Sabiniano Roman

Comparison of candidate scaffolds for tissue engineering for stress urinary incontinence and pelvic organ prolapse repair

To identify candidate materials which have sufficient potential to be taken forward for an in vivo tissue‐engineering approach to restoring the tissue structure of the pelvic floor in women with stress urinary incontinence (SUI) or pelvic organ prolapse (POP).

Developing a tissue engineered repair material for treatment of stress urinary incontinence and pelvic organ prolapse—which cell source?

Synthetic non‐absorbable meshes are widely used to augment surgical repair of stress urinary incontinence (SUI) and pelvic organ prolapse (POP); however, there is growing concern such meshes are associated with serious complications. This study compares the potential of two autologous cell sources for attachment and extra‐cellular matrix (ECM) production on a biodegradable scaffold to develop tissue engineered repair material (TERM).

Biomimetic poly(glycerol sebacate)/poly(l-lactic acid) blend scaffolds for adipose tissue engineering

Large three-dimensional poly(glycerol sebacate) (PGS)/poly(l-lactic acid) (PLLA) scaffolds with similar bulk mechanical properties to native low and high stress adapted adipose tissue were fabricated via a freeze-drying and a subsequent curing process. PGS/PLLA scaffolds containing 73vol.% PGS were prepared using two different organic solvents, resulting in highly interconnected open-pore structures with porosities and pore sizes in the range of 91-92% and 109-141μm, respectively. Scanning electron microscopic analysis indicated that the scaffolds featured different microstructure characteristics, depending on the organic solvent in use. The PGS/PLLA scaffolds had a tensile Youngs modulus of 0.030MPa, tensile strength of 0.007MPa, elongation at the maximum stress of 25% and full shape recovery capability upon release of the compressive load. In vitro degradation tests presented mass losses of 11-16% and 54-55% without and with the presence of lipase enzyme in 31days, respectively. In vitro cell tests exhibited clear evidence that the PGS/PLLA scaffolds prepared with 1,4-dioxane as the solvent are suitable for culture of adipose derived stem cells. Compared to pristine PLLA scaffolds prepared with the same procedure, these scaffolds provided favourable porous microstructures, good hydrophilic characteristics, and appropriate mechanical properties for soft tissue applications, as well as enhanced scaffold cell penetration and tissue in-growth characteristics. This work demonstrates that the PGS/PLLA scaffolds have potential for applications in adipose tissue engineering.

Brown adipose tissue and novel therapeutic approaches to treat metabolic disorders

In humans, 2 functionally different types of adipose tissue coexist: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is involved in energy storage, whereas BAT is involved in energy expenditure. Increased amounts of WAT may contribute to the development of metabolic disorders, such as obesity-associated type 2 diabetes mellitus and cardiovascular diseases. In contrast, the thermogenic function of BAT allows high consumption of fatty acids because of the activity of uncoupling protein 1 in the internal mitochondrial membrane. Interestingly, obesity reduction and insulin sensitization have been achieved by BAT activation-regeneration in animal models. This review describes the origin, function, and differentiation mechanisms of BAT to identify new therapeutic strategies for the treatment of metabolic disorders related to obesity. On the basis of the animal studies, novel approaches for BAT regeneration combining stem cells from the adipose tissue with active components, such as melatonin, may have potential for the treatment of metabolic disorders in humans.

Evaluating Alternative Materials for the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse: A Comparison of the In Vivo Response to Meshes Implanted in Rabbits.

PURPOSE Serious complications can develop with the mesh implants used for stress urinary incontinence and pelvic organ prolapse surgery. We evaluated 2 materials currently in clinical use and 2 alternative materials using a rabbit abdominal model to assess host response and biomechanical properties of the materials before and after implantation. MATERIALS AND METHODS Poly-L-lactic acid and polyurethane meshes were electrospun to be compared to commercially available polypropylene and polyvinylidene fluoride meshes. A total of 40 immunocompetent full-thickness abdominal wall defect rabbit models were used, including 8 in each of the poly-L-lactic acid, polyurethane, polyvinylidene fluoride and polypropylene experimental groups, and sham controls. Two 20 mm defects were created per animal and primarily repaired. The experimental groups then underwent onlay of each repair material while sham controls did not. Four rabbits per group were sacrificed at days 30 and 90. Abdominal wall specimens containing the defect with or without repair material were explanted to be assessed by histology (hematoxylin and eosin staining, and immunohistochemistry) and biomechanical testing at 30 and 90 days. RESULTS At 90 days of implantation tissues repaired with all 4 materials showed biomechanical properties without significant differences. However, polypropylene and polyvinylidene fluoride meshes demonstrated a sustained chronic inflammatory response profile by 90 days. In contrast, poly-L-lactic acid and polyurethane meshes integrated well into host tissues with a decreased inflammatory response, indicative of constructive remodeling. CONCLUSIONS Poly-L-lactic acid and polyurethane alternative materials achieved better host integration in rabbit models than current synthetic repair materials.

