Pub Date : 2019-12-09DOI: 10.1088/1748-605X/ab4f8b
S. Jaiswal, Anshu Dubey, Swati Haldar, P. Roy, D. Lahiri
The interaction of proteins with implantable metallic surfaces has a great influence on the bioactivity and biodegradation of orthopaedic implants. Initial osseointegration is known to be critical for the long term success of orthopaedic implants. The surface properties of the implant and electrochemical milieu of the surrounding solution such as electrostatic, hydrophobic, and hydrogen bonding interactions significantly modulate protein adsorption by implants. Magnesium (Mg) is considered to improve the adhesion of osteoblasts via ligand binding of the integrin receptors. Mg-based composites, reinforced with hydroxyapatite (HA), are potential candidates for temporary orthopaedic implants. However, their clinical translation requires enhanced degradation resistance in physiological environment so that it is in sync with the healing rate of the bone. The present study deals with the protein adsorption characteristics and degradation behaviour of Mg-HA-based biodegradable implants. Quantitative analysis of apatite inducing ability of composites was evaluated in terms of mass gain in simulated body fluid (SBF) as well as in foetal bovine serum (FBS), by an in vitro immersion study. Incorporation of 5 and 15 wt% HA to Mg-3Zn improved apatite formation up to 35% and 66%, respectively, after 14 days of immersion in SBF. Compared to FBS, SBF is found to be significantly more effective in precipitating apatite on a Mg-HA surface. However, FBS offered more corrosion resistance to Mg-HA than SBF did, as evident from the significant differences in the protein adhesion capabilities of the composite surface when incubated separately in these two mediums. The addition of 15 wt% HA enhanced the protein adsorption capability by ∼35%. These studies highlight the possibility of modulating the degradation and bioactivity of Mg-based composite by tailoring the composition of HA. These findings, in turn, warrant the suitability of Mg-HA composite in orthopaedic application.
{"title":"Differential in vitro degradation and protein adhesion behaviour of spark plasma sintering fabricated magnesium-based temporary orthopaedic implant in serum and simulated body fluid","authors":"S. Jaiswal, Anshu Dubey, Swati Haldar, P. Roy, D. Lahiri","doi":"10.1088/1748-605X/ab4f8b","DOIUrl":"https://doi.org/10.1088/1748-605X/ab4f8b","url":null,"abstract":"The interaction of proteins with implantable metallic surfaces has a great influence on the bioactivity and biodegradation of orthopaedic implants. Initial osseointegration is known to be critical for the long term success of orthopaedic implants. The surface properties of the implant and electrochemical milieu of the surrounding solution such as electrostatic, hydrophobic, and hydrogen bonding interactions significantly modulate protein adsorption by implants. Magnesium (Mg) is considered to improve the adhesion of osteoblasts via ligand binding of the integrin receptors. Mg-based composites, reinforced with hydroxyapatite (HA), are potential candidates for temporary orthopaedic implants. However, their clinical translation requires enhanced degradation resistance in physiological environment so that it is in sync with the healing rate of the bone. The present study deals with the protein adsorption characteristics and degradation behaviour of Mg-HA-based biodegradable implants. Quantitative analysis of apatite inducing ability of composites was evaluated in terms of mass gain in simulated body fluid (SBF) as well as in foetal bovine serum (FBS), by an in vitro immersion study. Incorporation of 5 and 15 wt% HA to Mg-3Zn improved apatite formation up to 35% and 66%, respectively, after 14 days of immersion in SBF. Compared to FBS, SBF is found to be significantly more effective in precipitating apatite on a Mg-HA surface. However, FBS offered more corrosion resistance to Mg-HA than SBF did, as evident from the significant differences in the protein adhesion capabilities of the composite surface when incubated separately in these two mediums. The addition of 15 wt% HA enhanced the protein adsorption capability by ∼35%. These studies highlight the possibility of modulating the degradation and bioactivity of Mg-based composite by tailoring the composition of HA. These findings, in turn, warrant the suitability of Mg-HA composite in orthopaedic application.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab4f8b","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47515598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-09DOI: 10.1088/1748-605X/ab52db
J. Musilkova, E. Filová, J. Pala, R. Matějka, D. Hadraba, David Vondrášek, Ondřej Kaplan, T. Riedel, E. Brynda, Johanka Kučerová, M. Konarik, F. Lopot, Jan Pirk, L. Bačáková
Decellularized human pericardium is under study as an allogenic material for cardiovascular applications. The effects of crosslinking on the mechanical properties of decellularized pericardium were determined with a uniaxial tensile test, and the effects of crosslinking on the collagen structure of decellularized pericardium were determined by multiphoton microscopy. The viability of human umbilical vein endothelial cells seeded on decellularized human pericardium and on pericardium strongly and weakly crosslinked with glutaraldehyde and with genipin was evaluated by means of an MTS assay. The viability of the cells, measured by their metabolic activity, decreased considerably when the pericardium was crosslinked with glutaraldehyde. Conversely, the cell viability increased when the pericardium was crosslinked with genipin. Coating both non-modified pericardium and crosslinked pericardium with a fibrin mesh or with a mesh containing attached heparin and/or fibronectin led to a significant increase in cell viability. The highest degree of viability was attained for samples that were weakly crosslinked with genipin and modified by means of a fibrin and fibronectin coating. The results indicate a method by which in vivo endothelialization of human cardiac allografts or xenografts could potentially be encouraged.
