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Polymer-based Instructive Scaffolds for Regenerative Medicine

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A special issue of Materials (ISSN 1996-1944). This special issue belongs to the section "Biomaterials".

Deadline for manuscript submissions: closed (15 July 2019) | Viewed by 40091

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Special Issue Editors

Prof. Dr. Silvia Farè

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Guest Editor

Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, 20133 Milan, Italy
Interests: polymer synthesis and characterization; biomimetic polymers; synthetic and natural polymers; smart polymers and stimuli-responsive hydrogels; cell-biomaterial interactions; microstructured 2D and 3D structure for regenerative medicine; electrospinning; 3D printing and bioprinting

Dr. Lorenza Draghi

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Guest Editor

Politecnico di Milano, Department of Chemistry, Materials and Chemical Engineering “G. Natta”, Piazza Leonardo da Vinci 32, 20133 Milan, Italy
Interests: biomaterials; scaffold fabrication; regenerative medicine; natural polymers

Special Issue Information

Dear Colleagues,

Since its inception, a few decades ago, regenerative medicine has shown an impressive evolution and a broad range of therapeutic strategies can be now encountered at all stages of investigation.

The considerable, interdisciplinary effort in this field has led to an increasingly refined understanding of the mechanisms involved in tissue regeneration and of the factors that play a role in regulating the process. Among them, scaffolds and carrier materials are critical in most applications.

Besides the bare physical support, scaffold materials and architectures can now be designed to provide specific cues for directing cell fate and guide tissue regeneration. Polymers containing specific adhesion sequences, micro- and nano patterning, and hydrogels loaded with biologically active molecules are all common strategies along this track.

In this scenario, this Special Issue focuses on advanced materials, fabrication and modification techniques enabling the preparation of sophisticated scaffolds capable to promote optimal regenerative responses from cells and enhance the regeneration processes to, ultimately, support clinical translation of innovative approaches.

We kindly invite you to submit a manuscript(s) for this Special Issue. Full papers, communications, and reviews are all welcome.

Prof. Silvia Farè
Dr. Lorenza Draghi
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Materials is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

instructive scaffolds
natural polymers
bioconiugated polymers
hydrogels
additive manufacturing
bioprinting
electrospinning
micro- and nano-patterning

Published Papers (7 papers)

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Research

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19 pages, 3771 KiB

Open AccessArticle

Sodium Alginate/Gelatine Hydrogels for Direct Bioprinting—The Effect of Composition Selection and Applied Solvents on the Bioink Properties

by Dorota Bociaga, Mateusz Bartniak, Jacek Grabarczyk and Karolina Przybyszewska

Materials 2019, 12(17), 2669; https://doi.org/10.3390/ma12172669 - 22 Aug 2019

Cited by 59 | Viewed by 5383

Abstract

Hydrogels tested and evaluated in this study were developed for the possibility of their use as the bioinks for 3D direct bioprinting. Procedures for preparation and sterilization of hydrogels and the speed of the bioprinting were developed. Sodium alginate gelatine hydrogels were characterized in terms of printability, mechanical, and biological properties (viability, proliferation ability, biocompatibility). A hydrogel with the best properties was selected to carry out direct bioprinting tests in order to determine the parameters of the bioink, adapted to print with use of the designed and constructed bioprinter and provide the best conditions for cell growth. The obtained results showed the ability to control mechanical properties, biological response, and degradation rate of hydrogels through the use of various solvents. The use of a dedicated culture medium as a solvent for the preparation of a bioink, containing the predicted cell line, increases the proliferation of these cells. Modification of the percentage of individual components of the hydrogel gives the possibility of a controlled degradation process, which, in the case of printing of temporary medical devices, is a very important parameter for the hydrogels’ usage possibility—both in terms of tissue engineering and printing of tissue elements replacement, implants, and organs. Full article

(This article belongs to the Special Issue Polymer-based Instructive Scaffolds for Regenerative Medicine)

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24 pages, 4867 KiB

Open AccessFeature PaperArticle

A Novel Bilayer Polycaprolactone Membrane for Guided Bone Regeneration: Combining Electrospinning and Emulsion Templating

by Betül Aldemir Dikici, Serkan Dikici, Gwendolen C. Reilly, Sheila MacNeil and Frederik Claeyssens

Materials 2019, 12(16), 2643; https://doi.org/10.3390/ma12162643 - 20 Aug 2019

Cited by 71 | Viewed by 7031

Abstract

Guided bone regeneration is a common dental implant treatment where a barrier membrane (BM) is used between epithelial tissue and bone or bone graft to prevent the invasion of the fast-proliferating epithelial cells into the defect site to be able to preserve a space for infiltration of slower-growing bone cells into the periodontal defect site. In this study, a bilayer polycaprolactone (PCL) BM was developed by combining electrospinning and emulsion templating techniques. First, a 250 µm thick polymerised high internal phase emulsion (polyHIPE) made of photocurable PCL was manufactured and treated with air plasma, which was shown to enhance the cellular infiltration. Then, four solvent compositions were investigated to find the best composition for electrospinning a nanofibrous PCL barrier layer on PCL polyHIPE. The biocompatibility and the barrier properties of the electrospun layer were demonstrated over four weeks in vitro by histological staining. Following in vitro assessment of cell viability and cell migration, cell infiltration and the potential of PCL polyHIPE for supporting blood vessel ingrowth were further investigated using an ex-ovo chick chorioallantoic membrane assay. Our results demonstrated that the nanofibrous PCL electrospun layer was capable of limiting cell infiltration for at least four weeks, while PCL polyHIPE supported cell infiltration, calcium and mineral deposition of bone cells, and blood vessel ingrowth through pores. Full article

