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Special Issue "Biomaterials for Tissue Engineering"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 October 2015).

Special Issue Editor

Guest Editor
Prof. Dr. Mohamed N. Rahaman

Department of Materials Science and Engineering, Missouri University of Science and Technology; Department of Bioengineering, University of Illinois at Chicago, USA
Website | E-Mail
Interests: bioceramics, bone regeneration, calcium phosphate, drug delivery matrices, biomimetic ceramics, tissue engineering, biological interactions of calcium phosphates, and osteoinduction

Special Issue Information

Dear Colleagues,

The field of tissue engineering is advancing rapidly and many of these advances would not be possible without the innovative design and development of biomaterials. The intent of this Special Issue is to cover recent advances and emerging developments in the design and development of biomaterials for engineering a wide range of tissues and organs. The Special Issue will consider the main types of biomaterials, synthetic and natural, that are being investigated for tissue engineering applications, including biodegradable polymers, hydrogels, polypeptides, inorganic materials such as bioactive ceramics and glasses, and composites, as well as technologies for forming these biomaterials into tissue engineering constructs with nanofibrous, microfibrous and macroporous three-dimensional architectures. Biomaterials for stem cell-based therapies and for growth factor and drug delivery are also of interest. The use of biomaterials in engineered regeneration of specific tissues and organs such as bone, cartilage, tendons and ligaments, skin, soft tissue wounds, cardiac muscle, vascular tissues and neural tissues, as well as composite tissue structures such as joints and periodontal ligaments, and organs such as kidney, liver and pancreas will be covered. Issues in further advancing tissue-engineered products towards clinical applications in the restoration of diseased or damaged tissues and organs will be addressed.

Mohamed N. Rahaman
Guest Editor

Manuscript Submission Information

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Keywords

  • biomaterials
  • tissue engineering
  • regenerative medicine
  • scaffolds
  • stem cells
  • growth factors
  • tissues and organs

Related Special Issue

Published Papers (27 papers)

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Open AccessArticle
Poly-ε-caprolactone Coated and Functionalized Porous Titanium and Magnesium Implants for Enhancing Angiogenesis in Critically Sized Bone Defects
Int. J. Mol. Sci. 2016, 17(1), 1; https://doi.org/10.3390/ijms17010001
Received: 28 October 2015 / Revised: 10 December 2015 / Accepted: 14 December 2015 / Published: 22 December 2015
Cited by 6 | PDF Full-text (8826 KB) | HTML Full-text | XML Full-text
Abstract
For healing of critically sized bone defects, biocompatible and angiogenesis supporting implants are favorable. Murine osteoblasts showed equal proliferation behavior on the polymers poly-ε-caprolactone (PCL) and poly-(3-hydroxybutyrate)/poly-(4-hydroxybutyrate) (P(3HB)/P(4HB)). As vitality was significantly better for PCL, it was chosen as a suitable coating material [...] Read more.
For healing of critically sized bone defects, biocompatible and angiogenesis supporting implants are favorable. Murine osteoblasts showed equal proliferation behavior on the polymers poly-ε-caprolactone (PCL) and poly-(3-hydroxybutyrate)/poly-(4-hydroxybutyrate) (P(3HB)/P(4HB)). As vitality was significantly better for PCL, it was chosen as a suitable coating material for further experiments. Titanium implants with 600 µm pore size were evaluated and found to be a good implant material for bone, as primary osteoblasts showed a vitality and proliferation onto the implants comparable to well bottom (WB). Pure porous titanium implants and PCL coated porous titanium implants were compared using Live Cell Imaging (LCI) with Green fluorescent protein (GFP)-osteoblasts. Cell count and cell covered area did not differ between the implants after seven days. To improve ingrowth of blood vessels into porous implants, proangiogenic factors like Vascular Endothelial Growth Factor (VEGF) and High Mobility Group Box 1 (HMGB1) were incorporated into PCL coated, porous titanium and magnesium implants. An angiogenesis assay was performed to establish an in vitro method for evaluating the impact of metallic implants on angiogenesis to reduce and refine animal experiments in future. Incorporated concentrations of proangiogenic factors were probably too low, as they did not lead to any effect. Magnesium implants did not yield evaluable results, as they led to pH increase and subsequent cell death. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Effects of PMMA and Cross-Linked Dextran Filler for Soft Tissue Augmentation in Rats
Int. J. Mol. Sci. 2015, 16(12), 28523-28533; https://doi.org/10.3390/ijms161226112
Received: 31 July 2015 / Revised: 27 October 2015 / Accepted: 20 November 2015 / Published: 1 December 2015
Cited by 1 | PDF Full-text (3363 KB) | HTML Full-text | XML Full-text
Abstract
This study was conducted for evaluation of the ability to maintain efficacy and biocompatibility of cross-linked dextran in hydroxypropyl methylcellulose (DiHM) and cross-linked dextran mixed with PMMA in hydroxypropyl methylcellulose (PDiHM), compared with hyaluronic acid (HA) filler. Saline and HA solution was administered [...] Read more.
This study was conducted for evaluation of the ability to maintain efficacy and biocompatibility of cross-linked dextran in hydroxypropyl methylcellulose (DiHM) and cross-linked dextran mixed with PMMA in hydroxypropyl methylcellulose (PDiHM), compared with hyaluronic acid (HA) filler. Saline and HA solution was administered in the negative and positive control groups, and DiHM and PDiHM were administered in the test groups (n = 10 in each group). The site of cranial subcutaneous injection was the mid-point of the interpupillary line, and the site of intraoral submucosal injection was the ridge crest 2 mm below the cervical line of the mandibular left incisor. Before and immediately after filler injection, intraoral photos and lateral cephalometric radiographs were taken for analysis and comparison of the effect of the filler on the injection sites. The filler injected areas were converted into sequential size changes (%) of the baseline. Histomorphologic examination was performed after 12 weeks. The smallest value in the filler injected area was observed during the experimental period in the normal saline group (p < 0.001), which was almost absorbed at 4 weeks (7.19% ± 12.72%). The HA group exhibited a steady decrease in sequential size and showed a lower value than the DiHM and PDiHM groups (saline < HA < DHiM, PDHiM, p < 0.001). DiHM and PDiHM tended to increase for the first 4 weeks and later decreased until 12 weeks. In this study on DiHM and PDiHM, there was no histological abnormality in cranial skin and oral mucosa. DiHM and PDiHM filler materials with injection system provide an excellent alternative surgical method for use in oral and craniofacial fields. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Application of Wnt Pathway Inhibitor Delivering Scaffold for Inhibiting Fibrosis in Urethra Strictures: In Vitro and in Vivo Study
Int. J. Mol. Sci. 2015, 16(11), 27659-27676; https://doi.org/10.3390/ijms161126050
Received: 22 September 2015 / Revised: 4 November 2015 / Accepted: 6 November 2015 / Published: 19 November 2015
Cited by 17 | PDF Full-text (7755 KB) | HTML Full-text | XML Full-text
Abstract
Objective: To evaluate the mechanical property and biocompatibility of the Wnt pathway inhibitor (ICG-001) delivering collagen/poly(l-lactide-co-caprolactone) (P(LLA-CL)) scaffold for urethroplasty, and also the feasibility of inhibiting the extracellular matrix (ECM) expression in vitro and in vivo. Methods: ICG-001 (1 mg [...] Read more.
