Special Issue "Advance of Polymers Applied to Biomedical Applications: Cell Scaffolds"

A special issue of Polymers (ISSN 2073-4360).

Deadline for manuscript submissions: closed (30 June 2017)

Special Issue Editors

Guest Editor
Prof. Dr. Insung S. Choi

Department of Chemistry, KAIST, 291 College Road, Yuseong-gu, Daejeon 34141, Korea
Website | E-Mail
Interests: cell-surface engineering; cell-material interfaces; biomimetic chemistry
Guest Editor
Prof. Dr. João F. Mano

Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal
Website | E-Mail
Phone: +351 234 370 733
Fax: +351 253 510 909
Interests: biomaterials; tissue engineering; controlled delivery of bioactive molecules; natural-based biodegradable polymers; biomimetic and nano/micro-technology approaches

Special Issue Information

Dear Colleagues,

Cells in vivo sense and respond to signals from the outside environment (e.g., other cells and extracellular matrices) for their orchestrated behavior and function. The signals come in and out in various forms, including biochemical, electrochemical, structural, and mechanical signals. Since the pioneering work by Langer and Vacanti, in vitro mimicry of the juxtacrine interactions has been achieved mainly through the use of polymers in regenerative medicine and cell therapy. The polymers act as 3D or semi-3D scaffolds for cells, on which the cells grow and proliferate.

The primary function of polymeric scaffolds was initially structural, providing the physical sites for cell adhesion and growth in a 3D form. However, scientific and technological developments have advanced to enable the manipulation of cell behavior and function, ultimately controlling cell fate, by the use of polymers, including supramolecular hydrogels. For example, as a cell scaffold, mucin-mimetic synthetic diblock copolymers have the capacity to hold human pluripotent stem cells in the quiescent G0 state in vitro, while maintaining their viability and pluripotency; Polymeric surfaces with specific topographical and chemical features direct stem cell differentiation and spacial organization; Pericellular hydrogels inhibit only cancer cells by cancer cell-specific enzymatic reactions; Individual cells are coated with polymers, and 3D cellular aggregates are formed in a controlled manner by biospecific interactions; Enzymatic reactions are utilized for the in situ formation of polymeric sheaths on cells; Microfluidic fabrication is used for programmed cell immobilization in the polymer scaffolds; And polymer-based cell-surface engineering is used for controlling cellular activities at the single-cell level. Technological advances, such as the development of 3D bioprinting, also allow for the fabrication of cellular hybrid devices wtih high geometrical control of cell positioning, including hierarchically organized scaffolds and multicell-polymer structures.

The purpose of this Special Issue is to highlight the recent achievements in the use of polymers as cell scaffolds on a broad scale, not only limited to the use of polymers as cell-culture scaffolds, but also including polymer-based approaches for controlling interfacial interactions of cells in vitro.

Prof. Dr. Insung S. Choi
Prof. Dr. João F. Mano
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Polymers is an international peer-reviewed open access monthly 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 1400 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

  • polymer scaffolds
  • biomaterials
  • cell-surface engineering
  • biodegradable polymers
  • hydrogels
  • biomimetic substrates

Related Special Issue

Published Papers (24 papers)

View options order results:
result details:
Displaying articles 1-24
Export citation of selected articles as:

Editorial

Jump to: Research, Review

Open AccessEditorial Advanced Control over Cell-Material Interfaces
Polymers 2017, 9(12), 704; doi:10.3390/polym9120704
Received: 13 November 2017 / Revised: 30 November 2017 / Accepted: 30 November 2017 / Published: 12 December 2017
PDF Full-text (134 KB) | HTML Full-text | XML Full-text
Abstract
Cells in vivo sense and respond to signals from their environment (e.g., other cells and extracellular matrices) for their orchestrated behaviour and function.[...] Full article

Research

Jump to: Editorial, Review

Open AccessArticle Incorporation of Calcium Containing Mesoporous (MCM-41-Type) Particles in Electrospun PCL Fibers by Using Benign Solvents
Polymers 2017, 9(10), 487; doi:10.3390/polym9100487
Received: 10 July 2017 / Revised: 19 September 2017 / Accepted: 26 September 2017 / Published: 4 October 2017
PDF Full-text (5647 KB) | HTML Full-text | XML Full-text
Abstract
The electrospinning technique is a versatile method for the production of fibrous scaffolds able to resemble the morphology of the native extra cellular matrix. In the present paper, electrospinning is used to fabricate novel SiO2 particles (type MCM-41) containing poly(epsilon-caprolactone) (PCL) fibers. The
[...] Read more.
The electrospinning technique is a versatile method for the production of fibrous scaffolds able to resemble the morphology of the native extra cellular matrix. In the present paper, electrospinning is used to fabricate novel SiO2 particles (type MCM-41) containing poly(epsilon-caprolactone) (PCL) fibers. The main aims of the present work are both the optimization of the particle synthesis and the fabrication of composite fibers, obtained using benign solvents, suitable as drug delivery systems and scaffolds for soft tissue engineering applications. The optimized synthesis and characterization of calcium-containing MCM-41 particles are reported. Homogeneous bead-free composite electrospun mats were obtained by using acetic acid and formic acid as solvents; neat PCL electrospun mats were used as control. Initially, an optimization of the electrospinning environmental parameters, like relative humidity, was performed. The obtained composite nanofibers were characterized from the morphological, chemical and mechanical points of view, the acellular bioactivity of the composite nanofibers was also investigated. Positive results were obtained in terms of mesoporous particle incorporation in the fibers and no significant differences in terms of average fiber diameter were detected between the neat and composite electrospun fibers. Even if the Ca-containing MCM-41 particles are bioactive, this property is not preserved in the composite fibers. In fact, during the bioactivity assessment, the particles were released confirming the potential application of the composite fibers as a drug delivery system. Preliminary in vitro tests with bone marrow stromal cells were performed to investigate cell adhesion on the fabricated composite mats, the positive obtained results confirmed the suitability of the composite fibers as scaffolds for soft tissue engineering. Full article
Figures

