Stem cell augmented mesh materials: an in vitro and in vivo study

INTRODUCTION AND HYPOTHESIS: To test in vitro and in vivo the capability of mesh materials to act as scaffolds for rat-derived mesenchymal stem cells (rMSCs) and to compare inflammatory response and collagen characteristics of implant materials, either seeded or not with rMSCs. METHODS: rMSCs isolated from rat bone marrow were seeded and cultured in vitro on four different implant materials. Implants showing the best rMSC proliferation rate were selected for the in vivo experiment. Forty-eight adult female Sprague-Dawley rats were randomly divided into two treatment groups. The implant of interest-either seeded or not with rMSCs-was laid and fixed over the muscular abdominal wall. Main outcome measures were: in vitro, proliferation of rMSCs on selected materials; in vivo, the occurrence of topical complications, the evaluation of systemic and local inflammatory response and examination of the biomechanical properties of explants. RESULTS: Surgisis and Pelvitex displayed the best cell growth in vitro. At 90 days in the rat model, rMSCs were related to a lower count of neutrophil cells for Pelvitex and a greater organisation and collagen amount for Surgisis. At 7 days Surgisis samples seeded with rMSCs displayed higher breaking force and stiffness. CONCLUSIONS: The presence of rMSCs reduced the systemic inflammatory response on synthetic implants and improved collagen characteristics at the interface between biological grafts and native tissues. rMSCs enhanced the stripping force on biological explants

Diaphragm Repair with a Novel Cross-Linked Collagen Biomaterial in a Growing Rabbit Model.

Neonates with congenital diaphragmatic hernia and large defects often require patch closure. Acellular collagen matrices (ACM) have been suggested as an alternative to synthetic durable patches as they are remodeled by the host or could also be used for tissue engineering purposes.2.0x1.0 cm diaphragmatic defects were created in 6-weeks old New-Zealand white rabbits. We compared reconstruction with a purpose-designed cross-linked ACM (Matricel) to 4-layer non-cross-linked small intestinal submucosa (SIS) and a 1-layer synthetic Dual Mesh (Gore-Tex). Unoperated animals or animals undergoing primary closure (4/0 polyglecaprone) served as age-matched controls. 60 (n = 25) resp. 90 (n = 17) days later, animals underwent chest x-ray and obduction for gross examination of explants, scoring of adhesion and inflammatory response. Also, uniaxial tensiometry was done, comparing explants to contralateral native diaphragmatic tissue.Overall weight nearly doubled from 1,554±242 g at surgery to 2,837±265 g at obduction (+84%). X-rays did show rare elevation of the left diaphragm (SIS = 1, Gore-Tex = 1, unoperated control = 1), but no herniation of abdominal organs. 56% of SIS and 10% of Matricel patches degraded with visceral bulging in four (SIS = 3, Matricel = 1). Adhesion scores were limited: 0.5 (Matricel) to 1 (SIS, Gore-Tex) to the left lung (p = 0.008) and 2.5 (Gore-Tex), 3 (SIS) and 4 (Matricel) to the liver (p<0.0001). Tensiometry revealed a reduced bursting strength but normal compliance for SIS. Compliance was reduced in Matricel and Gore-Tex (p<0.01). Inflammatory response was characterized by a more polymorphonuclear cell (SIS) resp. macrophage (Matricel) type of infiltrate (p<0.05). Fibrosis was similar for all groups, except there was less mature collagen deposited to Gore-Tex implants (p<0.05).Matricel induced a macrophage-dominated inflammatory response, more adhesions, had appropriate strength but a lesser compliance compared to native tissue. The herein investigated ACM is not a viable option for CDH repair

Coexistent Detrusor Overactivity-Underactivity in Patients with Pelvic Floor Disorders

Introduction and Hypothesis: Pelvic floor disorders represent a series of conditions that share, in part, the same etiological mechanisms, so they tend to be concomitant. Recently, awareness of a new lower urinary tract clinical syndrome has risen, namely the coexisting overactive–underactive bladder (COUB). The etiopathogenetic process, prevalence, and related instrumental findings of COUB are not well-established. We aimed to evaluate the prevalence, clinical features, and urodynamic findings of patients with COUB in a large cohort of patients with pelvic floor disorders. Methods: A cohort of 2092 women was retrospectively analyzed. A clinical interview, urogenital examination, and urodynamic assessment were performed by a trained urogynecologist. Based on baseline symptoms, patients were divided into COUB and non-COUB groups, and the degree of concordance between COUB and urodynamic findings, and other parameters related to the clinical aspects of these patients were measured and analyzed. Results: 18.8% of patients were classified as COUB. The association between COUB and patients with coexisting detrusor overactivity–underactivity (DOU) was statistically significant and there were substantial similarities in terms of population characteristics, symptoms, and urodynamic findings. Conclusions: Our study showed a high prevalence of COUB, and a link between this clinical syndrome and DOU was demonstrated. They showed substantial similarities in terms of clinical and urodynamics correlates. Based on these findings, we do think that urodynamic tests can be useful to improve knowledge on COUB and may be of help in the management of this condition

Surgical procedure.

<p>A left-dorsolateral thoracotomy was performed to expose the diaphragm. After placement of a traction suture (A, <i>arrow</i>) a 2.0 x 1.0 cm defect was cut in the tendomuscular part of the diaphragm and repaired by either placing a running suture (B) or inserting a cone-shaped patch (C, D) made from different materials.</p

Histology.

<p>Representative micrographs of all groups (columns) obtained at x400 magnification with identical settings for each stain from the mesh-tissue interface. Meshes are invisible form degradation or processing, respectively. Inflammation is represented by the number of macrophages (first row, black arrows), foreign body giant cells (second row, black arrows) and polymorphonuclear cells (second row, white arrows), fibrosis depicted by the amount of neovascularization (second row, v vessel) as well as the amount and composition of collagen (third row, * muscle, ⏏ mature collagen, ⌃ immature collagen, ★ patch). H&E: Hematoxylin-eosin.</p

Macroscopic findings.

<p>A. Primary repair (d60), polyglecaprone suture absorbed (<i>arrow</i>). B. Gore-Tex (d 60), encapsulated with perihepatic adhesions. Matricel patches were preserved in all (d60; C) but one animal (d90; D, <i>arrow =</i> patch remnant) with high-grade perihepatic adhesions (D). SIS patches were degraded in five animals with bulging of viscera in three (d60, E). Seroma was observed twice (d 60, F, <i>asterisk</i>).</p