Objective: To evaluate the mechanical property and biocompatibility of the Wnt pathway inhibitor (ICG-001) delivering collagen/poly(l-lactide-co-caprolactone) (P(LLA-CL)) scaffold for urethroplasty, and also the feasibility of inhibiting the extracellular matrix (ECM) expression in vitro and in vivo. Methods: ICG-001 (1 mg (2 mM)) was loaded into a (P(LLA-CL)) scaffold with the co-axial electrospinning technique. The characteristics of the mechanical property and drug release fashion of scaffolds were tested with a mechanical testing machine (Instron) and high-performance liquid chromatography (HPLC). Rabbit bladder epithelial cells and the dermal fibroblasts were isolated by enzymatic digestion method. (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay) and scanning electron microscopy (SEM) were used to evaluate the viability and proliferation of the cells on the scaffolds. Fibrolasts treated with TGF-β1 and ICG-001 released medium from scaffolds were used to evaluate the anti-fibrosis effect through immunofluorescence, real time PCR and western blot. Urethrography and histology were used to evaluate the efficacy of urethral implantation. Results: The scaffold delivering ICG-001 was fabricated, the fiber diameter and mechanical strength of scaffolds with inhibitor were comparable with the non-drug scaffold. The SEM and MTT assay showed no toxic effect of ICG-001 to the proliferation of epithelial cells on the collagen/P(LLA-CL) scaffold with ICG-001. After treatment with culture medium released from the drug-delivering scaffold, the expression of Collagen type 1, 3 and fibronectin of fibroblasts could be inhibited significantly at the mRNA and protein levels. In the results of urethrography, urethral strictures and fistulas were found in the rabbits treated with non-ICG-001 delivering scaffolds, but all the rabbits treated with ICG-001-delivering scaffolds showed wide caliber in urethras. Histology results showed less collagen but more smooth muscle and thicker epithelium in urethras repaired with ICG-001 delivering scaffolds. Conclusion: After loading with the Wnt signal pathway inhibitor ICG-001, the Collagen/P(LLA-CL) scaffold could facilitate a decrease in the ECM deposition of fibroblasts. The ICG-001 delivering Collagen/P(LLA-CL) nanofibrous scaffold seeded with epithelial cells has the potential to be a promising substitute material for urethroplasty. Longer follow-up study in larger animals is needed in the future. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
The Effect of Alendronate Loaded Biphasic Calcium Phosphate Scaffolds on Bone Regeneration in a Rat Tibial Defect Model
Int. J. Mol. Sci. 2015, 16(11), 26738-26753; https://doi.org/10.3390/ijms161125982
Received: 2 August 2015 / Revised: 22 October 2015 / Accepted: 27 October 2015 / Published: 6 November 2015
Cited by 12 | PDF Full-text (9717 KB) | HTML Full-text | XML Full-text
Abstract
This study investigated the effect of alendronate (Aln) released from biphasic calcium phosphate (BCP) scaffolds. We evaluated the in vitro osteogenic differentiation of Aln/BCP scaffolds using MG-63 cells and the in vivo bone regenerative capability of Aln/BCP scaffolds using a rat tibial defect [...] Read more.
This study investigated the effect of alendronate (Aln) released from biphasic calcium phosphate (BCP) scaffolds. We evaluated the in vitro osteogenic differentiation of Aln/BCP scaffolds using MG-63 cells and the in vivo bone regenerative capability of Aln/BCP scaffolds using a rat tibial defect model with radiography, micro-computed tomography (CT), and histological examination. In vitro studies included the surface morphology of BCP and Aln-loaded BCP scaffolds visualized using field-emission scanning electron microscope, release kinetics of Aln from BCP scaffolds, alkaline phosphatase (ALP) activity, calcium deposition, and gene expression. The in vitro studies showed that sustained release of Aln from the BCP scaffolds consisted of porous microstructures, and revealed that MG-63 cells cultured on Aln-loaded BCP scaffolds showed significantly increased ALP activity, calcium deposition, and gene expression compared to cells cultured on BCP scaffolds. The in vivo studies using radiograph and histology examination revealed abundant callus formation and bone maturation at the site in the Aln/BCP groups compared to the control group. However, solid bony bridge formation was not observed at plain radiographs until 8 weeks. Micro-CT analysis revealed that bone mineral density and bone formation volume were increased over time in an Aln concentration-dependent manner. These results suggested that Aln/BCP scaffolds have the potential for controlling the release of Aln and enhance bone formation and mineralization. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
The Effect of Interferon-γ and Zoledronate Treatment on Alpha-Tricalcium Phosphate/Collagen Sponge-Mediated Bone-Tissue Engineering
Int. J. Mol. Sci. 2015, 16(10), 25678-25690; https://doi.org/10.3390/ijms161025678
Received: 14 July 2015 / Revised: 15 October 2015 / Accepted: 15 October 2015 / Published: 26 October 2015
Cited by 3 | PDF Full-text (2151 KB) | HTML Full-text | XML Full-text
Abstract
Inflammatory responses are frequently associated with the expression of inflammatory cytokines and severe osteoclastogenesis, which significantly affect the efficacy of biomaterials. Recent findings have suggested that interferon (IFN)-γ and zoledronate (Zol) are effective inhibitors of osteoclastogenesis. However, little is known regarding the utility [...] Read more.