Open AccessArticle Osteogenesis of Adipose-Derived and Bone Marrow Stem Cells with Polycaprolactone/Tricalcium Phosphate and Three-Dimensional Printing Technology in a Dog Model of Maxillary Bone Defects
Polymers 2017, 9(9), 450; doi:10.3390/polym9090450
Received: 25 July 2017 / Revised: 12 September 2017 / Accepted: 12 September 2017 / Published: 15 September 2017
PDF Full-text (11811 KB) | HTML Full-text | XML Full-text
Abstract
Bone graft material should possess sufficient porosity and permeability to allow integration with native tissue and vascular invasion, and must satisfy oxygen and nutrient transport demands. In this study, we have examined the use of three-dimensional (3D)-printed polycaprolactone/tricalcium phosphate (PCL/TCP) composite material in
[...] Read more.
Bone graft material should possess sufficient porosity and permeability to allow integration with native tissue and vascular invasion, and must satisfy oxygen and nutrient transport demands. In this study, we have examined the use of three-dimensional (3D)-printed polycaprolactone/tricalcium phosphate (PCL/TCP) composite material in bone grafting, to estimate the scope of its potential application in bone surgery. Adipose-derived stem cells (ADSCs) and bone marrow stem cells (BMSCs) are known to enhance osteointegration. We hypothesized that a patient-specific 3D-printed solid scaffold could help preserve seeded ADSCs and BMSCs and enhance osteointegration. Diffuse osteogenic tissue formation was observed by micro-computed tomography with both stem cell types, and the ADSC group displayed similar osteogenesis compared to the BMSC group. In histological assessment, the scaffold pores showed abundant ossification in both groups. Reverse transcription polymerase chain reaction (RT-PCR) showed that the BMSC group had higher expression of genes associated with ossification, and this was confirmed by Western blot analysis. The ADSC- and BMSC-seeded 3D-printed PCL/TCP scaffolds displayed promising enhancement of osteogenesis in a dog model of maxillary bone defects. Full article
Figures

Open AccessCommunication Multilayered Films Produced by Layer-by-Layer Assembly of Chitosan and Alginate as a Potential Platform for the Formation of Human Adipose-Derived Stem Cell aggregates
Polymers 2017, 9(9), 440; doi:10.3390/polym9090440
Received: 10 August 2017 / Revised: 5 September 2017 / Accepted: 6 September 2017 / Published: 13 September 2017
PDF Full-text (3097 KB) | HTML Full-text | XML Full-text
Abstract
The construction of multilayered films with tunable properties could offer new routes to produce biomaterials as a platform for 3D cell cultivation. In this study, multilayered films produced with five bilayers of chitosan and alginate (CHT/ALG) were built using water-soluble modified mesyl and
[...] Read more.
The construction of multilayered films with tunable properties could offer new routes to produce biomaterials as a platform for 3D cell cultivation. In this study, multilayered films produced with five bilayers of chitosan and alginate (CHT/ALG) were built using water-soluble modified mesyl and tosyl–CHT via layer-by-layer (LbL) self-assembly. NMR results demonstrated the presences of mesyl (2.83 ppm) and tosyl groups (2.39, 7.37 and 7.70 ppm) in the chemical structure of modified chitosans. The buildup of multilayered films was monitored by quartz-crystal-microbalance (QCM-D) and film thickness was estimated using the Voigt-based viscoelastic model. QCM-D results demonstrated that CHT/ALG films constructed using mesyl or tosyl modifications (mCHT/ALG) were significantly thinner in comparison to the CHT/ALG films constructed with unmodified chitosan (p < 0.05). Adhesion analysis demonstrated that human adipose stem cells (hASCs) did not adhere to the mCHT/ALG multilayered films and formed aggregates with sizes between ca. 100–200 µm. In vitro studies on cell metabolic activity and live/dead staining suggested that mCHT/ALG multilayered films are nontoxic toward hACSs. Multilayered films produced via LbL assembly of ALG and off-the-shelf, water-soluble modified chitosans could be used as a scaffold for the 3D aggregates formation of hASCs in vitro. Full article
Figures

Open AccessArticle In Vitro and in Vivo Study of Poly(Lactic–co–Glycolic) (PLGA) Membranes Treated with Oxygen Plasma and Coated with Nanostructured Hydroxyapatite Ultrathin Films for Guided Bone Regeneration Processes
Polymers 2017, 9(9), 410; doi:10.3390/polym9090410
Received: 23 June 2017 / Revised: 30 August 2017 / Accepted: 30 August 2017 / Published: 2 September 2017
PDF Full-text (6198 KB) | HTML Full-text | XML Full-text
Abstract
The novelty of this study is the addition of an ultrathin layer of nanostructured hydroxyapatite (HA) on oxygen plasma modified poly(lactic–co–glycolic) (PLGA) membranes (PO2) in order to evaluate the efficiency of this novel material in bone regeneration. Methods: Two
[...] Read more.
The novelty of this study is the addition of an ultrathin layer of nanostructured hydroxyapatite (HA) on oxygen plasma modified poly(lactic–co–glycolic) (PLGA) membranes (PO2) in order to evaluate the efficiency of this novel material in bone regeneration. Methods: Two groups of regenerative membranes were prepared: PLGA (control) and PLGA/PO2/HA (experimental). These membranes were subjected to cell cultures and then used to cover bone defects prepared on the skulls of eight experimental rabbits. Results: Cell morphology and adhesion of the osteoblasts to the membranes showed that the osteoblasts bound to PLGA were smaller and with a lower number of adhered cells than the osteoblasts bound to the PLGA/PO2/HA membrane (p < 0.05). The PLGA/PO2/HA membrane had a higher percentage of viable cells bound than the control membrane (p < 0.05). Both micro-CT and histological evaluation confirmed that PLGA/PO2/HA membranes enhance bone regeneration. A statistically significant difference in the percentage of osteoid area in relation to the total area between both groups was found. Conclusions: The incorporation of nanometric layers of nanostructured HA into PLGA membranes modified with PO2 might be considered for the regeneration of bone defects. PLGA/PO2/HA membranes promote higher osteosynthetic activity, new bone formation, and mineralisation than the PLGA control group. Full article
Figures