Biodegradable and conductive chitosan–graphene quantum dot nanocomposite microneedles for delivery of both small and large molecular weight therapeutics

Biodegradable microneedles for electrically-stimulated and tracked transdermal drug delivery were created from a nanocomposite of biocompatible, biodegradable chitosan and photoluminescent, electrically conductive graphene quantum dots (GQDs). The morphology, photoluminescent properties, cell viability and cell fluorescent imaging capability of GQDs were evaluated, showing that the nanoparticles possess low cytotoxicity and fluoresce blue under UV light, allowing for potential tracking of the drug bound onto GQDs by in vivo fluorescent imaging. The structure, crystallinity, electrical, mechanical and biodegradation properties of chitosan–GQD nanocomposites were characterised. The results show the introduction of 0.25–2 wt% GQDs into chitosan considerably improves electrical conductivity, whilst maintaining similar mechanical properties and biodegradation rate at 1 wt% GQDs. The microneedle arrays prepared from the chitosan–1 wt% GQD nanocomposite are strong enough to withstand the force of insertion into the body. The nanocomposite microneedles containing drug-laden GQDs exhibit enhanced drug release behaviour for a small molecular weight model drug compared to pristine chitosan microneedles. They also enable the release of a large molecular weight model drug through iontophoresis, which is otherwise not possible under passive diffusion conditions. These novel multifunctional nanocomposites provide a universal platform for iontophoretic and tracked delivery of both small and large molecular weight therapeutics.

Thermoresponsive, stretchable, biodegradable and biocompatible poly(glycerol sebacate)-based polyurethane hydrogels

Thermoresponsive, stretchable, biodegradable and biocompatible polyester-based polyurethane (PEU) hydrogels, based on poly(glycerol sebacate) pre-polymer and poly(ethylene glycol)s of different molecular masses were synthesized by a facile solvent-based two-step method. The chemical and physical characteristics of the PEU hydrogels are tunable, enabling the design of various negatively thermosensitive, mechanically stable and biodegradable systems. The PEU hydrogels demonstrate reversible responses to a change in medium temperature from 5 °C to 37 °C, with the swelling ratio at equilibrium varying from 499% to 12%. The hydrogels have a tensile Youngs modulus, ultimate tensile strength and elongation at break in the range of 0.02–0.20 MPa, 0.05–0.47 MPa and 426–623%, respectively, and show high stretchability and full shape recovery after compression. These are similar to the mechanical properties of adipose tissues. In vitro degradation tests show mass losses of 8.7–16.3% and 10.7–20.7% without and with the presence of lipase enzyme for 31 days, respectively. In vitro cell tests show clear evidence that some of the PEU hydrogels are suitable for culturing adipose-derived stem cells and dermal fibroblasts and hence for future soft tissue regeneration. The functionalities of the PEU hydrogels were also evaluated for potential applications in drug delivery, thermal actuation and ultralow power generation. The results demonstrate the versatility of these PEU hydrogels for a variety of biomedical and engineering applications.

An anatomical study of porcine peripheral nerve and its potential use in nerve tissue engineering

Current nerve tissue engineering applications are adopting xenogeneic nerve tissue as potential nerve grafts to help aid nerve regeneration. However, there is little literature that describes the exact location, anatomy and physiology of these nerves to highlight their potential as a donor graft. The aim of this study was to identify and characterise the structural and extracellular matrix (ECM) components of porcine peripheral nerves in the hind leg. Methods included the dissection of porcine nerves, localisation, characterisation and quantification of the ECM components and identification of nerve cells. Results showed a noticeable variance between porcine and rat nerve (a commonly studied species) in terms of fascicle number. The study also revealed that when porcine peripheral nerves branch, a decrease in fascicle number and size was evident. Porcine ECM and nerve fascicles were found to be predominately comprised of collagen together with glycosaminoglycans, laminin and fibronectin. Immunolabelling for nerve growth factor receptor p75 also revealed the localisation of Schwann cells around and inside the fascicles. In conclusion, it is shown that porcine peripheral nerves possess a microstructure similar to that found in rat, and is not dissimilar to human. This finding could extend to the suggestion that due to the similarities in anatomy to human nerve, porcine nerves may have utility as a nerve graft providing guidance and support to regenerating axons.

Production of ascorbic acid releasing biomaterials for pelvic floor repair

Graphical abstract

Developing repair materials for stress urinary incontinence to withstand dynamic distension

Background Polypropylene mesh used as a mid-urethral sling is associated with severe clinical complications in a significant minority of patients. Current in vitro mechanical testing shows that polypropylene responds inadequately to mechanical distension and is also poor at supporting cell proliferation. Aims and Objectives Our objective therefore is to produce materials with more appropriate mechanical properties for use as a sling material but which can also support cell integration. Methods Scaffolds of two polyurethanes (PU), poly-L-lactic acid (PLA) and co-polymers of the two were produced by electrospinning. Mechanical properties of materials were assessed and compared to polypropylene. The interaction of adipose derived stem cells (ADSC) with the scaffolds was also assessed. Uniaxial tensiometry of scaffolds was performed before and after seven days of cyclical distension. Cell penetration (using DAPI and a fluorescent red cell tracker dye), viability (AlamarBlue assay) and total collagen production (Sirius red assay) were measured for ADSC cultured on scaffolds. Results Polypropylene was stronger than polyurethanes and PLA. However, polypropylene mesh deformed plastically after 7 days of sustained cyclical distention, while polyurethanes maintained their elasticity. Scaffolds of PU containing PLA were weaker and stiffer than PU or polypropylene but were significantly better than PU scaffolds alone at supporting ADSC. Conclusions Therefore, prolonged mechanical distension in vitro causes polypropylene to fail. Materials with more appropriate mechanical properties for use as sling materials can be produced using PU. Combining PLA with PU greatly improves interaction of cells with this material.