Inflammatory responses are frequently associated with the expression of inflammatory cytokines and severe osteoclastogenesis, which significantly affect the efficacy of biomaterials. Recent findings have suggested that interferon (IFN)-γ and zoledronate (Zol) are effective inhibitors of osteoclastogenesis. However, little is known regarding the utility of IFN-γ and Zol in bone tissue engineering. In this study, we generated rat models by generating critically sized defects in calvarias implanted with an alpha-tricalcium phosphate/collagen sponge (α-TCP/CS). At four weeks post-implantation, the rats were divided into IFN-γ, Zol, and control (no treatment) groups. Compared with the control group, the IFN-γ and Zol groups showed remarkable attenuation of severe osteoclastogenesis, leading to a significant enhancement in bone mass. Histomorphometric data and mRNA expression patterns in IFN-γ and Zol-injected rats reflected high bone-turnover with increased bone formation, a reduction in osteoclast numbers, and tumor necrosis factor-α expression. Our results demonstrated that the administration of IFN-γ and Zol enhanced bone regeneration of α-TCP/CS implants by enhancing bone formation, while hampering excess bone resorption. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Evaluating Osteogenic Potential of Ligamentum Flavum Cells Cultivated in Photoresponsive Hydrogel that Incorporates Bone Morphogenetic Protein-2 for Spinal Fusion
Int. J. Mol. Sci. 2015, 16(10), 23318-23336; https://doi.org/10.3390/ijms161023318
Received: 20 August 2015 / Revised: 8 September 2015 / Accepted: 22 September 2015 / Published: 28 September 2015
Cited by 2 | PDF Full-text (5971 KB) | HTML Full-text | XML Full-text
Abstract
Regenerative medicine is increasingly important in clinical practice. Ligamentum flava (LF) are typically removed during spine-related surgeries. LF may be a source of cells for spinal fusion that is conducted using tissue engineering techniques. In this investigation, LF cells of rabbits were isolated [...] Read more.
Regenerative medicine is increasingly important in clinical practice. Ligamentum flava (LF) are typically removed during spine-related surgeries. LF may be a source of cells for spinal fusion that is conducted using tissue engineering techniques. In this investigation, LF cells of rabbits were isolated and then characterized by flow cytometry, morphological observation, and immunofluorescence staining. The LF cells were also cultivated in polyethylene (glycol) diacrylate (PEGDA) hydrogels that incorporated bone morphogenetic protein-2 (BMP-2) growth factor, to evaluate their proliferation and secretion of ECM and differentiation in vitro. The experimental results thus obtained that the proliferation, ECM secretion, and differentiation of the PEGDA-BMP-2 group exceeded those of the PEGDA group during the period of cultivation. The mineralization and histological staining results differed similarly. A nude mice model was utilized to prove that LF cells on hydrogels could undergo osteogenic differentiation in vivo. These experimental results also revealed that the PEGDA-BMP-2 group had better osteogenic effects than the PEGDA group following a 12 weeks after transplantation. According to all of these experimental results, LF cells are a source of cells for spinal fusion and PEGDA-BMP-2 hydrogel is a candidate biomaterial for spinal fusion by tissue engineering. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Selenium-Substituted Hydroxyapatite/Biodegradable Polymer/Pamidronate Combined Scaffold for the Therapy of Bone Tumour
Int. J. Mol. Sci. 2015, 16(9), 22205-22222; https://doi.org/10.3390/ijms160922205
Received: 28 June 2015 / Revised: 20 August 2015 / Accepted: 25 August 2015 / Published: 14 September 2015
Cited by 6 | PDF Full-text (13382 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The present study evaluated a new concept of combined scaffolds as a promising bone replacement material for patients with a bone tumour or bone metastasis. The scaffolds were composed of hydroxyapatite doped with selenium ions and a biodegradable polymer (linear or branched), and [...] Read more.
The present study evaluated a new concept of combined scaffolds as a promising bone replacement material for patients with a bone tumour or bone metastasis. The scaffolds were composed of hydroxyapatite doped with selenium ions and a biodegradable polymer (linear or branched), and contained an active substance—bisphosphonate. For this purpose, a series of biodegradable polyesters were synthesized through a ring-opening polymerization of ε-caprolactone or d,l-lactide in the presence of 2-hydroxyethyl methacrylate (HEMA) or hyperbranched 2,2-bis(hydroxymethyl)propionic acid polyester-16-hydroxyl (bis-MPA) initiators, substances often used in the synthesis of medical materials. The polymers were obtained with a high yield and a number-average molecular weight up to 45,300 (g/mol). The combined scaffolds were then manufactured by a direct compression of pre-synthesized hydroxyapatite doped with selenite or selenate ions, obtained polymer and pamidronate as a model drug. It was found that the kinetic release of the drug from the scaffolds tested in vitro under physiological conditions is strongly dependent on the physicochemical properties and average molecular weight of the polymers. Furthermore, there was good correlation with the hydrolytic biodegradation results of the scaffolds fabricated without drug. The preliminary findings suggest that the fabricated combined scaffolds could be effectively used for the sustained delivery of bioactive molecules at bone defect sites. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Influence of Pre-Freezing Temperature on the Corneal Endothelial Cytocompatibility and Cell Delivery Performance of Porous Hyaluronic Acid Hydrogel Carriers
Int. J. Mol. Sci. 2015, 16(8), 18796-18811; https://doi.org/10.3390/ijms160818796
Received: 2 May 2015 / Revised: 21 July 2015 / Accepted: 31 July 2015 / Published: 11 August 2015
Cited by 4 | PDF Full-text (1981 KB) | HTML Full-text | XML Full-text
Abstract
The development of porous hyaluronic acid (HA) hydrogels for corneal endothelial tissue engineering is attractive because they can be used as functional cell delivery carriers to help in the reconstruction of damaged areas. The purpose of this study was to investigate the corneal [...] Read more.