Open AccessArticle Human Mesenchymal Stem Cells Differentiation Regulated by Hydroxyapatite Content within Chitosan-Based Scaffolds under Perfusion Conditions
Polymers 2017, 9(9), 387; doi:10.3390/polym9090387
Received: 21 July 2017 / Revised: 18 August 2017 / Accepted: 21 August 2017 / Published: 23 August 2017
PDF Full-text (4900 KB) | HTML Full-text | XML Full-text
Abstract
The extensive need for hard tissue substituent greatly motivates development of suitable allogeneic grafts for therapeutic recreation. Different calcium phosphate phases have been accepted as scaffold’s components with positive influence on osteoinduction and differentiation of human mesenchymal stem cells, in terms of their
[...] Read more.
The extensive need for hard tissue substituent greatly motivates development of suitable allogeneic grafts for therapeutic recreation. Different calcium phosphate phases have been accepted as scaffold’s components with positive influence on osteoinduction and differentiation of human mesenchymal stem cells, in terms of their higher fraction within the graft. Nevertheless, the creation of unlimited nutrients diffusion through newly formed grafts is of great importance. The media flow accomplished by perfusion forces can provide physicochemical, and also, biomechanical stimuli for three-dimensional bone-construct growth. In the present study, the influence of a different scaffold’s composition on the human mesenchymal stem cells (hMSCs) differentiation performed in a U-CUP bioreactor under perfusion conditioning was investigated. The histological and immunohistochemical analysis of cultured bony tissues, and the evaluation of osteogenic genes’ expression indicate that the lower fraction of in situ formed hydroxyapatite in the range of 10–30% within chitosan scaffold could be preferable for bone-construct development. Full article
Figures

Open AccessArticle Mechanical Properties of Composite Hydrogels of Alginate and Cellulose Nanofibrils
Polymers 2017, 9(8), 378; doi:10.3390/polym9080378
Received: 27 June 2017 / Revised: 10 August 2017 / Accepted: 17 August 2017 / Published: 19 August 2017
PDF Full-text (9988 KB) | HTML Full-text | XML Full-text
Abstract
Alginate and cellulose nanofibrils (CNF) are attractive materials for tissue engineering and regenerative medicine. CNF gels are generally weaker and more brittle than alginate gels, while alginate gels are elastic and have high rupture strength. Alginate properties depend on their guluronan and mannuronan
[...] Read more.
Alginate and cellulose nanofibrils (CNF) are attractive materials for tissue engineering and regenerative medicine. CNF gels are generally weaker and more brittle than alginate gels, while alginate gels are elastic and have high rupture strength. Alginate properties depend on their guluronan and mannuronan content and their sequence pattern and molecular weight. Likewise, CNF exists in various qualities with properties depending on, e.g., morphology and charge density. In this study combinations of three types of alginate with different composition and two types of CNF with different charge and degree of fibrillation have been studied. Assessments of the composite gels revealed that attractive properties like high rupture strength, high compressibility, high gel rigidity at small deformations (Young’s modulus), and low syneresis was obtained compared to the pure gels. The effects varied with relative amounts of CNF and alginate, alginate type, and CNF quality. The largest effects were obtained by combining oxidized CNF with the alginates. Hence, by combining the two biopolymers in composite gels, it is possible to tune the rupture strength, Young’s modulus, syneresis, as well as stability in physiological saline solution, which are all important properties for the use as scaffolds in tissue engineering. Full article
Figures

Open AccessArticle Effect of Catechol Content in Catechol-Conjugated Dextrans on Antiplatelet Performance
Polymers 2017, 9(8), 376; doi:10.3390/polym9080376
Received: 26 June 2017 / Revised: 17 August 2017 / Accepted: 17 August 2017 / Published: 19 August 2017
PDF Full-text (1820 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The surface coating of solid substrates using dextrans has gained a great deal of attention, because dextran-coated surfaces show excellent anti-fouling property as well as biocompatibility behavior. Much effort has been made to develop efficient methods for grafting dextrans on solid surfaces. This
[...] Read more.
The surface coating of solid substrates using dextrans has gained a great deal of attention, because dextran-coated surfaces show excellent anti-fouling property as well as biocompatibility behavior. Much effort has been made to develop efficient methods for grafting dextrans on solid surfaces. This led to the development of catechol-conjugated dextrans (Dex-C) which can adhere to a number of solid surfaces, inspired by the underwater adhesion behavior of marine mussels. The present study is a systematic investigation of the characteristics of surface coatings developed with Dex-C. Various Dex-C with different catechol contents were synthesized and used as a surface coating material. The effect of catechol content on surface coating and antiplatelet performance was investigated. Full article
Figures

Open AccessArticle Enhanced Cartilaginous Tissue Formation with a Cell Aggregate-Fibrin-Polymer Scaffold Complex
Polymers 2017, 9(8), 348; doi:10.3390/polym9080348
Received: 28 June 2017 / Revised: 3 August 2017 / Accepted: 3 August 2017 / Published: 8 August 2017
Cited by 1 | PDF Full-text (14924 KB) | HTML Full-text | XML Full-text
Abstract
Cell density is one of the factors required in the preparation of engineered cartilage from mesenchymal stem cells (MSCs). Additionally, it is well known for having a significant role in chemical and physical stimulations when stem cells undergo chondrogenic differentiation. Here, we developed
[...] Read more.
Cell density is one of the factors required in the preparation of engineered cartilage from mesenchymal stem cells (MSCs). Additionally, it is well known for having a significant role in chemical and physical stimulations when stem cells undergo chondrogenic differentiation. Here, we developed an engineered cartilage with a cell aggregate-hydrogel-polymer scaffold complex capable of inducing the effective regeneration of cartilage tissue similar to natural cartilage while retaining a high mechanical strength, flexibility, and morphology. Cell aggregates were generated by the hanging drop method with rabbit bone marrow stromal cells (BMSCs), and poly (lactide-co-caprolactone) (PLCL) scaffolds were fabricated with 78.3 ± 5.3% porosity and a 300–500 μm pore size with a gel-pressing method. We prepared the cell aggregate-fibrin-poly (lactide-co-caprolactone) (PLCL) scaffold complex, in which the cell aggregates were evenly dispersed in the fibrin, and they were immobilized onto the surface of the polymer scaffold while filling up the pores. To examine the chondrogenic differentiation of seeded BMSCs and the formation of chondral extracellular matrix onto the complexes, they were cultured in vitro or subcutaneously implanted into nude mice for up to eight weeks. The results of the in vitro and in vivo studies revealed that the accumulation of the chondral extracellular matrices was increased on the cell aggregate-fibrin-PLCL scaffold complexes (CAPs) compared to the single cell-fibrin-PLCL scaffold complexes (SCPs). Additionally, we examined whether the mature and well-developed cartilaginous tissues and lacunae structures typical of mature cartilage were evenly distributed in the CAPs. Consequently, the cell aggregates in the hybrid scaffolds of fibrin gels and elastic PLCL scaffolds can induce themselves to differentiate into chondrocytes, maintain their phenotypes, enhance glycosaminoglycan (GAG) production, and improve the quality of cartilaginous tissue formed in vitro and in vivo. Full article
Figures