(This article belongs to the Special Issue Polymer-based Instructive Scaffolds for Regenerative Medicine)

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13 pages, 1940 KiB

Open AccessArticle

Injectable Scaffolds Enriched with Silver to Inhibit Bacterial Invasion in Tissue Regeneration

by Chiara Ceresa, Letizia Fracchia, Alice Marchetti, Maurizio Rinaldi and Michela Bosetti

Materials 2019, 12(12), 1931; https://doi.org/10.3390/ma12121931 - 15 Jun 2019

Cited by 12 | Viewed by 2555

Abstract

During wound healing, bacterial infections may prolong skin regeneration and tissue repair, causing delayed or incomplete healing. The therapeutic strategies currently used include general therapeutic modes, growth factors, skin substitutes, matrices and/or cell therapy. Among recent technologies, wound dressing materials comprising silver nitrate or silver sulfadiazine as the antimicrobial agent are widespread, despite their known cytotoxicity. The aim of this work was to develop and evaluate the efficacy of gelatinous injectable biomaterials composed of collagen and alginates, enriched with silver against bacterial pathogens commonly involved in wound infections. To reduce cytotoxicity, silver was used as lactate and saccharinated salts. Results show that silver-enriched beads were effective against both Gram-positive and Gram-negative strains in a concentration-dependent manner. Silver addition was more active against Staphylococcus epidermidis than against Pseudomonas aeruginosa. The antibacterial activity was localized only in the area of contact with the beads at concentrations lower than 0.3 mM, whereas at higher concentrations a larger inhibition halo was observed. No cytotoxic effect on eukaryotic cells was seen both testing the materials’ extracts or the Ag-doped beads in contact tests. These results, although preliminary, suggest that these scaffolds are a promising approach for realizing injectable or spreadable functional biomaterials with antibacterial activity for applications in wound management. Full article

(This article belongs to the Special Issue Polymer-based Instructive Scaffolds for Regenerative Medicine)

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10 pages, 2089 KiB

Open AccessArticle

Fabrication and Characterization of Bioresorbable Drug-coated Porous Scaffolds for Vascular Tissue Engineering

by Jueun Kim, Su A. Park, Jei Kim and Jaejong Lee

Materials 2019, 12(9), 1438; https://doi.org/10.3390/ma12091438 - 02 May 2019

Cited by 12 | Viewed by 2921

Abstract

Bioresorbable polymers have been studied for several decades as attractive candidates for promoting the advancement of medical science and bio-technology in modern society. In particular, with a well-defined architecture, bioresorbable polymers have prominent advantages over their bulk counterparts for applications in biomedical and implant devices, such as cell delivery, scaffolds for tissue engineering, and hydrogels as well as in the pharmaceutical fields. Biocompatible implant devices based on bioresorbable materials (for instance, bioresorbable polymers that combine the unique advantages of biocompability and easy handling) have emerged as a highly active field due to their promising applications in artificial implant systems and biomedical devices. In this paper, we report an approach to fabricate porous polycaprolactone (PCL) scaffolds using a 3D printing system. And its surface was treated to a hydrophilic surface using plasma treatment. Then, the aspirin and atorvastatin calcium salt mixture was dip coated onto the surface. The drug coating technology was used to deposit the drug material onto the scaffold surface. Our porous PCL scaffold was coated with aspirin and atorvastatin calcium salt to reduce the blood LDL cholesterol and restenosis. These results suggest that our approach may provide a promising scaffold for developing bioresorbable drug-delivery-biomaterials. We further demonstrate that our bioresorbable medical device can be used as vascular scaffolds to provide a wide range of applications for the design of medical devices. Full article

(This article belongs to the Special Issue Polymer-based Instructive Scaffolds for Regenerative Medicine)

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19 pages, 8954 KiB

Open AccessArticle

Application of a Bioactive/Bioresorbable Three-Dimensional Porous Uncalcined and Unsintered Hydroxyapatite/Poly-d/l-lactide Composite with Human Mesenchymal Stem Cells for Bone Regeneration in Maxillofacial Surgery: A Pilot Animal Study

by Jingjing Sha, Takahiro Kanno, Kenichi Miyamoto, Yunpeng Bai, Katsumi Hideshima and Yumi Matsuzaki