The development of porous hyaluronic acid (HA) hydrogels for corneal endothelial tissue engineering is attractive because they can be used as functional cell delivery carriers to help in the reconstruction of damaged areas. The purpose of this study was to investigate the corneal endothelial cytocompatibility and cell delivery performance of porous HA hydrogel biomaterials fabricated at different pre-freezing temperatures. As compared to their counterparts prepared at −80 °C, the HA samples fabricated at higher pre-freezing temperature (i.e., 0 °C) exhibited a larger pore size and higher porosity, thereby leading to lower resistance to glucose permeation. Live/dead assays and gene expression analyses showed that the restricted porous structure of HA carriers decreases the viability and ionic pump function of cultured corneal endothelial cells (CECs). The results also indicated that the porous hydrogel biomaterials fabricated at high pre-freezing temperature seem to be more compatible with rabbit CECs. In an animal model of corneal endothelial dysfunction, the wounded rabbit corneas receiving bioengineered CEC sheets and restricted porous-structured HA carriers demonstrated poor tissue reconstruction. The therapeutic efficacy of cell sheet transplants can be improved by using carrier materials prepared at high pre-freezing temperature. Our findings suggest that the cryogenic operation temperature-mediated pore microstructure of HA carriers plays an important role in corneal endothelial cytocompatibility and cell delivery performance. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Differentiation Effects of Platelet-Rich Plasma Concentrations on Synovial Fluid Mesenchymal Stem Cells from Pigs Cultivated in Alginate Complex Hydrogel
Int. J. Mol. Sci. 2015, 16(8), 18507-18521; https://doi.org/10.3390/ijms160818507
Received: 22 January 2015 / Revised: 21 July 2015 / Accepted: 31 July 2015 / Published: 7 August 2015
Cited by 12 | PDF Full-text (4472 KB) | HTML Full-text | XML Full-text
Abstract
This article studied the effects of platelet-rich plasma (PRP) on the potential of synovial fluid mesenchymal stem cells (SF-MSCs) to differentiate. The PRP and SF-MSCs were obtained from the blood and knees of pigs, respectively. The identification of SF-MSCs and their ability to [...] Read more.
This article studied the effects of platelet-rich plasma (PRP) on the potential of synovial fluid mesenchymal stem cells (SF-MSCs) to differentiate. The PRP and SF-MSCs were obtained from the blood and knees of pigs, respectively. The identification of SF-MSCs and their ability to differentiate were studied by histological and surface epitopes, respectively. The SF-MSCs can undergo trilineage mesenchymal differentiation under osteogenic, chondrogenic, and adipocyte induction. The effects of various PRP concentrations (0%, 20% and 50% PRP) on differentiation were evaluated using the SF-MSCs-alginate system, such as gene expression and DNA proliferation. A 50% PRP concentration yielded better differentiation than the 20% PRP concentration. PRP favored the chondrogenesis of SF-MSCs over their osteogenesis in a manner that depended on the ratios of type II collagen/type I collagen and aggrecan/osteopontin. Eventually, PRP promoted the proliferation of SF-MSCs and induced chondrogenic differentiation of SF-MSCs in vitro. Both PRP and SF-MSCs could be feasibly used in regenerative medicine and orthopedic surgeries. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Effect of rhBMP-2 Immobilized Anorganic Bovine Bone Matrix on Bone Regeneration
Int. J. Mol. Sci. 2015, 16(7), 16034-16052; https://doi.org/10.3390/ijms160716034
Received: 22 April 2015 / Revised: 24 June 2015 / Accepted: 7 July 2015 / Published: 14 July 2015
Cited by 10 | PDF Full-text (12495 KB) | HTML Full-text | XML Full-text
Abstract
Anorganic bovine bone matrix (Bio-Oss®) has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been suggested to overcome this limitation of Bio-Oss®. [...] Read more.
Anorganic bovine bone matrix (Bio-Oss®) has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter) were formed in a white rabbit model and then implanted or not (controls) with Bio-Oss® or BMP-2/Bio-Oss®. The Bio-Oss® and BMP-2/Bio-Oss® groups had significantly greater new bone areas (expressed as percentages of augmented areas) than the non-implanted controls at four and eight weeks after surgery, and the BMP-2/Bio-Oss® group (16.50 ± 2.87 (n = 6)) had significantly greater new bone areas than the Bio-Oss® group (9.43 ± 3.73 (n = 6)) at four weeks. These findings suggest that rhBMP-2 treated heparinized Bio-Oss® markedly enhances bone regeneration. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration
Int. J. Mol. Sci. 2015, 16(7), 15118-15135; https://doi.org/10.3390/ijms160715118
Received: 25 April 2015 / Revised: 3 June 2015 / Accepted: 30 June 2015 / Published: 3 July 2015
Cited by 95 | PDF Full-text (3172 KB) | HTML Full-text | XML Full-text
Abstract
Painful degeneration of soft tissues accounts for high socioeconomic costs. Tissue engineering aims to provide biomimetics recapitulating native tissues. Biocompatible thermoplastics for 3D printing can generate high-resolution structures resembling tissue extracellular matrix. Large-pore 3D-printed acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA) scaffolds [...] Read more.
Painful degeneration of soft tissues accounts for high socioeconomic costs. Tissue engineering aims to provide biomimetics recapitulating native tissues. Biocompatible thermoplastics for 3D printing can generate high-resolution structures resembling tissue extracellular matrix. Large-pore 3D-printed acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA) scaffolds were compared for cell ingrowth, viability, and tissue generation. Primary articular chondrocytes and nucleus pulposus (NP) cells were cultured on ABS and PLA scaffolds for three weeks. Both cell types proliferated well, showed high viability, and produced ample amounts of proteoglycan and collagen type II on both scaffolds. NP generated more matrix than chondrocytes; however, no difference was observed between scaffold types. Mechanical testing revealed sustained scaffold stability. This study demonstrates that chondrocytes and NP cells can proliferate on both ABS and PLA scaffolds printed with a simplistic, inexpensive desktop 3D printer. Moreover, NP cells produced more proteoglycan than chondrocytes, irrespective of thermoplastic type, indicating that cells maintain individual phenotype over the three-week culture period. Future scaffold designs covering larger pore sizes and better mimicking native tissue structure combined with more flexible or resorbable materials may provide implantable constructs with the proper structure, function, and cellularity necessary for potential cartilage and disc tissue repair in vivo. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Biomineral/Agarose Composite Gels Enhance Proliferation of Mesenchymal Stem Cells with Osteogenic Capability
Int. J. Mol. Sci. 2015, 16(6), 14245-14258; https://doi.org/10.3390/ijms160614245
Received: 22 March 2015 / Revised: 10 June 2015 / Accepted: 16 June 2015 / Published: 23 June 2015
Cited by 10 | PDF Full-text (2824 KB) | HTML Full-text | XML Full-text
Abstract
Hydroxyapatite (HA) or calcium carbonate (CaCO3) formed on an organic polymer of agarose gel is a biomaterial that can be used for bone tissue regeneration. However, in critical bone defects, the regeneration capability of these materials is limited. Mesenchymal stem cells [...] Read more.