Open AccessArticle Electrospinning PCL Scaffolds Manufacture for Three-Dimensional Breast Cancer Cell Culture
Polymers 2017, 9(8), 328; doi:10.3390/polym9080328
Received: 27 June 2017 / Revised: 23 July 2017 / Accepted: 27 July 2017 / Published: 1 August 2017
PDF Full-text (9486 KB) | HTML Full-text | XML Full-text
Abstract
In vitro cell culture is traditionally performed within two-dimensional (2D) environments, providing a quick and cheap way to study cell properties in a laboratory. However, 2D systems differ from the in vivo environment and may not mimic the physiological cell behavior realistically. For
[...] Read more.
In vitro cell culture is traditionally performed within two-dimensional (2D) environments, providing a quick and cheap way to study cell properties in a laboratory. However, 2D systems differ from the in vivo environment and may not mimic the physiological cell behavior realistically. For instance, 2D culture models are thought to induce cancer stem cells (CSCs) differentiation, a rare cancer cell subpopulation responsible for tumor initiation and relapse. This fact hinders the development of therapeutic strategies for tumors with a high relapse percentage, such as triple negative breast cancer (TNBC). Thus, three-dimensional (3D) scaffolds have emerged as an attractive alternative to monolayer culture, simulating the extracellular matrix structure and maintaining the differentiation state of cells. In this work, scaffolds were fabricated through electrospinning different poly(ε-caprolactone)-acetone solutions. Poly(ε-caprolactone) (PCL) meshes were seeded with triple negative breast cancer (TNBC) cells and 15% PCL scaffolds displayed significantly (p < 0.05) higher cell proliferation and elongation than the other culture systems. Moreover, cells cultured on PCL scaffolds exhibited higher mammosphere forming capacity and aldehyde dehydrogenase activity than 2D-cultured cells, indicating a breast CSCs enrichment. These results prove the powerful capability of electrospinning technology in terms of poly(ε-caprolactone) nanofibers fabrication. In addition, this study has demonstrated that electrospun 15% PCL scaffolds are suitable tools to culture breast cancer cells in a more physiological way and to expand the niche of breast CSCs. In conclusion, three-dimensional cell culture using PCL scaffolds could be useful to study cancer stem cell behavior and may also trigger the development of new specific targets against such malignant subpopulation. Full article
Figures

Open AccessArticle Manipulating Living Cells to Construct a 3D Single-Cell Assembly without an Artificial Scaffold
Polymers 2017, 9(8), 319; doi:10.3390/polym9080319
Received: 30 June 2017 / Revised: 24 July 2017 / Accepted: 25 July 2017 / Published: 30 July 2017
PDF Full-text (2810 KB) | HTML Full-text | XML Full-text
Abstract
Artificial scaffolds such as synthetic gels or chemically-modified glass surfaces that have often been used to achieve cell adhesion are xenobiotic and may harm cells. To enhance the value of cell studies in the fields of regenerative medicine and tissue engineering, it is
[...] Read more.
Artificial scaffolds such as synthetic gels or chemically-modified glass surfaces that have often been used to achieve cell adhesion are xenobiotic and may harm cells. To enhance the value of cell studies in the fields of regenerative medicine and tissue engineering, it is becoming increasingly important to create a cell-friendly technique to promote cell–cell contact. In the present study, we developed a novel method for constructing stable cellular assemblies by using optical tweezers in a solution of a natural hydrophilic polymer, dextran. In this method, a target cell is transferred to another target cell to make cell–cell contact by optical tweezers in a culture medium containing dextran. When originally non-cohesive cells are held in contact with each other for a few minutes under laser trapping, stable cell–cell adhesion is accomplished. This method for creating cellular assemblies in the presence of a natural hydrophilic polymer may serve as a novel next-generation 3D single-cell assembly system with future applications in the growing field of regenerative medicine. Full article
Figures

Figure 1

Open AccessFeature PaperArticle In Vitro Evaluation of Essential Mechanical Properties and Cell Behaviors of a Novel Polylactic-co-Glycolic Acid (PLGA)-Based Tubular Scaffold for Small-Diameter Vascular Tissue Engineering
Polymers 2017, 9(8), 318; doi:10.3390/polym9080318
Received: 12 June 2017 / Revised: 23 July 2017 / Accepted: 27 July 2017 / Published: 30 July 2017
Cited by 1 | PDF Full-text (3501 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this paper, we investigate essential mechanical properties and cell behaviors of the scaffolds fabricated by rolling polylactic-co-glycolic acid (PLGA) electrospinning (ES) films for small-diameter vascular grafts (inner diameter < 6 mm). The newly developed strategy can be used to fabricate
[...] Read more.
In this paper, we investigate essential mechanical properties and cell behaviors of the scaffolds fabricated by rolling polylactic-co-glycolic acid (PLGA) electrospinning (ES) films for small-diameter vascular grafts (inner diameter < 6 mm). The newly developed strategy can be used to fabricate small diameter vascular grafts with or without pre-seeded cells, which are two main branches for small diameter vascular engineering. We demonstrate that the mechanical properties of our rolling-based scaffolds can be tuned flexibly by the number of layers. For cell-free scaffolds, with the increase of layer number, burst pressure and suture retention increase, elastic tensile modulus maintains unchanged statistically, but compliance and liquid leakage decrease. For cell-containing scaffolds, seeding cells will significantly decrease the liquid leakage, but there are no statistical differences for other mechanical properties; moreover, cells live and proliferate well in the scaffold after a 6-day culture. Full article
Figures