{"title":"Human decellularized and crosslinked pericardium coated with bioactive molecular assemblies","authors":"J. Musilkova, E. Filová, J. Pala, R. Matějka, D. Hadraba, David Vondrášek, Ondřej Kaplan, T. Riedel, E. Brynda, Johanka Kučerová, M. Konarik, F. Lopot, Jan Pirk, L. Bačáková","doi":"10.1088/1748-605X/ab52db","DOIUrl":"https://doi.org/10.1088/1748-605X/ab52db","url":null,"abstract":"Decellularized human pericardium is under study as an allogenic material for cardiovascular applications. The effects of crosslinking on the mechanical properties of decellularized pericardium were determined with a uniaxial tensile test, and the effects of crosslinking on the collagen structure of decellularized pericardium were determined by multiphoton microscopy. The viability of human umbilical vein endothelial cells seeded on decellularized human pericardium and on pericardium strongly and weakly crosslinked with glutaraldehyde and with genipin was evaluated by means of an MTS assay. The viability of the cells, measured by their metabolic activity, decreased considerably when the pericardium was crosslinked with glutaraldehyde. Conversely, the cell viability increased when the pericardium was crosslinked with genipin. Coating both non-modified pericardium and crosslinked pericardium with a fibrin mesh or with a mesh containing attached heparin and/or fibronectin led to a significant increase in cell viability. The highest degree of viability was attained for samples that were weakly crosslinked with genipin and modified by means of a fibrin and fibronectin coating. The results indicate a method by which in vivo endothelialization of human cardiac allografts or xenografts could potentially be encouraged.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":"15 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab52db","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41401164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-09DOI: 10.1088/1748-605X/ab4fb5
Chi-Yun Wang, Zong-Keng Kuo, M. Hsieh, L. Ke, Chihchen Chen, Chao-Min Cheng, P. Lai
Using three-dimensional (3D) bone engineering to fabricate bone segments is a better choice for repairing bone defects than using autologous bone. However, biomaterials for bone engineering are burdened with some clinical safety concerns. In this study, we layered commonly found clinical materials, hemostatic gelatin sponges, in a novel manner to create a 3D scaffold for bone engineering purposes. We further examined the comparable benefits of our design with both closed- and open-bottom holders. Cells in stacked layer disc systems were examined after a week of growth and differentiation. Osteoblasts in the outer layers of both closed- and open-bottom holder systems displayed gradually increased alkaline phosphatase (ALP) activity but decreased osteopontin (OPN) expression. Further, cell proliferation assays and LIVE/DEAD staining revealed decreased viable cell counts in the top layer with increased incubation time. However, while layered disc systems with closed-bottom holders underwent differentiation, they kept more differentiated cells alive within the gelatin sponge disc scaffold after 28 d of culturing. Whether cells were inoculated into the top, middle, or bottom portions of the layered disc stack, osteoblasts showed a preference for migrating to the top layer, in keeping with the oxygen and nutrients gradients. Regarding practical application, this study offers valuable information to promote the use of hemostatic gelatin sponges for bone engineering.