Hydroxyapatite (HA) or calcium carbonate (CaCO3) formed on an organic polymer of agarose gel is a biomaterial that can be used for bone tissue regeneration. However, in critical bone defects, the regeneration capability of these materials is limited. Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into bone forming osteoblasts. In this study, we loaded MSCs on HA- or CaCO3-formed agarose gel and cultured them with dexamethasone, which triggers the osteogenic differentiation of MSCs. High alkaline phosphatase activity was detected on both the HA- and CaCO3-formed agarose gels; however, basal activity was only detected on bare agarose gel. Bone-specific osteocalcin content was detected on CaCO3-formed agarose gel on Day 14 of culture, and levels subsequently increased over time. Similar osteocalcin content was detected on HA-formed agarose on Day 21 and levels increased on Day 28. In contrast, only small amounts of osteocalcin were found on bare agarose gel. Consequently, osteogenic capability of MSCs was enhanced on CaCO3-formed agarose at an early stage, and both HA- and CaCO3-formed agarose gels well supported the capability at a later stage. Therefore, MSCs loaded on either HA- or CaCO3-formed agarose could potentially be employed for the repair of critical bone defects. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model
Int. J. Mol. Sci. 2015, 16(6), 12616-12630; https://doi.org/10.3390/ijms160612616
Received: 22 March 2015 / Revised: 20 April 2015 / Accepted: 26 May 2015 / Published: 4 June 2015
Cited by 10 | PDF Full-text (2113 KB) | HTML Full-text | XML Full-text
Abstract
The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to [...] Read more.
The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone) seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step) or only after six weeks of subcutaneous “incubation” (2-step). After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
A Solid-State NMR Study of Selenium Substitution into Nanocrystalline Hydroxyapatite
Int. J. Mol. Sci. 2015, 16(5), 11452-11464; https://doi.org/10.3390/ijms160511452
Received: 1 March 2015 / Revised: 9 April 2015 / Accepted: 29 April 2015 / Published: 19 May 2015
Cited by 12 | PDF Full-text (872 KB) | HTML Full-text | XML Full-text
Abstract
The substitution of selenium oxyanions in the hydroxyapatite structure was examined using multinuclear solid-state resonance spectroscopy (ssNMR). The study was supported by powder X-ray diffractometry (PXRD) and wavelength dispersion X-ray fluorescence (WD-XRF). Samples of pure hydroxyapatite (HA300) and selenate (HA300 [...] Read more.
The substitution of selenium oxyanions in the hydroxyapatite structure was examined using multinuclear solid-state resonance spectroscopy (ssNMR). The study was supported by powder X-ray diffractometry (PXRD) and wavelength dispersion X-ray fluorescence (WD-XRF). Samples of pure hydroxyapatite (HA300) and selenate (HA300-1.2SeO4) or selenite (HA300-1.2SeO3) substituted hydroxyapatites were synthesized using the standard wet method and heated at 300 °C to remove loosely bonded water. PXRD data showed that all samples are single-phase, nanocrystalline hydroxyapatite. The incorporation of selenite and selenate ions affected the lattice constants. In selenium-containing samples the concentration of Se was very similar and amounted to 9.55% and 9.64%, for HA300-1.2SeO4 and HA300-1.2SeO3, respectively. PXRD and ssNMR data showed that the selenite doping significantly decreases the crystallite size and crystallinity degree. 31P and 1H NMR experiments demonstrated the developed surface hydrated layer in all samples, especially in HA300-1.2SeO3. 1H NMR studies showed the dehydroxylation of HA during the selenium oxyanions substitution and the existence of hydrogen bonding in structural hydroxyl group channels. 1H→77Se cross polarization NMR experiments indicated that selenites and selenates are located in the crystal lattice and on the crystal surface. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Cell Adhesion and in Vivo Osseointegration of Sandblasted/Acid Etched/Anodized Dental Implants
Int. J. Mol. Sci. 2015, 16(5), 10324-10336; https://doi.org/10.3390/ijms160510324
Received: 25 March 2015 / Revised: 8 April 2015 / Accepted: 29 April 2015 / Published: 6 May 2015
Cited by 25 | PDF Full-text (7861 KB) | HTML Full-text | XML Full-text
Abstract
The authors describe a new type of titanium (Ti) implant as a Modi-anodized (ANO) Ti implant, the surface of which was treated by sandblasting, acid etching (SLA), and anodized techniques. The aim of the present study was to evaluate the adhesion of MG-63 [...] Read more.
The authors describe a new type of titanium (Ti) implant as a Modi-anodized (ANO) Ti implant, the surface of which was treated by sandblasting, acid etching (SLA), and anodized techniques. The aim of the present study was to evaluate the adhesion of MG-63 cells to Modi-ANO surface treated Ti in vitro and to investigate its osseointegration characteristics in vivo. Four different types of Ti implants were examined, that is, machined Ti (control), SLA, anodized, and Modi-ANO Ti. In the cell adhesion study, Modi-ANO Ti showed higher initial MG-63 cell adhesion and induced greater filopodia growth than other groups. In vivo study in a beagle model revealed the bone-to-implant contact (BIC) of Modi-ANO Ti (74.20% ± 10.89%) was much greater than those of machined (33.58% ± 8.63%), SLA (58.47% ± 12.89), or ANO Ti (59.62% ± 18.30%). In conclusion, this study demonstrates that Modi-ANO Ti implants produced by sandblasting, acid etching, and anodizing improve cell adhesion and bone ongrowth as compared with machined, SLA, or ANO Ti implants. These findings suggest that the application of Modi-ANO surface treatment could improve the osseointegration of dental implant. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Area-Specific Cell Stimulation via Surface-Mediated Gene Transfer Using Apatite-Based Composite Layers
Int. J. Mol. Sci. 2015, 16(4), 8294-8309; https://doi.org/10.3390/ijms16048294
Received: 18 November 2014 / Revised: 27 March 2015 / Accepted: 30 March 2015 / Published: 14 April 2015
Cited by 1 | PDF Full-text (1195 KB) | HTML Full-text | XML Full-text
Abstract
Surface-mediated gene transfer systems using biocompatible calcium phosphate (CaP)-based composite layers have attracted attention as a tool for controlling cell behaviors. In the present study we aimed to demonstrate the potential of CaP-based composite layers to mediate area-specific dual gene transfer and to [...] Read more.