Open AccessArticle Biphasic Calcium Phosphate (BCP)-Immobilized Porous Poly (d,l-Lactic-co-Glycolic Acid) Microspheres Enhance Osteogenic Activities of Osteoblasts
Polymers 2017, 9(7), 297; doi:10.3390/polym9070297
Received: 27 June 2017 / Revised: 11 July 2017 / Accepted: 18 July 2017 / Published: 21 July 2017
PDF Full-text (4232 KB) | HTML Full-text | XML Full-text
Abstract
The purpose of this study was to evaluate the potential of porous poly (d,l-lactic-co-glycolic acid) (PLGA) microspheres (PMSs) immobilized on biphasic calcium phosphate nanoparticles (BCP NPs) (BCP-IM-PMSs) to enhance osteogenic activity. PMSs were fabricated using a fluidic device, and their surfaces
[...] Read more.
The purpose of this study was to evaluate the potential of porous poly (d,l-lactic-co-glycolic acid) (PLGA) microspheres (PMSs) immobilized on biphasic calcium phosphate nanoparticles (BCP NPs) (BCP-IM-PMSs) to enhance osteogenic activity. PMSs were fabricated using a fluidic device, and their surfaces were modified with l-lysine (aminated-PMSs), whereas the BCP NPs were modified with heparin–dopamine (Hep-DOPA) to obtain heparinized–BCP (Hep-BCP) NPs. BCP-IM-PMSs were fabricated via electrostatic interactions between the Hep-BCP NPs and aminated-PMSs. The fabricated BCP-IM-PMSs showed an interconnected pore structure. In vitro studies showed that MG-63 cells cultured on BCP-IM-PMSs had increased alkaline phosphatase activity, calcium content, and mRNA expression of osteocalcin (OCN) and osteopontin (OPN) compared with cells cultured on PMSs. These data suggest that BCP NP-immobilized PMSs have the potential to enhance osteogenic activity. Full article
Figures

Figure 1

Open AccessArticle Preparation of Pendant Group-Functionalized Diblock Copolymers with Adjustable Thermogelling Behavior
Polymers 2017, 9(6), 239; doi:10.3390/polym9060239
Received: 9 May 2017 / Revised: 18 June 2017 / Accepted: 18 June 2017 / Published: 20 June 2017
Cited by 1 | PDF Full-text (5102 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recently, several thermogelling materials have been developed for biomedical applications. In this study, we prepared methoxy polyethylene glycol (MPEG)-b-(poly(ε-caprolactone)-ran-poly(2-chloride-ε-caprolactone) (PCL-ran-PfCL)) (MP-Cl) diblock copolymers at room temperature via the ring-opening polymerization of caprolactone (CL)
[...] Read more.
Recently, several thermogelling materials have been developed for biomedical applications. In this study, we prepared methoxy polyethylene glycol (MPEG)-b-(poly(ε-caprolactone)-ran-poly(2-chloride-ε-caprolactone) (PCL-ran-PfCL)) (MP-Cl) diblock copolymers at room temperature via the ring-opening polymerization of caprolactone (CL) and 2-chloride-ε-caprolactone (fCL) monomers, using the terminal alcohol of MPEG as the initiator in the presence of HCl. MPEG-b-(poly(ε-caprolactone)-ran-poly(2-azide-ε-caprolactone) (PCL-ran-PCL-N3)) (MP-N3) was prepared by the reaction of MP-Cl with sodium azide. MPEG-b-(poly(ε-caprolactone)-ran-poly(2-amine-ε-caprolactone) (PCL-ran-PCL-NH2)) (MP-NH2) was subsequently prepared by Staudinger reaction. MP-Cl and MP-N3 showed negative zeta potentials, but MP-NH2 had a positive zeta potential. MP-Cl, MP-N3, and MP-NH2 solutions formed opaque emulsions at room temperature. The solutions exhibited a solution-to-hydrogel phase transition as a function of the temperature and were affected by variation of the chloride, azide, and the amine pendant group, as well as the amount of pendant groups present in their structure. Additionally, the phase transition of MP-Cl, MP-N3, and MP-NH2 copolymers was altered by pendant groups. The solution-to-hydrogel phase transition was adjusted by tailoring the crystallinity and hydrophobicity of the copolymers in aqueous solutions. Collectively, MP-Cl, MP-N3, and MP-NH2 with various pendant-group contents in the PCL segment showed a solution-to-hydrogel phase transition that depended on both the type of pendant groups and their content. Full article
Figures

Open AccessArticle In Vitro Biocompatibility, Radiopacity, and Physical Property Tests of Nano-Fe3O4 Incorporated Poly-l-lactide Bone Screws
Polymers 2017, 9(6), 191; doi:10.3390/polym9060191
Received: 18 April 2017 / Revised: 20 May 2017 / Accepted: 24 May 2017 / Published: 26 May 2017
PDF Full-text (4507 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to fabricate biodegradable poly-l-lactic acid (PLLA) bone screws containing iron oxide (Fe3O4) nanoparticles, which are radiopaque and 3D-printable. The PLLA composites were fabricated by loading 20%, 30%, and 40% Fe3O4
[...] Read more.
The aim of this study was to fabricate biodegradable poly-l-lactic acid (PLLA) bone screws containing iron oxide (Fe3O4) nanoparticles, which are radiopaque and 3D-printable. The PLLA composites were fabricated by loading 20%, 30%, and 40% Fe3O4 nanoparticles into the PLLA. The physical properties, including elastic modulus, thermal properties, and biocompatibility of the composites were tested. The 20% nano-Fe3O4/PLLA composite was used as the material for fabricating the 3D-printed bone screws. The mechanical performance of the nano-Fe3O4/PLLA bone screws was evaluated by anti-bending and anti-torque strength tests. The tissue response and radiopacity of the nano-Fe3O4/PLLA bone screws were assessed by histologic and CT imaging studies using an animal model. The addition of nano-Fe3O4 increased the crystallization of the PLLA composites. Furthermore, the 20% nano-Fe3O4/PLLA composite exhibited the highest thermal stability compared to the other Fe3O4 proportions. The 3D-printed bone screws using the 20% nano-Fe3O4/PLLA composite provided excellent local tissue response. In addition, the radiopacity of the 20% nano-Fe3O4/PLLA screw was significantly better compared with the neat PLLA screw. Full article
Figures

