in Group D.ConclusionsIn this animal model, the engineered tendon grafts created by seeding ADMSCs on SIS were superior to cell-free SIS. The hypoxic precondition further improved the expression of tendon-related genes in the seeded cells and increased the rupture load after grafting in the Achilles tendon defects.

Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes.

The neonatal heart represents an attractive source of regenerative cells. Here, we report the results of a randomized, controlled, investigator-blinded preclinical study, which assessed the safety and effectiveness of a matrix graft cellularized with cardiac pericytes (CPs) in a piglet model of pulmonary artery (PA) reconstruction. Within each of five trios formed by 4-week-old female littermate piglets, one element (the donor) was sacrificed to provide a source of CPs, while the other two elements (the graft recipients) were allowed to reach the age of 10 weeks. During this time interval, culture-expanded donor CPs were seeded onto swine small intestinal submucosa (SIS) grafts, which were then shaped into conduits and conditioned in a flow bioreactor. Control unseeded SIS conduits were subjected to the same procedure. Then, recipient piglets were randomized to surgical reconstruction of the left PA (LPA) with unseeded or CP-seeded SIS conduits. Doppler echocardiography and cardiac magnetic resonance imaging (CMRI) were performed at baseline and 4-months post-implantation. Vascular explants were examined using histology and immunohistochemistry. All animals completed the scheduled follow-up. No group difference was observed in baseline imaging data. The final Doppler assessment showed that the LPA’s blood flow velocity was similar in the treatment groups. CMRI revealed a mismatch in the average growth of the grafted LPA and contralateral branch in both treatment groups. Histology of explanted arteries demonstrated that the CP-seeded grafts had a thicker luminal cell layer, more intraparietal arterioles, and a higher expression of endothelial nitric oxide synthase (eNOS) compared with unseeded grafts. Moreover, the LPA stump adjacent to the seeded graft contained more elastin and less collagen than the unseeded control. Syngeneic CP engineering did not accomplish the primary goal of supporting the graft’s growth but was able to improve secondary outcomes, such as the luminal cellularization and intraparietal vascularization of the graft, and elastic remodeling of the recipient artery. The beneficial properties of neonatal CPs may be considered in future bioengineering applications aiming to reproduce the cellular composition of native arteries.

The Different Effect of Decellularized Myocardial Matrix Hydrogel and Decellularized Small Intestinal Submucosa Matrix Hydrogel on Cardiomyocytes and Ischemic Heart

Injectable decellularized matrix hydrogels derived from either myocardium or small intestinal submucosa (pDMYO-gel, pDSIS-gel) have been successfully used for myocardial injury repair. However, the relationship between tissue-specific biological functions and protein composition in these two materials is not clear yet. In this study, the protein composition, mechanical properties, and morphology of these two hydrogels and their effects on the behavior of neonatal rat cardiomyocytes (NRCMs) and human umbilical vein endothelial cells (HUVECs), are investigated. The results show that pDMYO-gel is more conducive to growth, adhesion, spreading, and maintenance of normal NRCM beating, due to its higher proportion of extracellular matrix (ECM) glycoproteins (49.55%) and some unique functional proteins such as annexin-6 (ANXA6), agrin (AGRN), cathepsin D (CTSD) and galectin-1 (LGALS1), whereas pDSIS-gel is more conducive to the proliferation of HUVECs. Animal study shows that pDMYO-gel has a better effect on improving cardiac function, inhibiting myocardial fibrosis and maintaining ventricular wall thickness in acute myocardial infarction models in vivo. Therefore, it is proposed that injectable pDMYO-gel hydrogel may be more suitable for functional recovery of myocardial injuries.

Repair of long bone defects of large size using a tissue-engineered periosteum in a rabbit model

Tissue engineering is a promising approach for bone regeneration. In this study, we aimed to investigate whether tissue engineered periosteum (TEP), which was fabricated by combining osteogenically-induced mesenchymal stem cells (MSCs) with porcine small intestinal submucosa (SIS), could restore long bone defects of large size in rabbits. Twenty-four adult New Zealand white rabbits (NZWRs) were used in the experiments. Long bone defects of large size (30 mm-50 mm; average, 40 mm) were established on both sides of NZWRs’ radii. The defects were treated with TEP (Group A), allogeneic deproteinized bone (DPB, Group B), TEP combined with DPB (Group C), and pure SIS (Group D). The healing outcome was evaluated by radiography and histological examination at 4, 8, and 12 weeks post-treatment. The radiographical findings showed that bone defects of large size were all repaired in Groups A, B and C within 12 weeks, whereas Group D (pure SIS group) failed to result in defect healing at 4, 8, and 12 weeks. Although there was some new bone regeneration connecting the allografts and bone ends, as observed under radiographical and histological observations, bone defects of large sizes were restored primarily by structurally allografted DPB within 12 weeks. The TEP groups (Groups A and C) showed partial or total bone regeneration upon histological inspection. Based on 12-week histological examinations, significantly more bone was formed in Group A than Group C (P < 0.05), and both groups formed significantly more bone than in Groups B and D. The results indicated that long bone defects of a large size could be restored by TEP or TEP combined with the DPB scaffold, and such materials provide an alternative approach to resolving pathological bone defects in clinical settings.

Reversal of unstable atrial fibrillation after surgical correction of hiatus hernia: A case report.

