Publications by authors named "Martin E Santocildes-Romero"

4 Publications

  • Page 1 of 1

Incorporation of lysozyme into a mucoadhesive electrospun patch for rapid protein delivery to the oral mucosa.

Mater Sci Eng C Mater Biol Appl 2020 Jul 1;112:110917. Epub 2020 Apr 1.

Department of Chemistry, Brook Hill, University of Sheffield, Sheffield S3 7HF, UK.

The delivery of biopharmaceuticals to the oral mucosa offers a range of potential applications including antimicrobial peptides to treat resistant infections, growth factors for tissue regeneration, or as an alternative to injections for systemic delivery. Existing formulations targeting this site are typically non-specific and provide little control over dose. To address this, an electrospun dual-layer mucoadhesive patch was investigated for protein delivery to the oral mucosa. Lysozyme was used as a model antimicrobial protein and incorporated into poly(vinylpyrrolidone)/Eudragit RS100 polymer nanofibers using electrospinning from an ethanol/water mixture. The resulting fibrous membranes released the protein at a clinically desirable rate, reaching 90 ± 13% cumulative release after 2 h. Dual fluorescent fibre labelling and confocal microscopy demonstrated the homogeneity of lysozyme and polymer distribution. High encapsulation efficiency and preservation of enzyme activity were achieved (93.4 ± 7.0% and 96.1 ± 3.3% respectively). The released lysozyme inhibited the growth of the oral bacterium Streptococcus ratti, providing further evidence of retention of biological activity and illustrating a potential application for treating and preventing oral infections. An additional protective poly(caprolactone) backing layer was introduced to promote unidirectional delivery, without loss of enzyme activity, and the resulting dual-layer patches displayed long residence times using an in vitro test, showing that the adhesive properties were maintained. This study demonstrates that the drug delivery system has great potential for the delivery of therapeutic proteins to the oral mucosa.
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http://dx.doi.org/10.1016/j.msec.2020.110917DOI Listing
July 2020

Selective laser melting-enabled electrospinning: Introducing complexity within electrospun membranes.

Proc Inst Mech Eng H 2017 Jun;231(6):565-574

Bioengineering and Health Technologies Group, The School of Clinical Dentistry, The University of Sheffield, Sheffield, UK.

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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http://dx.doi.org/10.1177/0954411917690182DOI Listing
June 2017

Fabrication of Electrospun Mucoadhesive Membranes for Therapeutic Applications in Oral Medicine.

ACS Appl Mater Interfaces 2017 Apr 24;9(13):11557-11567. Epub 2017 Mar 24.

School of Clinical Dentistry, University of Sheffield , 19 Claremont Crescent, S10 2TA Sheffield, U.K.

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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http://dx.doi.org/10.1021/acsami.7b02337DOI Listing
April 2017

The osteogenic response of mesenchymal stromal cells to strontium-substituted bioactive glasses.

J Tissue Eng Regen Med 2015 May 11;9(5):619-31. Epub 2015 Mar 11.

School of Clinical Dentistry, University of Sheffield, UK.

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.
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http://dx.doi.org/10.1002/term.2003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053305PMC
May 2015
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