Figure 1

Open AccessArticle Osteochondral Regeneration Induced by TGF-β Loaded Photo Cross-Linked Hyaluronic Acid Hydrogel Infiltrated in Fused Deposition-Manufactured Composite Scaffold of Hydroxyapatite and Poly (Ethylene Glycol)-Block-Poly(ε-Caprolactone)
Polymers 2017, 9(5), 182; doi:10.3390/polym9050182
Received: 6 March 2017 / Revised: 11 May 2017 / Accepted: 14 May 2017 / Published: 20 May 2017
Cited by 1 | PDF Full-text (3268 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to report the fabrication of porous scaffolds with pre-designed internal pores using a fused deposition modeling (FDM) method. Polycaprolactone (PCL) is a suitable material for the FDM method due to the fact it can be melted and
[...] Read more.
The aim of this study was to report the fabrication of porous scaffolds with pre-designed internal pores using a fused deposition modeling (FDM) method. Polycaprolactone (PCL) is a suitable material for the FDM method due to the fact it can be melted and has adequate flexural modulus and strength to be formed into a filament. In our study, the filaments of methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) having terminal groups of carboxylic acid were deposited layer by layer. Raw materials having a weight ratio of hydroxyapatite (HAp) to polymer of 1:2 was used for FDM. To promote cell adhesion, amino groups of the Arg-Gly-Asp(RGD) peptide were condensed with the carboxylic groups on the surface of the fabricated scaffold. Then the scaffold was infiltrated with hydrogel of glycidyl methacrylate hyaluronic acid loading with 10 ng/mL of TGF-β1 and photo cross-linked on the top of the scaffolds. Serious tests of mechanical and biological properties were performed in vitro. HAp was found to significantly increase the compressive strength of the porous scaffolds. Among three orientations of the filaments, the lay down pattern 0°/90° scaffolds exhibited the highest compressive strength. Fluorescent staining of the cytoskeleton found that the osteoblast-like cells and stem cells well spread on RGD-modified PEG-PCL film indicating a favorable surface for the proliferation of cells. An in vivo test was performed on rabbit knee. The histological sections indicated that the bone and cartilage defects produced in the knees were fully healed 12 weeks after the implantation of the TGF-β1 loaded hydrogel and scaffolds, and regenerated cartilage was hyaline cartilage as indicated by alcian blue and periodic acid-schiff double staining. Full article
Figures

Figure 1

Open AccessArticle Calcium Silicate Improved Bioactivity and Mechanical Properties of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Scaffolds
Polymers 2017, 9(5), 175; doi:10.3390/polym9050175
Received: 2 April 2017 / Revised: 12 May 2017 / Accepted: 12 May 2017 / Published: 14 May 2017
PDF Full-text (30659 KB) | HTML Full-text | XML Full-text
Abstract
The poor bioactivity and mechanical properties have restricted its biomedical application, although poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) had good biocompatibility and biodegradability. In this study, calcium silicate (CS) was incorporated into PHBV for improving its bioactivity and mechanical properties, and the porous PHBV/CS composite scaffolds were
[...] Read more.
The poor bioactivity and mechanical properties have restricted its biomedical application, although poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) had good biocompatibility and biodegradability. In this study, calcium silicate (CS) was incorporated into PHBV for improving its bioactivity and mechanical properties, and the porous PHBV/CS composite scaffolds were fabricated via selective laser sintering (SLS). Simulated body fluid (SBF) immersion tests indicated the composite scaffolds had good apatite-forming ability, which could be mainly attributed to the electrostatic attraction of negatively charged silanol groups derived from CS degradation to positively charged calcium ions in SBF. Moreover, the compressive properties of the composite scaffolds increased at first, and then decreased with increasing the CS content, which was ascribed to the fact that CS of a proper content could homogeneously disperse in PHBV matrix, while excessive CS would form continuous phase. The compressive strength and modulus of composite scaffolds with optimal CS content of 10 wt % were 3.55 MPa and 36.54 MPa, respectively, which were increased by 41.43% and 28.61%, respectively, as compared with PHBV scaffolds. Additionally, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated MG63 cells had a higher proliferation rate on PHBV/CS composite scaffolds than that on PHBV. Alkaline phosphatase (ALP) staining assay demonstrated the incorporation of CS significantly promoted osteogenic differentiation of MG63 cells on the scaffolds. These results suggest that the PHBV/CS composite scaffolds have the potential in serving as a substitute in bone tissue engineering. Full article
Figures

Open AccessArticle Artificial Spores: Immunoprotective Nanocoating of Red Blood Cells with Supramolecular Ferric Ion-Tannic Acid Complex
Polymers 2017, 9(4), 140; doi:10.3390/polym9040140
Received: 20 March 2017 / Revised: 12 April 2017 / Accepted: 12 April 2017 / Published: 13 April 2017
Cited by 1 | PDF Full-text (1916 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The blood-type-mismatch problem, in addition to shortage of blood donation, in blood transfusion has prompted the researchers to develop universal blood that does not require blood typing. In this work, the “cell-in-shell” (i.e., artificial spore) approach is utilized to shield the immune-provoking epitopes
[...] Read more.
The blood-type-mismatch problem, in addition to shortage of blood donation, in blood transfusion has prompted the researchers to develop universal blood that does not require blood typing. In this work, the “cell-in-shell” (i.e., artificial spore) approach is utilized to shield the immune-provoking epitopes on the surface of red blood cells (RBCs). Individual RBCs are successfully coated with supramolecular metal-organic coordination complex of ferric ion (FeIII) and tannic acid (TA). The use of isotonic saline (0.85% NaCl) is found to be critical in the formation of stable, reasonably thick (20 nm) shells on RBCs without any aggregation and hemolysis. The formed “RBC-in-shell” structures maintain their original shapes, and effectively attenuate the antibody-mediated agglutination. Moreover, the oxygen-carrying capability of RBCs is not deteriorated after shell formation. This work suggests a simple but fast method for generating immune-camouflaged RBCs, which would contribute to the development of universal blood. Full article
Figures