Surface-mediated gene transfer systems using biocompatible calcium phosphate (CaP)-based composite layers have attracted attention as a tool for controlling cell behaviors. In the present study we aimed to demonstrate the potential of CaP-based composite layers to mediate area-specific dual gene transfer and to stimulate cells on an area-by-area basis in the same well. For this purpose we prepared two pairs of DNA–fibronectin–apatite composite (DF-Ap) layers using a pair of reporter genes and pair of differentiation factor genes. The results of the area-specific dual gene transfer successfully demonstrated that the cells cultured on a pair of DF-Ap layers that were adjacently placed in the same well showed specific gene expression patterns depending on the gene that was immobilized in theunderlying layer. Moreover, preliminary real-time PCR results indicated that multipotential C3H10T1/2 cells may have a potential to change into different types of cells depending on the differentiation factor gene that was immobilized in the underlying layer, even in the same well. Because DF-Ap layers have a potential to mediate area-specific cell stimulation on their surfaces, they could be useful in tissue engineering applications. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Synthesis of Spongy-Like Mesoporous Hydroxyapatite from Raw Waste Eggshells for Enhanced Dissolution of Ibuprofen Loaded via Supercritical CO2
Int. J. Mol. Sci. 2015, 16(4), 7960-7975; https://doi.org/10.3390/ijms16047960
Received: 3 February 2015 / Revised: 31 March 2015 / Accepted: 3 April 2015 / Published: 9 April 2015
Cited by 16 | PDF Full-text (1992 KB) | HTML Full-text | XML Full-text
Abstract
The use of cheaper and recyclable biomaterials (like eggshells) to synthesize high purity hydroxyapatite (HAp) with better properties (small particle size, large surface area and pore volume) for applications (in environmental remediation, bone augmentation and replacement, and drug delivery systems) is vital since [...] Read more.
The use of cheaper and recyclable biomaterials (like eggshells) to synthesize high purity hydroxyapatite (HAp) with better properties (small particle size, large surface area and pore volume) for applications (in environmental remediation, bone augmentation and replacement, and drug delivery systems) is vital since high-purity synthetic calcium sources are expensive. In this work, pure and mesoporous HAp nanopowder with large pore volume (1.4 cm3/g) and surface area (284.1 m2/g) was produced from raw eggshells at room temperature using a simple two-step procedure. The control of precursor droplets could stabilize the pH value of the reaction solution, because of the size of the needle (of the syringe pump used for precursor additions) leading to production of HAp with high surface area and pore size. The as-produced HAp revealed high ibuprofen (as a model drug) loading (1.38 g/g HAp), enhanced dissolution and controllable release of the drug via solute-saturated supercritical carbon dioxide. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Multi-Layer Electrospun Membrane Mimicking Tendon Sheath for Prevention of Tendon Adhesions
Int. J. Mol. Sci. 2015, 16(4), 6932-6944; https://doi.org/10.3390/ijms16046932
Received: 3 February 2015 / Revised: 8 March 2015 / Accepted: 23 March 2015 / Published: 26 March 2015
Cited by 14 | PDF Full-text (1800 KB) | HTML Full-text | XML Full-text
Abstract
Defect of the tendon sheath after tendon injury is a main reason for tendon adhesions, but it is a daunting challenge for the biomimetic substitute of the tendon sheath after injury due to its multi-layer membrane-like structure and complex biologic functions. In this [...] Read more.
Defect of the tendon sheath after tendon injury is a main reason for tendon adhesions, but it is a daunting challenge for the biomimetic substitute of the tendon sheath after injury due to its multi-layer membrane-like structure and complex biologic functions. In this study, a multi-layer membrane with celecoxib-loaded poly(l-lactic acid)-polyethylene glycol (PELA) electrospun fibrous membrane as the outer layer, hyaluronic acid (HA) gel as middle layer, and PELA electrospun fibrous membrane as the inner layer was designed. The anti-adhesion efficacy of this multi-layer membrane was compared with a single-layer use in rabbit flexor digitorum profundus tendon model. The surface morphology showed that both PELA fibers and celecoxib-loaded PELA fibers in multi-layer membrane were uniform in size, randomly arrayed, very porous, and smooth without beads. Multi-layer membrane group had fewer peritendinous adhesions and better gliding than the PELA membrane group and control group in gross and histological observation. The similar mechanical characteristic and collagen expression of tendon repair site in the three groups indicated that the multi-layer membrane did not impair tendon healing. Taken together, our results demonstrated that such a biomimetic multi-layer sheath could be used as a potential strategy in clinics for promoting tendon gliding and preventing adhesion without poor tendon healing. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
In Vitro Corrosion and Cytocompatibility Properties of Nano-Whisker Hydroxyapatite Coating on Magnesium Alloy for Bone Tissue Engineering Applications
Int. J. Mol. Sci. 2015, 16(3), 6113-6123; https://doi.org/10.3390/ijms16036113
Received: 15 December 2014 / Revised: 19 January 2015 / Accepted: 17 February 2015 / Published: 17 March 2015
Cited by 9 | PDF Full-text (5110 KB) | HTML Full-text | XML Full-text
Abstract
We report here the successful fabrication of nano-whisker hydroxyapatite (nHA) coatings on Mg alloy by using a simple one-step hydrothermal process in aqueous solution. The nHA coating shows uniform structure and high crystallinity. Results indicate that nHA coating is promising for improving the [...] Read more.
We report here the successful fabrication of nano-whisker hydroxyapatite (nHA) coatings on Mg alloy by using a simple one-step hydrothermal process in aqueous solution. The nHA coating shows uniform structure and high crystallinity. Results indicate that nHA coating is promising for improving the in vitro corrosion and cytocompatibility properties of Mg-based implants and devices for bone tissue engineering. In addition, the simple hydrothermal deposition method used in the current study is also applicable to substrates with complex shapes or surface geometries. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Biomechanical Evaluation of Ti-Nb-Sn Alloy Implants with a Low Young’s Modulus
Int. J. Mol. Sci. 2015, 16(3), 5779-5788; https://doi.org/10.3390/ijms16035779
Received: 25 November 2014 / Revised: 9 February 2015 / Accepted: 4 March 2015 / Published: 12 March 2015
Cited by 8 | PDF Full-text (1680 KB) | HTML Full-text | XML Full-text
Abstract
Dental implants are widely used and are a predictable treatment in various edentulous cases. Occlusal overload may be causally related to implant bone loss and a loss of integration. Stress concentrations may be diminished using a mechanobiologically integrated implant with bone tissue. The [...] Read more.