IntroductionThe presence of Atrial Fibrillation (AF) with herniation of abdominal content through the esophageal hiatus can be explained by the compression of the cardiac tissue by the viscera and, consequently, of its electrical transmission network, compromising the correct propagation of stimuli.Due to the causal relationship, hernia correction is almost always able to reverse the arrhythmic picture.Presentation of the caseA 75-year-old male with atrial fibrillation with a large hiatal hernia causing clinical decompensation was successfully treated after a laparocopic correction- primary closure of the defect was made with barbed surgical thread plus and placing a biological mesh (porcine small intestine submucosa, non-cross-linked), fixed with cyanoacrylate; after the procedure, he was discharged asymptomatic and with sinus heart rhythm.DiscussionIt is noticed that for cases in which the patient presents with a type IV hiatal hernia associated with atrial fibrillation, the laparoscopic correction of hernia using a mesh for the correction of the defect has good results in the literature.In the present case, it is noted that despite the severity of the condition denoted by hemodynamic instability and the need for electrical cardioversion, the surgical correction of the hiatal hernia was able to reverse the arrhythmic picture definitively.Conclusionthe concomitance of AF and hiatal hernia can explain the difficulty to control the arrhythmic picture and is necessary to consider, as soon as possible, the surgical correction of the defect as part of the treatment.

A Comparative Study of Porcine Small Intestine Submucosa and Cross-Linked Bovine Type I Collagen as a Nerve Conduit

PurposeWe compared 2 commercially available nerve conduits—the Axoguard Nerve Connector, made of porcine small intestine submucosa (SIS), and the NeuraGen Nerve Guide, made of cross-linked bovine type I collagen (Col)—using a rodent model at 4 weeks, specifically focusing on subchronic host responses to the implants.MethodsA unilateral 5-mm sciatic nerve defect was created in 18 male Lewis rats and was repaired with SIS or Col conduits. After 4 weeks, histological evaluations of morphology, collagen content, macrophage polarization, vascularization, axonal regeneration, and myelination were conducted. To achieve a blinded examination, an independent qualified pathologist evaluated the images that were stained with hematoxylin-eosin, α-smooth muscle actin, and Masson trichrome stains.ResultsThe results showed a dominant macrophage type 2 (M2) response in the SIS group and a dominant macrophage type 1 (M1) response in the Col group. The SIS group showed deeper implant vascularization and fibroblast ingrowth than the Col group. Collagen deposition was higher within the lumen of the Col group than the SIS group. All Col conduits were surrounded by a colocalized staining of Masson trichrome and α-smooth muscle actin, forming a capsule-like structure.ConclusionDistinctive histological features were identified for each conduit at the cellular level. The SIS conduits had a significantly higher number of host macrophages expressing M2 surface marker CD163, and the Col conduits showed a predominance of host macrophages expressing the M1 surface marker CD80. Data suggest that promoting the M2 response for tissue engineering and regenerative medicine is associated with a remodeling response. In addition, an independent analysis revealed an encapsulation-like appearance around all Col conduits, which is similar to what is seen in breast implant capsules.Clinical relevanceThe biomaterial choice for conduit material can play an important role in the host tissue response, with the potential to impact adverse events and patient outcomes.

De Novo Valve Tissue Morphology Following Bioscaffold Mitral Valve Replacement in a Juvenile Non-Human Primate Model.

The utility of implanting a bioscaffold mitral valve consisting of porcine small intestinal submucosa (PSIS) in a juvenile baboon model (12 to 14 months old at the time of implant; n = 3) to assess their in vivo tissue remodeling responses was investigated. Our findings demonstrated that the PSIS mitral valve exhibited the robust presence of de novo extracellular matrix (ECM) at all explantation time points (at 3-, 11-, and 20-months). Apart from a significantly lower level of proteoglycans in the implanted valve’s annulus region (p < 0.05) at 3 months compared to the 11- and 20-month explants, there were no other significant differences (p > 0.05) found between any of the other principal valve ECM components (collagen and elastin) at the leaflet, annulus, or chordae tendinea locations, across these time points. In particular, neochordae tissue had formed, which seamlessly integrated with the native papillary muscles. However, additional processing will be required to trigger accelerated, uniform and complete valve ECM formation in the recipient. Regardless of the specific processing done to the bioscaffold valve, in this proof-of-concept study, we estimate that a 3-month window following bioscaffold valve replacement is the timeline in which complete regeneration of the valve and integration with the host needs to occur.

Curcumin in decellularized goat small intestine submucosa for wound healing and skin tissue engineering.

Biomaterials derived from extracellular matrices (ECMs) were extensively used for skin tissue engineering and wound healing. ECM is a complex network of biomolecules (e.g., proteins), which provide organizational support to cells for growth. Thus, ECM could be an ideal biomaterial for fabricating the scaffold. However, oxidative stress and biofilm formation at the wound site remains a major challenge that could be neutralized using herbal ingredients (e.g., curcumin). In this study, ECM was extracted from the biowaste of the goat abattoir by using decellularization. The goat small intestine submucosa (G-SIS) is decellularized to obtain the decellularized G-SIS (DG-SIS) and curcumin (in different concentrations) was incorporated in the DG-SIS to fabricate curcumin-embedded DG-SIS scaffolds. Changes brought by increasing the concentrations of the curcumin in DG-SIS were observed in various properties, including free radical scavenging and antibacterial properties. Results depicted that the scaffolds are porous, biodegradable, biocompatible, antibacterial, and hydrophilic and showed sustained release of curcumin. Besides, it showed free radicals scavenging property. The porosity and hydrophilicity of the scaffolds were decreased with an increase in the curcumin content. However, biodegradability, free radical scavenging, biocompatibility, and antibacterial properties of the scaffolds increased with an increase in the curcumin content. The DG-SIS scaffold containing 1 wt % of curcumin may be a potential biomaterial for wound-healing and skin tissue engineering.