Open AccessArticle Cell Proliferation on Polyethylene Terephthalate Treated in Plasma Created in SO2/O2 Mixtures
Polymers 2017, 9(3), 82; doi:10.3390/polym9030082
Received: 3 January 2017 / Revised: 20 February 2017 / Accepted: 22 February 2017 / Published: 25 February 2017
PDF Full-text (10976 KB) | HTML Full-text | XML Full-text
Abstract
Samples of polymer polyethylene terephthalate were exposed to a weakly ionized gaseous plasma to modify the polymer surface properties for better cell cultivation. The gases used for treatment were sulfur dioxide and oxygen of various partial pressures. Plasma was created by an electrodeless
[...] Read more.
Samples of polymer polyethylene terephthalate were exposed to a weakly ionized gaseous plasma to modify the polymer surface properties for better cell cultivation. The gases used for treatment were sulfur dioxide and oxygen of various partial pressures. Plasma was created by an electrodeless radio frequency discharge at a total pressure of 60 Pa. X-ray photoelectron spectroscopy showed weak functionalization of the samples’ surfaces with the sulfur, with a concentration around 2.5 at %, whereas the oxygen concentration remained at the level of untreated samples, except when the gas mixture with oxygen concentration above 90% was used. Atomic force microscopy revealed highly altered morphology of plasma-treated samples; however, at high oxygen partial pressures this morphology vanished. The samples were then incubated with human umbilical vein endothelial cells. Biological tests to determine endothelialization and possible toxicity of the plasma-treated polyethylene terephthalate samples were performed. Cell metabolic activity (MTT) and in vitro toxic effects of unknown compounds (TOX) were assayed to determine the biocompatibility of the treated substrates. The biocompatibility demonstrated a well-pronounced maximum versus gas composition which correlated well with development of the surface morphology. Full article
Figures

Open AccessArticle A Biodegradable Microneedle Cuff for Comparison of Drug Effects through Perivascular Delivery to Balloon-Injured Arteries
Polymers 2017, 9(2), 56; doi:10.3390/polym9020056
Received: 5 January 2017 / Revised: 25 January 2017 / Accepted: 3 February 2017 / Published: 8 February 2017
Cited by 1 | PDF Full-text (9234 KB) | HTML Full-text | XML Full-text
Abstract
Restenosis at a vascular anastomosis site is a major cause of graft failure and is difficult to prevent by conventional treatment. Perivascular drug delivery has advantages as drugs can be diffused to tunica media and subintima while minimizing the direct effect on endothelium.
[...] Read more.
Restenosis at a vascular anastomosis site is a major cause of graft failure and is difficult to prevent by conventional treatment. Perivascular drug delivery has advantages as drugs can be diffused to tunica media and subintima while minimizing the direct effect on endothelium. This in vivo study investigated the comparative effectiveness of paclitaxel, sirolimus, and sunitinib using a perivascular biodegradable microneedle cuff. A total of 31 New Zealand white rabbits were used. Rhodamine was used to visualize drug distribution (n = 3). Sirolimus- (n = 7), sunitinib- (n = 7), and paclitaxel-loaded (n = 7) microneedle cuffs were placed at balloon-injured abdominal aortae and compared to drug-free cuffs (n = 7). Basic histological structures were not affected by microneedle devices, and vascular wall thickness of the device-only group was similar to that of normal artery. Quantitative analysis revealed significantly decreased neointima formation in all drug-treated groups (p < 0.001). However, the tunica media layer of the paclitaxel-treated group was significantly thinner than that of other groups and also showed the highest apoptotic ratio (p < 0.001). Proliferating cell nuclear antigen (PCNA)-positive cells were significantly reduced in all drug-treated groups. Sirolimus or sunitinib appeared to be more appropriate for microneedle devices capable of slow drug release because vascular wall thickness was minimally affected. Full article
Figures

Figure 1

Open AccessArticle Microsphere-Based Hierarchically Juxtapositioned Biphasic Scaffolds Prepared from Poly(Lactic-co-Glycolic Acid) and Nanohydroxyapatite for Osteochondral Tissue Engineering
Polymers 2016, 8(12), 429; doi:10.3390/polym8120429
Received: 12 October 2016 / Revised: 18 November 2016 / Accepted: 5 December 2016 / Published: 10 December 2016
Cited by 2 | PDF Full-text (32992 KB) | HTML Full-text | XML Full-text
Abstract
This study aims to prepare biphasic osteochondral scaffolds based on seamless joining of sintered polymer and polymer/ceramic microspheres for co-culture of chondrocytes and bone marrow stem cells (BMSCs). Poly(lactide-co-glycolide) (PLGA) microspheres and 10% nanohydroxyapatite (nHAP)-incorporated PLGA (PGA/nHAP) microspheres were prepared through
[...] Read more.
This study aims to prepare biphasic osteochondral scaffolds based on seamless joining of sintered polymer and polymer/ceramic microspheres for co-culture of chondrocytes and bone marrow stem cells (BMSCs). Poly(lactide-co-glycolide) (PLGA) microspheres and 10% nanohydroxyapatite (nHAP)-incorporated PLGA (PGA/nHAP) microspheres were prepared through the oil-in-water precipitation method. Virgin (V) and composite (C) scaffolds were prepared from 250–500 µm PLGA and PLGA/nHAP microspheres, respectively, while osteochondral (OC) scaffolds were fabricated through the combination of V and C scaffolds. Physico-chemical properties of scaffolds were characterized through microscopic-spectroscopic evaluations. The effect of nHAP in scaffolds was investigated through thermogravimetric analysis and mechanical testing, while surface hydrophobicity was tested through contact angle measurements. Rabbit chondrocytes and BMSCs were used for cell culture, and cell morphology and proliferation were determined from SEM and DNA assays. Alizarin red and Alcian blue stains were used to identify the in vitro bone and cartilage tissue-specific regeneration, while cetylpyridinium chloride was used to quantitatively estimate calcium in mineralized bone. For co-culture in OC scaffolds, BMSCs were first seeded in the bone part of the scaffold and cultured in osteogenic medium, followed by seeding chondrocytes in the cartilage part, and cultured in chondrocyte medium. High cell viability was confirmed from the Live/Dead assays. Actin cytoskeleton organization obtained by DAPI-phalloidin staining revealed proper organization of chondrocytes and BMSCs in OC scaffolds. Immunofluorescent staining of bone (type I collagen and osteocalcin (OCN)) and cartilage marker proteins (type II collagen (COL II)) confirmed cellular behavior of osteoblasts and chondrocytes in vitro. Using an ectopic osteochondral defect model by subcutaneous implantation of co-cultured OC scaffolds in nude mice confirmed cell proliferation and tissue development from gross view and SEM observation. IF staining of OCN and COL II in the bone and cartilage parts of OC scaffolds and tissue-specific histological analysis exhibited a time-dependent tissue re-modeling and confirmed the potential application of the biphasic scaffold in osteochondral tissue engineering. Full article
Figures