Dental implants are widely used and are a predictable treatment in various edentulous cases. Occlusal overload may be causally related to implant bone loss and a loss of integration. Stress concentrations may be diminished using a mechanobiologically integrated implant with bone tissue. The purpose of this study was to investigate the biomechanical behavior, biocompatibility and bioactivity of a Ti-Nb-Sn alloy as a dental implant material. It was compared with cpTi. Cell proliferation and alkaline phosphatase (ALP) activity were quantified. To assess the degree of osseointegration, a push-in test was carried out. Cell proliferation and ALP activity in the cells grown on prepared surfaces were similar for the Ti-Nb-Sn alloy and for cpTi in all the experiments. A comparison between the Ti-Nb-Sn alloy implant and the cpTi implant revealed that no significant difference was apparent for the push-in test values. These results suggest that implants fabricated using Ti-Nb-Sn have a similar biological potential as cpTi and are capable of excellent osseointegration. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Novel Cholesterol-Based Cationic Lipids as Transfecting Agents of DNA for Efficient Gene Delivery
Int. J. Mol. Sci. 2015, 16(3), 5666-5681; https://doi.org/10.3390/ijms16035666
Received: 12 January 2015 / Revised: 29 January 2015 / Accepted: 13 February 2015 / Published: 11 March 2015
Cited by 10 | PDF Full-text (3352 KB) | HTML Full-text | XML Full-text
Abstract
The design, synthesis and biological evaluation of the cationic lipid gene delivery vectors based on cholesterol and natural amino acids lysine or histidine are described. Cationic liposomes composed of the newly synthesized cationic lipids 1a or 1b and neutral lipid DOPE (1,2-dioleoyl-l-α-glycero-3-phosphatidyl-ethanolamine) exhibited [...] Read more.
The design, synthesis and biological evaluation of the cationic lipid gene delivery vectors based on cholesterol and natural amino acids lysine or histidine are described. Cationic liposomes composed of the newly synthesized cationic lipids 1a or 1b and neutral lipid DOPE (1,2-dioleoyl-l-α-glycero-3-phosphatidyl-ethanolamine) exhibited good transfection efficiency. pEGFP-N1 plasmid DNA was transferred into 293T cells by cationic liposomes formed from cationic lipids 1a and 1b, and the transfection activity of the cationic lipids was superior (1a) or parallel (1b) to that of the commercially available 3β-[N-(N',N'-dimethylaminoethyl)-carbamoyl] cholesterol (DC-Chol) derived from the same cholesterol backbone with different head groups. Combined with the results of agarose gel electrophoresis, transfection experiments with various molar ratios of the cationic lipids and DOPE and N/P (+/−) molar charge ratios, a more effective formulation was formed, which could lead to relatively high transfection efficiency. Cationic lipid 1a represents a potential agent for the liposome used in gene delivery due to low cytotoxicity and impressive gene transfection activity. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Effect of Platelet-Rich Plasma and Bioactive Glass Powder for the Improvement of Rotator Cuff Tendon-to-Bone Healing in a Rabbit Model
Int. J. Mol. Sci. 2014, 15(12), 21980-21991; https://doi.org/10.3390/ijms151221980
Received: 7 October 2014 / Revised: 13 November 2014 / Accepted: 25 November 2014 / Published: 28 November 2014
Cited by 7 | PDF Full-text (2122 KB) | HTML Full-text | XML Full-text
Abstract
To test the hypothesis that a platelet-rich plasma (PRP) plus bioactive glass (BG) mixture could shorten the tendon-bone healing process in rotator cuff tendon repair, thirty mature male New Zealand white rabbits were randomly divided into three groups, Control, PRP, and PRP + [...] Read more.
To test the hypothesis that a platelet-rich plasma (PRP) plus bioactive glass (BG) mixture could shorten the tendon-bone healing process in rotator cuff tendon repair, thirty mature male New Zealand white rabbits were randomly divided into three groups, Control, PRP, and PRP + BG. All groups underwent a surgical procedure to establish a rotator cuff tendon healing model. Mechanical examinations and histological assays were taken to verify the adhesion of the tendon-bone. Real-time PCR was adopted to analyze Bone Morphogenetic Protein-2 (BMP-2). The maximum load-to-failure value in mechanical examinations was significantly higher in the PRP + BG group than that in the control group after six weeks (Control 38.73 ± 8.58, PRP 54.49 ± 8.72, PRP + BG 79.15 ± 7.62, p < 0.001), but it was not significantly different at 12 weeks (PRP 74.27 ± 7.74, PRP + BG 82.57 ± 6.63, p = 0.145). In histological assays, H&E (hematoxylin-eosin) staining showed that the interface between the tendon-bone integration was much sturdier in the PRP + BG group compared to the other two groups at each time point, and more ordered arranged tendon fibers can be seen at 12 weeks. At six weeks, the mRNA expression levels of BMP-2 in the PRP + BG group were higher than those in the other groups (PRP + BG 0.65 ± 0.11, PRP 2.284 ± 0.07, Control 0.12 ± 0.05, p < 0.05). However, there was no significant difference in the mRNA expression levels of BMP-2 among the three groups at 12 weeks (p = 0.922, 0.067, 0.056). BMP-2 levels in PRP and PRP+BG groups were significantly lower at 12 weeks compared to six weeks (p = 0.006, <0.001).We found that the PRP + BG mixture could enhance tendon-bone healing in rotator cuff tendon repair. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessArticle
Mechanical Reinforcement of Diopside Bone Scaffolds with Carbon Nanotubes
Int. J. Mol. Sci. 2014, 15(10), 19319-19329; https://doi.org/10.3390/ijms151019319
Received: 5 September 2014 / Revised: 23 September 2014 / Accepted: 15 October 2014 / Published: 23 October 2014
Cited by 9 | PDF Full-text (5532 KB) | HTML Full-text | XML Full-text
Abstract
Carbon nanotubes are ideal candidates for the mechanical reinforcement of ceramic due to their excellent mechanical properties, high aspect ratio and nanometer scale diameter. In this study, the effects of multi-walled carbon nanotubes (MWCNTs) on the mechanical properties of diopside (Di) scaffolds fabricated [...] Read more.
