Effects Of Small Intestinal Submucosa Research Articles

No midterm advantages in the middle term using small intestinal submucosa and human amniotic membrane in Achilles tendon transverse tenotomy.

BackgroundThe study was aimed to compare the effects of small intestinal submucosa (SIS) and human amniotic membrane (HAM) on Achilles tendon healing.MethodsA total of 48 New Zealand white rabbits were divided into two groups. A full-thickness transverse tenotomy was made at the right leg of the rabbits. Then, the laceration site was wrapped with HAM (P/A group) or SIS (P/S group). The ultimate stress (US) and Young’s modulus (E) of the tendons were detected for biomechanical analysis. Histological evaluation was performed using hematoxylin and eosin, immunohistochemical, and immunofluorescent stain. Expression of collagen I was detected by western blot analysis, and levels of inflammatory cytokines IL-1β, IL-6, and TNF-α were measured. Finally, adhesion formation was evaluated.ResultsThere were no significant differences in filamentous adhesion, cross-sectional areas of the laceration sites, levels of inflammatory response, and collagen type I expression between the P/A and P/S groups (p > 0.05). Compared with the P/A group, the US and E values were significantly higher in the P/S group at day 7 (p < 0.05) and at day 14 (p < 0.05). In addition, vascularity was significantly higher in the P/S group than that in the P/A group at day 3 (p < 0.05), day 7 (p < 0.01), and day 9 (p < 0.05).ConclusionsSIS showed superior biomechanical properties and neovascularization over HAM in treatment of Achilles tendon injury in the early stage of healing.

Effect of small intestinal submucosa sponges on the attachment and proliferation behavior of Schwann cells

The aim of the study was to investigate the effects of small intestinal submucosa (SIS) sponges, a natural biodegradable polymer scaffold, on the adhesion behavior and the proliferation of Schwann cells (SCs). SIS sponges were prepared by varying the contents of SIS powders (1%, 2%, and 3% SIS concentration) and SCs were seeded on the sponges and incubated to investigate the adhesion and proliferation of SCs. A series of analytical process was conducted to observe the water absorption rate of sponges and confirmed the proliferation and morphology of SCs by scanning electron microscopy (SEM), 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, reverse transcription polymerase chain reaction (RT-PCR), and histological evaluation. The best adhesion behavior and the proliferation of SCs were observed on the sponge with 2% powder content. Also, analysis of messenger ribonucleic acid (mRNA) expression using the neuron-specific enolase (NSE) and neurofilament protein (NF) nerve markers showed that SC gene expression was excellent in the 2% SIS sponge. In vivo hematoxylin and eosin (H&E) staining and immunofluorescence results showed that cells and tissue formed well in the pores of sponges with 2% and 3% SIS powder contents, compared with formation in the 1% SIS sponge. The SIS sponges provided an unsuitable habitat for the adhesion and proliferation of cells in that the pore size was small. In this study, the adhesion behavior and the proliferation could be changed depending on the pore size and SIS powder content in the sponges. Thus, an appropriate powder content of SIS should be used to prepare SIS sponge scaffolds.

Effects of Small Intestinal Submucosa (SIS) on the Murine Innate Immune Microenvironment Induced by Heat-Killed Staphylococcus aureus

The use of biological scaffold materials for wound healing and tissue remodeling has profoundly impacted regenerative medicine and tissue engineering. The porcine-derived small intestinal submucosa (SIS) is a licensed bioscaffold material regularly used in wound and tissue repair, often in contaminated surgical fields. Complications and failures due to infection of this biomaterial have therefore been a major concern and challenge. SIS can be colonized and infected by wound-associated bacteria, particularly Staphylococcus aureus. In order to address this concern and develop novel intervention strategies, the immune microenvironment orchestrated by the combined action of S. aureus and SIS should be critically evaluated. Since the outcome of tissue remodeling is largely controlled by the local immune microenvironment, we assessed the innate immune profile in terms of cytokine/chemokine microenvironment and inflammasome-responsive genes. BALB/c mice were injected intra-peritoneally with heat-killed S. aureus in the presence or absence of SIS. Analyses of cytokines, chemokines and microarray profiling of inflammasome-related genes were done using peritoneal lavages collected 24 hours after injection. Results showed that unlike SIS, the S. aureus-SIS interactome was characterized by a Th1-biased immune profile with increased expressions of IFN-γ, IL-12 and decreased expressions of IL-4, IL-13, IL-33 and IL-6. Such modulation of the Th1/Th2 axis can greatly facilitate graft rejections. The S. aureus-SIS exposure also augmented the expressions of pro-inflammatory cytokines like IL-1β, Tnf-α, CD30L, Eotaxin and Fractalkine. This heightened inflammatory response caused by S. aureus contamination could enormously affect the biocompatibility of SIS. However, the mRNA expressions of many inflammasome-related genes like Nlrp3, Aim2, Card6 and Pycard were down-regulated by heat-killed S. aureus with or without SIS. In summary, our study explored the innate immune microenvironment induced by the combined exposure of SIS and S. aureus. These results have practical implications in developing strategies to contain infection and promote successful tissue repair.