{"title":"Cell migration of preosteoblast cells on a clinical gelatin sponge for 3D bone tissue engineering","authors":"Chi-Yun Wang, Zong-Keng Kuo, M. Hsieh, L. Ke, Chihchen Chen, Chao-Min Cheng, P. Lai","doi":"10.1088/1748-605X/ab4fb5","DOIUrl":"https://doi.org/10.1088/1748-605X/ab4fb5","url":null,"abstract":"Using three-dimensional (3D) bone engineering to fabricate bone segments is a better choice for repairing bone defects than using autologous bone. However, biomaterials for bone engineering are burdened with some clinical safety concerns. In this study, we layered commonly found clinical materials, hemostatic gelatin sponges, in a novel manner to create a 3D scaffold for bone engineering purposes. We further examined the comparable benefits of our design with both closed- and open-bottom holders. Cells in stacked layer disc systems were examined after a week of growth and differentiation. Osteoblasts in the outer layers of both closed- and open-bottom holder systems displayed gradually increased alkaline phosphatase (ALP) activity but decreased osteopontin (OPN) expression. Further, cell proliferation assays and LIVE/DEAD staining revealed decreased viable cell counts in the top layer with increased incubation time. However, while layered disc systems with closed-bottom holders underwent differentiation, they kept more differentiated cells alive within the gelatin sponge disc scaffold after 28 d of culturing. Whether cells were inoculated into the top, middle, or bottom portions of the layered disc stack, osteoblasts showed a preference for migrating to the top layer, in keeping with the oxygen and nutrients gradients. Regarding practical application, this study offers valuable information to promote the use of hemostatic gelatin sponges for bone engineering.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab4fb5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47147103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-06DOI: 10.1088/1748-605X/ab5f9c
Eline-Claire Grosfeld, Brandon T. Smith, M. Santoro, Irene Lodoso-Torrecilla, J. Jansen, D. Ulrich, A. Melchiorri, David W Scott, A. Mikos, J. J. van den Beucken
Here, we demonstrate the in vivo efficacy of glucose microparticles (GMPs) to serve as porogens within calcium phosphate cements (CPCs) to obtain a fast-degrading bone substitute material. Composites were fabricated incorporating 20 wt% GMPs at two different GMP size ranges (100–150 μm (GMP-S) and 150–300 μm (GMP-L)), while CPC containing 20 wt% poly(lactic-co-glycolic acid) microparticles (PLGA) and plain CPC served as controls. After 2 and 8 weeks implantation in a rat femoral condyle defect model, specimens were retrieved and analyzed for material degradation and bone formation. Histologically, no adverse tissue response to any of the CPC-formulations was observed. All CPC-porogen formulations showed faster degradation compared to plain CPC control, but only GMP-containing formulations showed higher amounts of new bone formation compared to plain CPC controls. After 8 weeks, only CPC-porogen formulations with GMP-S or PLGA porogens showed higher degradation compared to plain CPC controls. Overall, the inclusion of GMPs into CPCs resulted in a macroporous structure that initially accelerated the generation of new bone. These findings highlight the efficacy of a novel approach that leverages simple porogen properties to generate porous CPCs with distinct degradation and bone regeneration profiles.
{"title":"Fast dissolving glucose porogens for early calcium phosphate cement degradation and bone regeneration","authors":"Eline-Claire Grosfeld, Brandon T. Smith, M. Santoro, Irene Lodoso-Torrecilla, J. Jansen, D. Ulrich, A. Melchiorri, David W Scott, A. Mikos, J. J. van den Beucken","doi":"10.1088/1748-605X/ab5f9c","DOIUrl":"https://doi.org/10.1088/1748-605X/ab5f9c","url":null,"abstract":"Here, we demonstrate the in vivo efficacy of glucose microparticles (GMPs) to serve as porogens within calcium phosphate cements (CPCs) to obtain a fast-degrading bone substitute material. Composites were fabricated incorporating 20 wt% GMPs at two different GMP size ranges (100–150 μm (GMP-S) and 150–300 μm (GMP-L)), while CPC containing 20 wt% poly(lactic-co-glycolic acid) microparticles (PLGA) and plain CPC served as controls. After 2 and 8 weeks implantation in a rat femoral condyle defect model, specimens were retrieved and analyzed for material degradation and bone formation. Histologically, no adverse tissue response to any of the CPC-formulations was observed. All CPC-porogen formulations showed faster degradation compared to plain CPC control, but only GMP-containing formulations showed higher amounts of new bone formation compared to plain CPC controls. After 8 weeks, only CPC-porogen formulations with GMP-S or PLGA porogens showed higher degradation compared to plain CPC controls. Overall, the inclusion of GMPs into CPCs resulted in a macroporous structure that initially accelerated the generation of new bone. These findings highlight the efficacy of a novel approach that leverages simple porogen properties to generate porous CPCs with distinct degradation and bone regeneration profiles.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab5f9c","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42812554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-05DOI: 10.1088/1748-605X/ab5f1a
G. Molino, M. Palmieri, Giorgia Montalbano, S. Fiorilli, C. Vitale-Brovarone
In the last decades, many research groups have experimented the synthesis of hydroxyapatite (HA) for bone tissue application obtaining products with different shapes and dimensions. This review aims to summarise and critically analyse the most used methods to prepare physiologic-like nano-HA, in the form of plates or rods, similar to the HA present in the human bones. Moreover, mesoporous HA has gained increasing interest in the biomedical field due its pecualiar structural features, such as high surface area and accessible mesoporous volume, which is known to confer enhanced biological behaviour and the possibility to act as nanocarriers of functional agents for bone-related therapies. For this reason, more recent studies related to the synthesis of mesoporous HA, with physiological-like morphology, are also considered in this review. Since a wide class of surfactant molecules plays an essential role both in the shape and size control of HA crystals and in the formation of mesoporosity, a section devoted to the mechanisms of action of several surfactants is also provided.