Materials 2019, 12(5), 705; https://doi.org/10.3390/ma12050705 - 27 Feb 2019

Cited by 17 | Viewed by 3040

Abstract

A novel three-dimensional (3D) porous uncalcined and unsintered hydroxyapatite/poly-d/l-lactide (3D-HA/PDLLA) composite demonstrated superior biocompatibility, osteoconductivity, biodegradability, and plasticity, thereby enabling complex maxillofacial defect reconstruction. Mesenchymal stem cells (MSCs)—a type of adult stem cell—have a multipotent ability to differentiate into chondrocytes, adipocytes, and osteocytes. In a previous study, we found that CD90 (Thy-1, cluster of differentiation 90) and CD271 (low-affinity nerve growth factor receptor) double-positive cell populations from human bone marrow had high proliferative ability and differentiation capacity in vitro. In the present study, we investigated the utility of bone regeneration therapy using implantation of 3D-HA/PDLLA loaded with human MSCs (hMSCs) in mandibular critical defect rats. Microcomputed tomography (Micro-CT) indicated that implantation of a 3D-HA/PDLLA-hMSC composite scaffold improved the ability to achieve bone regeneration compared with 3D-HA/PDLLA alone. Compared to the sufficient blood supply in the mandibular defection superior side, a lack of blood supply in the inferior side caused delayed healing. The use of Villanueva Goldner staining (VG staining) revealed the gradual progression of the nucleated cells and new bone from the scaffold border into the central pores, indicating that 3D-HA/PDLLA loaded with hMSCs had good osteoconductivity and an adequate blood supply. These results further demonstrated that the 3D-HA/PDLLA-hMSC composite scaffold was an effective bone regenerative method for maxillofacial boney defect reconstruction. Full article

(This article belongs to the Special Issue Polymer-based Instructive Scaffolds for Regenerative Medicine)

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Review

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23 pages, 3438 KiB

Open AccessReview

Cross-Linking Strategies for Electrospun Gelatin Scaffolds

by Chiara Emma Campiglio, Nicola Contessi Negrini, Silvia Farè and Lorenza Draghi

Materials 2019, 12(15), 2476; https://doi.org/10.3390/ma12152476 - 04 Aug 2019

Cited by 158 | Viewed by 13100

Abstract

Electrospinning is an exceptional technology to fabricate sub-micrometric fiber scaffolds for regenerative medicine applications and to mimic the morphology and the chemistry of the natural extracellular matrix (ECM). Although most synthetic and natural polymers can be electrospun, gelatin frequently represents a material of choice due to the presence of cell-interactive motifs, its wide availability, low cost, easy processability, and biodegradability. However, cross-linking is required to stabilize the structure of the electrospun matrices and avoid gelatin dissolution at body temperature. Different physical and chemical cross-linking protocols have been described to improve electrospun gelatin stability and to preserve the morphological fibrous arrangement of the electrospun gelatin scaffolds. Here, we review the main current strategies. For each method, the cross-linking mechanism and its efficiency, the influence of electrospinning parameters, and the resulting fiber morphology are considered. The main drawbacks as well as the open challenges are also discussed. Full article

(This article belongs to the Special Issue Polymer-based Instructive Scaffolds for Regenerative Medicine)

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18 pages, 960 KiB

Open AccessFeature PaperReview

Polymer-Based Instructive Scaffolds for Endodontic Regeneration

by Naimah Zein, Ezeddine Harmouch, Jean-Christophe Lutz, Gabriel Fernandez De Grado, Sabine Kuchler-Bopp, François Clauss, Damien Offner, Guoqiang Hua, Nadia Benkirane-Jessel and Florence Fioretti

Materials 2019, 12(15), 2347; https://doi.org/10.3390/ma12152347 - 24 Jul 2019

Cited by 39 | Viewed by 5553

Abstract

The challenge of endodontic regeneration is modulated by clinical conditions which determine five kinds of tissue requirements: pulp connective-tissue formation, dentin formation, revascularization, reinnervation and radicular edification. Polymer scaffolds constitute keystone of the different endodontic regenerative strategies. Indeed, scaffolds are crucial for carrying active molecules and competent cells which optimize the regeneration. Hydrogels are very beneficial for controlling viscosity and porosity of endodontic scaffolds. The nanofibrous and microporous scaffolds mimicking extracellular matrix are also of great interest for promoting dentin-pulp formation. Two main types of polymer scaffolds are highlighted: collagen and fibrin. Collagen scaffolds which are similar to native pulp tissue, are adequate for pulp connective tissue formation. Functionnalization by active biomolecules as BMP, SDF-1, G-CSF enhances their properties. Fibrin or PRF scaffolds present the advantage of promoting stem cell differentiation and concomitant revascularisation. The choice of the type of polymers (polypeptide, PCL, chitosan) can depend on its ability to deliver the active biomolecule or to build as suitable hydrogel as possible. Since 2010s, proposals to associate different types of polymers in a same scaffold have emerged for adding advantages or for offsetting a disadvantage of a polymer. Further works would study the synergetic effects of different innovative polymers composition. Full article

(This article belongs to the Special Issue Polymer-based Instructive Scaffolds for Regenerative Medicine)

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