Effect of submucosa of small intestine on intestinal anastomosis in goats

The aim of this study was to investigate the effect of small intestinal submucosa (SIS) on the healing of intestinal anastomosis in goats. Twelve local breed bucks were used. Animals were divided into two equal groups, in the first group the anastomotic site after resection of 4 cm from the jejunum was sutured by horizontal mattress pattern, considered as a control group. In the second group, after anastomose was covered by small intestinal submucosa,prepared previously and fixed with the anastomotic site by multiple stitches of a simple interrupted suture. Experimental animals were observed clinically, after 15 and 30 days postoperation, the sample of anastomosis site were examined grossly and histopathologically. Grossly in control group moderate to severe adhesion of anastomotic site with the surrounding tissue was found as compared with the moderate adhesion in the treated group. The bursting pressure, in control group, was (150±2.9) and (178.3±4.5) mmHg, while in the treated group was (185±2.9) and (208.3±4.5) mmHg at a period of 15 and 30 days post operation respectively. The degree of stenosis in control group was (59±1.5) and (49±2.2), while in the treated group was (76±5.6) and (36.3±0.6) at a period of 15 and 30 days post operation respectively. The histopathological findings revealed that the healing process was more prominent in the treated group than in the control group. In conclusion of this study investigated that submucosa of small intestine enhances healing of intestinal anastomosis.

Effects of porcine small intestinal submucosa on elution characteristics of gentamicin-impregnated plaster of Paris

To evaluate effects of small intestinal submucosa (SIS) on elution properties of plaster of Paris (POP). 27 POP cylinders, 27 POP spheres, and 9 polymethylmethacrylate (PMMA) spheres. Pellets were loaded with gentamicin (50 mg/g) and divided into 7 groups of 9 beads each: PMMA spheres; POP cylinders coated with 0, 4, or 8 layers of SIS; and POP spheres coated with 0, 4, or 8 layers of SIS. Gentamicin concentration was measured 6, 12, 18, 24, 32, 40, and 48 hours and 3, 4, 5, 7, 14, 21, 28, 35, and 42 days after wrapping. Porosity was evaluated via scanning electron microscopy. Curvature factor of elution curves, total amount of drug released (TDR), time required to reach 50% of total release (TDR(t50)), and number of days with concentrations > or = 1 microg/mL were compared among groups. SIS decreased the curvature factor and increased the TDR(t50) and TDR of POP spheres and cylinders. Curvature factor of the PMMA-release curve remained lower than that for any POP group, but all POP groups wrapped in SIS released more gentamicin than PMMA spheres. Gentamicin concentrations remained > or = 1 microg/mL in SIS-wrapped POP and PMMA groups throughout the study. Wrapping POP in SIS minimized the increase in porosity of pellets. Wrapping POP with SIS slows the release and increases the amount of gentamicin leaching from spheres and cylinders. All groups wrapped in SIS maintained antimicrobial concentrations greater than the minimum inhibitory concentration of most pathogens.

Evaluation of a novel biomaterial for intrasubstance muscle laceration repair

The authors compare the effects of small intestinal submucosa (SIS) treatment to suture repair with respect to histologic and functional outcomes for complete muscle lacerations in a rabbit model. The authors hypothesized that SIS treatment of full-thickness muscle belly lacerations would significantly improve muscle function, strength, and regeneration compared to the current standard-of-care treatment. Muscle belly lacerations were created in the extensor digitorum longus (EDL) of both hind limbs of each rabbit. After randomization, lacerations were left unrepaired (n = 48) or repaired using a 4-0 Prolene modified Kessler stitch (n = 48). A flap of SIS graft was sutured into half (n = 24 each) of the repaired and unrepaired muscles forming four study groups. Suture repair with SIS augmentation of complete muscle lacerations resulted in healed tissue that most closely resembled normal muscle in terms of morphology and function when compared to current standard-of-care treatments. Active force production in this group reached 79% of uninjured controls 12 weeks after surgery. SIS may have important clinical advantages over suture repair alone and warrants further clinical study.

