Oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS) are chronic inflammatory conditions often characterised by erosive and/or painful oral lesions that have a considerable impact on quality of life. Current treatment often necessitates the use of steroids in the form of mouthwashes, creams or ointments, but these are often ineffective due to inadequate drug contact times with the lesion. Here we evaluate the performance of novel mucoadhesive patches for targeted drug delivery. Electrospun polymeric mucoadhesive patches were produced and characterised for their physical properties and cytotoxicity before evaluation of residence time and acceptability in a human feasibility study. Clobetasol-17-propionate incorporated into the patches was released in a sustained manner in both tissue-engineered oral mucosa and ex vivo porcine mucosa. Clobetasol-17 propionate-loaded patches were further evaluated for residence time and drug release in an in vivo animal model and demonstrated prolonged adhesion and drug release at therapeutic-relevant doses and time points. These data show that electrospun patches are adherent to mucosal tissue without causing tissue damage, and can be successfully loaded with and release clinically active drugs. These patches hold great promise for the treatment of oral conditions such as OLP and RAS, and potentially many other oral lesions.

Bioactive glasses are known to stimulate bone healing, and the incorporation of strontium has the potential to increase their potency. In this study, calcium oxide in the 45S5 bioactive glass composition was partially (50%, Sr50) or fully (100%, Sr100) substituted with strontium oxide on a molar basis. The effects of the substitution on bioactive glass properties were studied, including density, solubility, and in vitro cytotoxicity. Stimulation of osteogenic differentiation was investigated using mesenchymal stromal cells obtained from rat bone marrow. Strontium substitution resulted in altered physical properties including increased solubility. Statistically significant reductions in cell viability were observed with the addition of bioactive glass powders to culture medium. Specifically, addition of ≥ 13.3 mg/ml of 45S5 bioactive glass or Sr50, or ≥ 6.7 mg/ml of Sr100, resulted in significant inhibition. Real‐time PCR analyses detected the upregulation of genes associated with osteoblastic differentiation in the presence of all bioactive glass compositions. Some genes, including Alpl and Bglap, were further stimulated in the presence of Sr50 and Sr100. It was concluded that strontium‐substituted bioactive glasses promoted osteogenesis in a differentiating bone cell culture model and, therefore, have considerable potential for use as improved bioactive glasses for bone tissue regeneration. © 2015 The Authors. Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

Oral mucosal lesions are related to several etiologies, including trauma, infection, and immunologic and neoplastic diseases. Their prevalence varies greatly depending on ethnicity, gender, and exposure to risk factors. Currently, most oral mucosal lesions are treated with creams, mouthwashes, or gels containing suitable drugs. However, topical medications may be relatively ineffective as they are removed rapidly from oral surfaces, limiting drug contact times. Systemic medications might be more effective but are associated with unacceptable off-target side effects. The aim of this study was to produce novel polymeric mucoadhesive membranes for therapeutic applications on the oral mucosa using electrospinning. Poly(vinylpyrrolidone) (PVP) and Eudragit RS100 (RS100) were used for the fabrication of membranes, whereas dextran (Dex) or poly(ethylene oxide) (PEO) particles were incorporated to enhance their mucoadhesive properties. An electrospun poly(caprolactone) (PCL) backing layer (BL) was added to create a dual-layer system. Solution properties were studied using rheometry, and membranes were characterized using differential thermal analysis and scanning electron microscopy. Solubility, surface hydrophobicity, and adhesion properties were also investigated. The solution viscosity varied depending on the composition and concentration, affecting fiber production. The addition of RS100 to PVP resulted in reduced membrane porosity and solubility, and increased surface hydrophobicity and in vitro adhesion times. Dex and PEO particles were located on the surface of the fibers. A PCL BL was successfully produced, with enhanced attachment between layers achieved through thermal treatment. PVP homopolymer membranes did not adhere to plastic or porcine mucosa, whereas PVP/RS100 membranes with and without PEO or Dex were tightly adherent. In conclusion, PVP and RS100 may be combined to tailor membrane properties. Furthermore, electrospinning facilitated the production of membranes consisting of mucoadhesive-fabricated fibers displaying increased surface area and long-lasting adhesive properties. These novel compositions exhibit great potential for the fabrication of mucoadhesive patches for therapeutic applications in oral medicine.

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Barrier membranes used for the treatment of bone tissue defects caused by periodontitis lack the ability to promote new bone tissue regeneration. However, the addition of an osteogenic component to membranes may enhance their regenerative potential. Here the manufacturing of composite membranes made of poly(caprolactone) and strontium‐substituted bioactive glass is described using the solution‐electrospinning technique, with particles located both inside and on the surface of the fibers. All membranes are characterized using scanning electron microscopy and energy dispersive X‐ray spectroscopy, and glass dissolution from within the fibers is investigated in water. In vitro material cytotoxicity is determined using a rat osteosarcoma cell line. Electrospun fibers exhibit porous surfaces and regions of increased diameter where the particles are accumulated. The glass dissolves after immersion in water, releasing dissolution products that are associated with increased pH. Further evidence suggests accelerated polymer degradation due to interactions between both components, which may provide the additional benefit of reducing the pH changes associated with glass dissolution. All compositions are biocompatible in vitro, with the exception of membranes with >50 μg of glass on their surface. In conclusion, these membranes show great potential for bone healing applications, including guided bone regeneration and scaffolds for musculoskeletal tissue engineering.

Additive manufacturing technologies enable the creation of very precise and well-defined structures that can mimic hierarchical features of natural tissues. In this article, we describe the development of a manufacturing technology platform to produce innovative biodegradable membranes that are enhanced with controlled microenvironments produced via a combination of selective laser melting techniques and conventional electrospinning. This work underpins the manufacture of a new generation of biomaterial devices that have significant potential for use as both basic research tools and components of therapeutic implants. The membranes were successfully manufactured and a total of three microenvironment designs (niches) were chosen for thorough characterisation. Scanning electron microscopy analysis demonstrated differences in fibre diameters within different areas of the niche structures as well as differences in fibre density. We also showed the potential of using the microfabricated membranes for supporting mesenchymal stromal cell culture and proliferation. We demonstrated that mesenchymal stromal cells grow and populate the membranes penetrating within the niche-like structures. These findings demonstrate the creation of a very versatile tool that can be used in a variety of tissue regeneration applications including bone healing.

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This is a repository copy of Novel bilayer mucoadhesive patches for delivery of clobetasol-17-propionate to the oral mucosa to treat oral lichen planus; an in vitro and in vivo evaluation.