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      Medical-grade polycaprolactone scaffolds made by melt electrospinning writing for oral bone regeneration – a pilot study in vitro

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          Abstract

          Background

          The spectrum of indications for the use of membranes and scaffolds in the field of oral and maxillofacial surgery includes, amongst others, guided bone regeneration (GBR). Currently available membrane systems face certain disadvantages such as difficult clinical handling, inconsistent degradation, undirected cell growth and a lack of stability that often complicate their application. Therefore, new membranes which can overcome these issues are of great interest in this field.

          Methods

          In this pilot study, we investigated polycaprolactone (PCL) scaffolds intended to enhance oral wound healing by means of melt electrospinning writing (MEW), which allowed for three-dimensional (3D) printing of micron scale fibers and very exact fiber placement. A singular set of box-shaped scaffolds of different sizes consisting of medical-grade PCL was examined and the scaffolds’ morphology was evaluated via scanning electron microscopy (SEM). Each prototype sample with box sizes of 225 μm, 300 μm, 375 μm, 450 μm and 500 μm was assessed for cytotoxicity and cell growth by seeding each scaffold with human osteoblast-like cell line MG63.

          Results

          All scaffolds demonstrated good cytocompatibility according to cell viability, protein concentration, and cell number. SEM analysis revealed an exact fiber placement of the MEW scaffolds and the growth of viable MG63 cells on them. For the examined box-shaped scaffolds with pore sizes between 225 μm and 500 μm, a preferred box size for initial osteoblast attachment could not be found.

          Conclusions

          These well-defined 3D scaffolds consisting of medical-grade materials optimized for cell attachment and cell growth hold the key to a promising new approach in GBR in oral and maxillofacial surgery.

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          Most cited references28

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          The effect of pore size on cell adhesion in collagen-GAG scaffolds.

          The biological activity of scaffolds used in tissue engineering applications hypothetically depends on the density of available ligands, scaffold sites at which specific cell binding occurs. Ligand density is characterized by the composition of the scaffold, which defines the surface density of ligands, and by the specific surface area of the scaffold, which defines the total surface of the structure exposed to the cells. It has been previously shown that collagen-glycosaminoglycan (CG) scaffolds used for studies of skin regeneration were inactive when the mean pore size was either lower than 20 microm or higher than 120 microm (Proc. Natl. Acad. Sci., USA 86(3) (1989) 933). To study the relationship between cell attachment and viability in scaffolds and the scaffold structure, CG scaffolds with a constant composition and solid volume fraction (0.005), but with four different pore sizes corresponding to four levels of specific surface area were manufactured using a lyophilization technique. MC3T3-E1 mouse clonal osteogenic cells were seeded onto the four scaffold types and maintained in culture. At the experimental end point (24 or 48 h), the remaining viable cells were counted to determine the percent cell attachment. A significant difference in viable cell attachment was observed in scaffolds with different mean pore sizes after 24 and 48 h; however, there was no significant change in cell attachment between 24 and 48 h for any group. The fraction of viable cells attached to the CG scaffold decreased with increasing mean pore size, increasing linearly (R2 = 0.95, 0.91 at 24 and 48 h, respectively) with the specific surface area of the scaffold. The strong correlation between the scaffold specific surface area and cell attachment indicates that cell attachment and viability are primarily influenced by scaffold specific surface area over this range (95.9-150.5 microm) of pore sizes for MC3T3 cells.
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            Collagen membranes: a review.

            Collagen materials have been utilized in medicine and dentistry because of their proven biocompatability and capability of promoting wound healing. For guided tissue regeneration (GTR) procedures, collagen membranes have been shown to be comparable to non-absorbable membranes with regard to probing depth reduction, clinical attachment gain, and percent of bone fill. Although these membranes are absorbable, collagen membranes have been demonstrated to prevent epithelial down-growth along the root surfaces during the early phase of wound healing. The use of grafting material in combination with collagen membranes seems to improve clinical outcomes for furcation, but not intrabony, defects when compared to the use of membranes alone. Recently, collagen materials have also been applied in guided bone regeneration (GBR) and root coverage procedures with comparable success rates to non-absorbable expanded polytetrafluoroethylene (ePTFE) membranes and conventional subepithelial connective tissue grafts, respectively. Long-term clinical trials are still needed to further evaluate the benefits of collagen membranes in periodontal and peri-implant defects. This article will review the rationale for each indication and its related literature, both in vitro and in vivo studies. The properties that make collagen membranes attractive for use in regenerative therapy will be addressed. In addition, varieties of cross-linking techniques utilized to retard the degradation rate of collagen membranes will be discussed.
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              Role of pore size and morphology in musculo-skeletal tissue regeneration.

              Biomaterials in the form of scaffolds hold great promise in the regeneration of diseased tissues. The scaffolds stimulate cellular adhesion, proliferation and differentiation. While the scaffold composition will dictate their biocompatibility, their porosity plays a key role in allowing proper cell penetration, nutrient diffusion as well as bone ingrowth. Porous scaffolds are processed with the help of a wide variety of techniques. Designing scaffolds with the appropriate porosity is a complex issue since this may jeopardize other physico-chemical properties. From a macroscopic point of view, parameters such as the overall architecture, pore morphology, interconnectivity and pore size distribution, have unique roles in allowing bone ingrowth to take place. From a microscopic perspective, the adsorption and retention of proteins in the microporosities of the material will dictate the subsequent cell adhesion. Therefore, the microstructure of the substrate can determine cell proliferation as well as the expression of specific osteogenic genes. This review aims at discussing the effect of micro- and macroporosity on the physico-chemical and biological properties of scaffolds for musculo-skeletal tissue regeneration.
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                Author and article information

                Contributors
                +49 931 201 74190 , fuchs_a2@ukw.de
                moataz.youssef@fmz.uni-wuerzburg.de
                seher_a@ukw.de
                gernot.hochleitner@fmz.uni-wuerzburg.de
                paul.dalton@fmz.uni-wuerzburg.de
                hartmann_s2@ukw.de
                brands_r@ukw.de
                mueller_u2@ukw.de
                linz_c@ukw.de
                Journal
                BMC Oral Health
                BMC Oral Health
                BMC Oral Health
                BioMed Central (London )
                1472-6831
                1 February 2019
                1 February 2019
                2019
                : 19
                : 28
                Affiliations
                [1 ]ISNI 0000 0001 1378 7891, GRID grid.411760.5, Department of Oral and Maxillofacial Plastic Surgery, , University Hospital Würzburg, ; Pleicherwall 2, 97080 Würzburg, Germany
                [2 ]ISNI 0000 0001 1378 7891, GRID grid.411760.5, Department for Functional Materials in Medicine and Dentistry, , University Hospital Würzburg, ; Pleicherwall 2, 97080 Würzburg, Germany
                [3 ]ISNI 0000 0001 1378 7891, GRID grid.411760.5, Interdisciplinary Center for Clinical Research, , University Hospital Würzburg, ; Josef-Schneider-Straße 2, 97070 Würzburg, Germany
                Article
                717
                10.1186/s12903-019-0717-5
                6359770
                30709394
                5f73402a-2295-4fc3-8912-25bd54a06fc2
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 9 August 2018
                : 21 January 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004608, Natural Science Foundation of Jiangsu Province;
                Award ID: BK20160064
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 31802222
                Funded by: National Key Research and Development Program of China
                Award ID: 2017YFD0500804
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Dentistry
                melt electrospinning writing,polycaprolactone,scaffold,guided bone regeneration
                Dentistry
                melt electrospinning writing, polycaprolactone, scaffold, guided bone regeneration

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