Carbon nanotubes are ideal candidates for the mechanical reinforcement of ceramic due to their excellent mechanical properties, high aspect ratio and nanometer scale diameter. In this study, the effects of multi-walled carbon nanotubes (MWCNTs) on the mechanical properties of diopside (Di) scaffolds fabricated by selective laser sintering were investigated. Results showed that compressive strength and fracture toughness improved significantly with increasing MWCNTs from 0.5 to 2 wt %, and then declined with increasing MWCNTs to 5 wt %. Compressive strength and fracture toughness were enhanced by 106% and 21%, respectively. The reinforcing mechanisms were identified as crack deflection, MWCNTs crack bridging and pull-out. Further, the scaffolds exhibited good apatite-formation ability and supported adhesion and proliferation of cells in vitro. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Review

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Open AccessReview
Hydrogels for Engineering of Perfusable Vascular Networks
Int. J. Mol. Sci. 2015, 16(7), 15997-16016; https://doi.org/10.3390/ijms160715997
Received: 1 April 2015 / Revised: 9 June 2015 / Accepted: 7 July 2015 / Published: 14 July 2015
Cited by 27 | PDF Full-text (891 KB) | HTML Full-text | XML Full-text
Abstract
Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such [...] Read more.
Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessReview
Biomedical Application of Low Molecular Weight Heparin/Protamine Nano/Micro Particles as Cell- and Growth Factor-Carriers and Coating Matrix
Int. J. Mol. Sci. 2015, 16(5), 11785-11803; https://doi.org/10.3390/ijms160511785
Received: 11 March 2015 / Revised: 7 May 2015 / Accepted: 15 May 2015 / Published: 22 May 2015
Cited by 9 | PDF Full-text (3920 KB) | HTML Full-text | XML Full-text
Abstract
Low molecular weight heparin (LMWH)/protamine (P) nano/micro particles (N/MPs) (LMWH/P N/MPs) were applied as carriers for heparin-binding growth factors (GFs) and for adhesive cells including adipose-derived stromal cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs). A mixture of LMWH and P yields [...] Read more.
Low molecular weight heparin (LMWH)/protamine (P) nano/micro particles (N/MPs) (LMWH/P N/MPs) were applied as carriers for heparin-binding growth factors (GFs) and for adhesive cells including adipose-derived stromal cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs). A mixture of LMWH and P yields a dispersion of N/MPs (100 nm–3 μm in diameter). LMWH/P N/MPs can be immobilized onto cell surfaces or extracellular matrix, control the release, activate GFs and protect various GFs. Furthermore, LMWH/P N/MPs can also bind to adhesive cell surfaces, inducing cells and LMWH/P N/MPs-aggregate formation. Those aggregates substantially promoted cellular viability, and induced vascularization and fibrous tissue formation in vivo. The LMWH/P N/MPs, in combination with ADSCs or BMSCs, are effective cell-carriers and are potential promising novel therapeutic agents for inducing vascularization and fibrous tissue formation in ischemic disease by transplantation of the ADSCs and LMWH/P N/MPs-aggregates. LMWH/P N/MPs can also bind to tissue culture plates and adsorb exogenous GFs or GFs from those cells. The LMWH/P N/MPs-coated matrix in the presence of GFs may provide novel biomaterials that can control cellular activity such as growth and differentiation. Furthermore, three-dimensional (3D) cultures of cells including ADSCs and BMSCs using plasma-medium gel with LMWH/P N/MPs exhibited efficient cell proliferation. Thus, LMWH/P N/MPs are an adequate carrier both for GFs and for stromal cells such as ADSCs and BMSCs, and are a functional coating matrix for their cultures. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessReview
Three-Dimensional Cell Culture: A Breakthrough in Vivo
Int. J. Mol. Sci. 2015, 16(3), 5517-5527; https://doi.org/10.3390/ijms16035517
Received: 17 December 2014 / Revised: 13 February 2015 / Accepted: 5 March 2015 / Published: 11 March 2015
Cited by 181 | PDF Full-text (1118 KB) | HTML Full-text | XML Full-text
Abstract
Cell culture is an important tool for biological research. Two-dimensional cell culture has been used for some time now, but growing cells in flat layers on plastic surfaces does not accurately model the in vivo state. As compared to the two-dimensional case, the [...] Read more.
Cell culture is an important tool for biological research. Two-dimensional cell culture has been used for some time now, but growing cells in flat layers on plastic surfaces does not accurately model the in vivo state. As compared to the two-dimensional case, the three-dimensional (3D) cell culture allows biological cells to grow or interact with their surroundings in all three dimensions thanks to an artificial environment. Cells grown in a 3D model have proven to be more physiologically relevant and showed improvements in several studies of biological mechanisms like: cell number monitoring, viability, morphology, proliferation, differentiation, response to stimuli, migration and invasion of tumor cells into surrounding tissues, angiogenesis stimulation and immune system evasion, drug metabolism, gene expression and protein synthesis, general cell function and in vivo relevance. 3D culture models succeed thanks to technological advances, including materials science, cell biology and bioreactor design. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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Open AccessReview
Methods for Biomimetic Remineralization of Human Dentine: A Systematic Review
Int. J. Mol. Sci. 2015, 16(3), 4615-4627; https://doi.org/10.3390/ijms16034615
Received: 9 January 2015 / Revised: 6 February 2015 / Accepted: 16 February 2015 / Published: 2 March 2015
Cited by 21 | PDF Full-text (725 KB) | HTML Full-text | XML Full-text
Abstract
This study aimed to review the laboratory methods on biomimetic remineralization of demineralized human dentine. A systematic search of the publications in the PubMed, TRIP, and Web of Science databases was performed. Titles and abstracts of initially identified publications were screened. Clinical trials, [...] Read more.
This study aimed to review the laboratory methods on biomimetic remineralization of demineralized human dentine. A systematic search of the publications in the PubMed, TRIP, and Web of Science databases was performed. Titles and abstracts of initially identified publications were screened. Clinical trials, reviews, non-English articles, resin-dentine interface studies, hybrid layer studies, hybrid scaffolds studies, and irrelevant studies were excluded. The remaining papers were retrieved with full texts. Manual screening was conducted on the bibliographies of remaining papers to identify relevant articles. A total of 716 studies were found, and 690 were excluded after initial screening. Two articles were identified from the bibliographies of the remaining papers. After retrieving the full text, 23 were included in this systematic review. Sixteen studies used analogues to mimic the functions of non-collagenous proteins in biomineralization of dentine, and four studies used bioactive materials to induce apatite formation on demineralized dentine surface. One study used zinc as a bioactive element, one study used polydopamine, and another study constructed an agarose hydrogel system for biomimetic mineralization of dentine. Many studies reported success in biomimetic mineralization of dentine, including the use of non-collagenous protein analogues, bioactive materials, or elements and agarose hydrogel system. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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