A pilot study to evaluate the effectiveness of small intestinal submucosa used to repair spinal ligaments in the goat

A pilot study to evaluate the effectiveness of small intestinal submucosa used to repair spinal ligaments in the goat

The effectiveness of small intestinal submucosa for spinal ligament repair in the goat

Allen L. Carl, MD, Eric H. Ledet, MS, Darryl DiRisio, MD, Michael P. Tymeson, MS, Lucille B. Andersen, MD, Bashkar Kallarury, MD, Albany, NY, USA; Michael Slivka, Hassan Serhan, PhD, Raynham, MA, USABackground context: Destabilization of the lumbar spine results from sacrifice of the anterior longitudinal ligament and disc when removed for graft or cage placement. Similarly, transection of the interspinous ligament during surgical approaches to the posterior spine may result in additional instability. Such instability can cause abnormal motion or implant migration resulting in a high incidence of pseudarthrosis. Small intestinal submucosa (SIS) is a naturally occurring extracellular collagen-based matrix, which is derived from the small intestine of pigs. SIS contains cytokines and growth factors and has been shown to act as a resorbable scaffold in vivo that promotes soft tissue regeneration with little scar tissue formation. SIS can be manufactured in laminated sheets of various sizes and thicknesses for different indications. Successful applications of SIS have included dural substitution, rotator cuff repair, tendinosis, vessel repair, abdominal and bladder wall repair and others. However, SIS has not been investigated to determine its ability to facilitate regeneration of spinal ligaments.Purpose: The purpose of this pilot study was to evaluate the efficacy of SIS to restore stability in the spine and act as a scaffold for regeneration of the anterior longitudinal ligament (ALL) and interspinous ligaments (ISL) in a goat model.Methods: Four skeletally mature nubian-alpine crossbred goats were used in this study. Under general anesthesia, each T10 to L5 motion segment was exposed surgically. Both an anteriolateral and posterior approach were made at each level. Anteriorly, every other level received either anterior discectomy, sacrifice of ALL and placement of SIS (”SIS”); anterior discectomy, sacrifice of ALL and no SIS (”control”); or sham operation (”sham”). A solid interbody spacer was placed into the disc space at each SIS and control level to prohibit spontaneous anterior interbody fusion. A sheet of SIS was applied to the ventral surface of each SIS level such that it spanned the disc space making intimate contact with the remaining ALL superiorly and inferiorly. The SIS was secured to the cranial and caudal vertebral bodies with bone staples, suture anchors and suture. Posteriorly, every other level received either sacrifice of the ISL with placement of SIS (”SIS”); sacrifice of ISL and no SIS (”control”); or sham operation (”sham”). At SIS levels, a sheet of SIS was applied dorsal to the spinous processes and wrapped over the left and right lateral aspect. The SIS was secured to the spinous processes with suture anchors. Sutures were passed through the SIS and around the adjacent spinous processes to create a tension-band effect. Animals were radiographed immediately postoperatively to confirm implant placement and to serve as a baseline for interbody spacer positioning. After surgery, all animals were allowed unrestricted motion for 12 weeks. At the end of the 12-week period, animals were radiographed and euthanized. The lumbar spine was harvested en bloc and processed for decalcified histologic evaluation. The dorsal and ventral aspects of each motion segment were analyzed for signs of inflammation and scar tissue formation, residual SIS and regenerated ALL or ISL.Results: All animals tolerated the surgical procedure well, and there were no intraoperative or anesthesia related complications. Immediate postoperative radiographs showed proper placement of all implants. Gross analysis at necropsy indicated iatrogenic scar formation, the degree of which was not different from controls to SIS levels. Histologic evaluation of areas where the ALL had been removed indicated formation of organized fibrillar collagenous tissue that spanned the disc space at some levels where the SIS was placed. The newly formed tissue was approximately 70% the thickness of the ALL at the sham level. Sparse focal areas of inflammation and no residual SIS at some levels accompanied the newly formed collagenous tissue. At control levels, there was limited formation of sparsely organized connective tissues. At sham levels, normal ligamentous structures were present. Similarly, histologic analysis of some levels where SIS was placed posteriorly showed formation of organized collagenous tissues where the ISL had been removed.Discussion: Placement of the SIS resulted in regeneration of the ligamentous-like tissues in the spine to a varying degree with limited signs of inflammation and scar formation. This result indicates the potential for SIS in repair of spinal ligaments for restabilization of the lumbar spine.