Biomechanical Features of Reinforced Esophageal Hiatus Repair in a Porcine Model.

Recurrence rates in the laparoscopic repair of the hiatal hernia range from 12% to 59%. Limitation of reinforcement has been principally the risk of adverse events caused by synthetic materials. Biologic and resorbable synthetic materials are valid alternatives. This study compares the host response to all these materials after hiatal hernia repair. A total of 20 Landrace pigs, underwent laparoscopic primary hiatal hernia repair and reinforced with a polypropylene mesh (PROLENE: polypropylene [PP]), an absorbable synthetic scaffold (GOREBIO-A: polyglycolic acid [PGA]), a urinary bladder matrix scaffold, (Gentrix: urinary bladder matrix [UBM]), or without reinforcement, control group (C). Animals were survived for 3 months. Endpoints included gross morphology, biomechanical testing, and histology. Pigs in PP and PGA groups showed fibrosis at the repair site, with robust adhesions. In UBM and C groups, only mild adhesions were found. Load at failure (gr) and stiffness (gr/mm) of PP were higher than C group (PP:2103 ± 548.3 versus C:951.1 ± 372.7, P = 0.02; PP:643.3 ± 301 versus C:152.6 ± 142.7, P = 0.01). PGA and UBM values for both parameters were in between PP and C samples. However, stiffness in UBM was tended to be lower than PP group, and approached a significant difference (643.3 ± 301 versus 243 ± 122.1, P = 0.0536). In UBM group, the histology resembled native tissue. By contrast, PP and PGA groups showed mononuclear infiltrates, fibroencapsulation, necrosis, remnants of mesh, and disorganized tissue that was validated with a histologic score. In this setting, UBM scaffolds showed the most appropriate features for hiatal hernia repair, recovering the tissue properties that can help reduce the possibility of early failure and prevent complications associated with the implanted material.

Comparison of in vivo remodeling of urinary bladder matrix and acellular dermal matrix in an ovine model.

AIM: Biologically derived surgical graft materials come from a variety of sources with varying mechanical properties. This study aimed to evaluate the host response and mechanical performance of two extracellular matrix devices in a large animal preclinical model. MATERIALS & METHODS: Bilateral defects were created in the fascia lata of sheep and repaired with either an acellular dermal matrix (ADM) or urinary bladder matrix (UBM). After 1 or 3 months, the repair site was explanted for histological and mechanical analysis. RESULTS & CONCLUSION: Despite pre-implantation mechanical differences, both UBM and ADM demonstrated similar mechanical performance at 3 months. However, UBM was completely remodeled into site-appropriate tissue by 3 months, while ADM showed limited tissue incorporation.

Retrorectus repair of incisional ventral hernia with urinary bladder matrix reinforcement in a long-term porcine model.

AIM: Not all biologically derived materials elicit the same host response when used for reinforcement of ventral hernia repairs. This study aimed to evaluate the remodeling characteristics of the abdominal wall following reinforcement with urinary bladder matrix (UBM) in a large animal preclinical model of ventral hernia repair. MATERIALS & METHODS: Midline defects in 36 Yucatan minipigs were reinforced with UBM-derived surgical devices using a classic Rives-Stoppa-Wantz approach, and compared with primary repair controls. After 3 or 8 months, the abdominal wall was explanted for histological and mechanical analysis. RESULTS & CONCLUSION: All UBM-derived surgical devices were completely resorbed within 8 months and facilitated deposition of vascularized, biomechanically functional connective tissue in the retrorectus plane, with no evidence of hernia formation.

Stimulation of adipogenesis of adult adipose-derived stem cells using substrates that mimic the stiffness of adipose tissue.

Biochemical and biomechanical extracellular matrix (ECM) cues have recently been shown to play a role in stimulating stem cell differentiation towards several lineages, though how they combine to induce adipogenesis has been less well studied. The objective of this study was to recapitulate both the ECM composition and mechanical properties of adipose tissue in vitro to stimulate adipogenesis of human adipose-derived stem cells (ASCs) in the absence of exogenous adipogenic growth factors and small molecules. Adipose specific ECM biochemical cues have been previously shown to influence adipogenic differentiation; however, the ability of biomechanical cues to promote adipogenesis has been less defined. Decellularized human lipoaspirate was used to functionalize polyacrylamide gels of varying stiffness to allow the cells to interact with adipose-specific ECM components. Culturing ASCs on gels that mimicked the native stiffness of adipose tissue (2 kPa) significantly upregulated adipogenic markers, in the absence of exogenous adipogenic growth factors and small molecules. As substrate stiffness increased, the cells became more spread, lost their rounded morphology, and failed to upregulate adipogenic markers. Together these data imply that as with other lineages, mechanical cues are capable of regulating adipogenesis in ASCs.

Human cardiomyogenesis and the need for systems biology analysis.

Cardiovascular disease remains the leading cause of death in the Western world and myocardial infarction is one of the primary facets of this disease. The limited natural self-renewal of cardiac muscle following injury and restricted supply of heart transplants has encouraged researchers to investigate other means to stimulate regeneration of damaged myocardium. The plasticity of stem cells toward multiple lineages offers the potential to repair the heart following injury. Embryonic stem cells have been extensively studied for their ability to differentiate into early cardiomyocytes, however, the pathway has only been partially defined and inadequate efficiency limits their clinical applicability. Some studies have shown cardiomyogenesis from adult mesenchymal stem cells, from both bone marrow and adipose tissue, but their differentiation pathway remains poorly detailed and these results remain controversial. Despite promising results using stem cells in animal models of cardiac injury, the driving mechanisms behind their differentiation down a cardiomyogenic pathway have yet to be determined. Currently, there is a paucity of information regarding cardiomyogenesis on the systemic level. Stem cell differentiation results from multiple signaling parameters operating in a tightly regulated spatiotemporal pattern. Investigating this phenomenon from a systems biology perspective could unveil the abstruse mechanisms controlling cardiomyogenesis that would otherwise require extensive in vitro testing.

Injectable hydrogel scaffold from decellularized human lipoaspirate.

Soft tissue fillers are rapidly gaining popularity for aesthetic improvements or repair of adipose tissue deficits. Several injectable biopolymers have been investigated for this purpose, but often show rapid resorption or limited adipogenesis and do not mimic the native adipose extracellular matrix (ECM). We have generated an injectable adipose matrix scaffold by efficiently removing both the cellular and lipid contents of human lipoaspirate. The decellularized material retained the complex composition of peptides and glycosaminoglycans found in native adipose ECM. This matrix can be further processed by solubilizing the extracted ECM to generate a thermally responsive hydrogel that self-assembles upon subcutaneous injection. This hydrogel also supports the growth and survival of patient matched adipose-derived stem cells in vitro. The development of an injectable hydrogel from human lipoaspirate represents a minimally invasive option for adipose tissue engineering in terms of both the collection of source material and delivery of the scaffold.