Review

Jump to: Editorial, Research

Open AccessReview Hydrogels for Cartilage Regeneration, from Polysaccharides to Hybrids
Polymers 2017, 9(12), 671; doi:10.3390/polym9120671
Received: 14 October 2017 / Revised: 24 November 2017 / Accepted: 29 November 2017 / Published: 4 December 2017
PDF Full-text (3899 KB) | HTML Full-text | XML Full-text
Abstract
The aims of this paper are: (1) to review the current state of the art in the field of cartilage substitution and regeneration; (2) to examine the patented biomaterials being used in preclinical and clinical stages; (3) to explore the potential of polymeric
[...] Read more.
The aims of this paper are: (1) to review the current state of the art in the field of cartilage substitution and regeneration; (2) to examine the patented biomaterials being used in preclinical and clinical stages; (3) to explore the potential of polymeric hydrogels for these applications and the reasons that hinder their clinical success. The studies about hydrogels used as potential biomaterials selected for this review are divided into the two major trends in tissue engineering: (1) the use of cell-free biomaterials; and (2) the use of cell seeded biomaterials. Preparation techniques and resulting hydrogel properties are also reviewed. More recent proposals, based on the combination of different polymers and the hybridization process to improve the properties of these materials, are also reviewed. The combination of elements such as scaffolds (cellular solids), matrices (hydrogel-based), growth factors and mechanical stimuli is needed to optimize properties of the required materials in order to facilitate tissue formation, cartilage regeneration and final clinical application. Polymer combinations and hybrids are the most promising materials for this application. Hybrid scaffolds may maximize cell growth and local tissue integration by forming cartilage-like tissue with biomimetic features. Full article
Figures

Open AccessReview Gelatin-Based Hydrogels for Organ 3D Bioprinting
Polymers 2017, 9(9), 401; doi:10.3390/polym9090401
Received: 30 June 2017 / Revised: 8 August 2017 / Accepted: 8 August 2017 / Published: 30 August 2017
PDF Full-text (6773 KB) | HTML Full-text | XML Full-text
Abstract
Three-dimensional (3D) bioprinting is a family of enabling technologies that can be used to manufacture human organs with predefined hierarchical structures, material constituents and physiological functions. The main objective of these technologies is to produce high-throughput and/or customized organ substitutes (or bioartificial organs)
[...] Read more.
Three-dimensional (3D) bioprinting is a family of enabling technologies that can be used to manufacture human organs with predefined hierarchical structures, material constituents and physiological functions. The main objective of these technologies is to produce high-throughput and/or customized organ substitutes (or bioartificial organs) with heterogeneous cell types or stem cells along with other biomaterials that are able to repair, replace or restore the defect/failure counterparts. Gelatin-based hydrogels, such as gelatin/fibrinogen, gelatin/hyaluronan and gelatin/alginate/fibrinogen, have unique features in organ 3D bioprinting technologies. This article is an overview of the intrinsic/extrinsic properties of the gelatin-based hydrogels in organ 3D bioprinting areas with advanced technologies, theories and principles. The state of the art of the physical/chemical crosslinking methods of the gelatin-based hydrogels being used to overcome the weak mechanical properties is highlighted. A multicellular model made from adipose-derived stem cell proliferation and differentiation in the predefined 3D constructs is emphasized. Multi-nozzle extrusion-based organ 3D bioprinting technologies have the distinguished potential to eventually manufacture implantable bioartificial organs for purposes such as customized organ restoration, high-throughput drug screening and metabolic syndrome model establishment. Full article
Figures

Open AccessReview Characterization of Cell Scaffolds by Atomic Force Microscopy
Polymers 2017, 9(8), 383; doi:10.3390/polym9080383
Received: 30 July 2017 / Revised: 13 August 2017 / Accepted: 16 August 2017 / Published: 21 August 2017
PDF Full-text (1581 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This review reports on the use of the atomic force microscopy (AFM) in the investigation of cell scaffolds in recent years. It is shown how the technique is able to deliver information about the scaffold surface properties (e.g., topography), as well as about
[...] Read more.
This review reports on the use of the atomic force microscopy (AFM) in the investigation of cell scaffolds in recent years. It is shown how the technique is able to deliver information about the scaffold surface properties (e.g., topography), as well as about its mechanical behavior (Young’s modulus, viscosity, and adhesion). In addition, this short review also points out the utilization of the atomic force microscope technique beyond its usual employment in order to investigate another type of basic questions related to materials physics, chemistry, and biology. The final section discusses in detail the novel uses that those alternative measuring modes can bring to this field in the future. Full article
Figures

Back to Top