{"title":"Biomimetic and mesoporous nano-hydroxyapatite for bone tissue application: a short review","authors":"G. Molino, M. Palmieri, Giorgia Montalbano, S. Fiorilli, C. Vitale-Brovarone","doi":"10.1088/1748-605X/ab5f1a","DOIUrl":"https://doi.org/10.1088/1748-605X/ab5f1a","url":null,"abstract":"In the last decades, many research groups have experimented the synthesis of hydroxyapatite (HA) for bone tissue application obtaining products with different shapes and dimensions. This review aims to summarise and critically analyse the most used methods to prepare physiologic-like nano-HA, in the form of plates or rods, similar to the HA present in the human bones. Moreover, mesoporous HA has gained increasing interest in the biomedical field due its pecualiar structural features, such as high surface area and accessible mesoporous volume, which is known to confer enhanced biological behaviour and the possibility to act as nanocarriers of functional agents for bone-related therapies. For this reason, more recent studies related to the synthesis of mesoporous HA, with physiological-like morphology, are also considered in this review. Since a wide class of surfactant molecules plays an essential role both in the shape and size control of HA crystals and in the formation of mesoporosity, a section devoted to the mechanisms of action of several surfactants is also provided.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab5f1a","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45984589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-04DOI: 10.1088/1748-605X/ab5e52
H. Altinova, Sebastian Hammes, Moniek Palm, Pascal Achenbach, Jose L. Gerardo-Nava, R. Deumens, T. Führmann, S. V. van Neerven, E. Hermans, J. Weis, G. Brook
Severe spinal cord injury (SCI) results in permanent functional deficits, which despite pre-clinical advances, remain untreatable. Combinational approaches, including the implantation of bioengineered scaffolds are likely to promote significant tissue repair. However, this critically depends on the extent to which host tissue can integrate with the implant. In the present paper, blood vessel formation and maturation were studied within and around implanted micro-structured type-I collagen scaffolds at 10 weeks post implantation in adult rat mid-cervical spinal cord lateral funiculotomy injuries. Morphometric analysis revealed that blood vessel density within the scaffold was similar to that of the lateral white matter tracts that the implant replaced. However, immunohistochemistry for zonula occludens−1 (ZO-1) and endothelial barrier antigen revealed that scaffold microvessels remained largely immature, suggesting poor blood-spinal cord barrier (BSB) reformation. Furthermore, a band of intense ZO-1-immunoreactive fibroblast-like cells isolated the implant. Spinal cord vessels outside the ZO-1-band demonstrated BSB-formation, while vessels within the scaffold generally did not. The formation of a double-layered fibrotic and astroglial scar around the collagen scaffold might explain the relatively poor implant-host integration and suggests a mechanism for failed microvessel maturation. Targeted strategies that improve implant-host integration for such biomaterials will be vital for future tissue engineering and regenerative medicine approaches for traumatic SCI.
{"title":"Dense fibroadhesive scarring and poor blood vessel-maturation hamper the integration of implanted collagen scaffolds in an experimental model of spinal cord injury","authors":"H. Altinova, Sebastian Hammes, Moniek Palm, Pascal Achenbach, Jose L. Gerardo-Nava, R. Deumens, T. Führmann, S. V. van Neerven, E. Hermans, J. Weis, G. Brook","doi":"10.1088/1748-605X/ab5e52","DOIUrl":"https://doi.org/10.1088/1748-605X/ab5e52","url":null,"abstract":"Severe spinal cord injury (SCI) results in permanent functional deficits, which despite pre-clinical advances, remain untreatable. Combinational approaches, including the implantation of bioengineered scaffolds are likely to promote significant tissue repair. However, this critically depends on the extent to which host tissue can integrate with the implant. In the present paper, blood vessel formation and maturation were studied within and around implanted micro-structured type-I collagen scaffolds at 10 weeks post implantation in adult rat mid-cervical spinal cord lateral funiculotomy injuries. Morphometric analysis revealed that blood vessel density within the scaffold was similar to that of the lateral white matter tracts that the implant replaced. However, immunohistochemistry for zonula occludens−1 (ZO-1) and endothelial barrier antigen revealed that scaffold microvessels remained largely immature, suggesting poor blood-spinal cord barrier (BSB) reformation. Furthermore, a band of intense ZO-1-immunoreactive fibroblast-like cells isolated the implant. Spinal cord vessels outside the ZO-1-band demonstrated BSB-formation, while vessels within the scaffold generally did not. The formation of a double-layered fibrotic and astroglial scar around the collagen scaffold might explain the relatively poor implant-host integration and suggests a mechanism for failed microvessel maturation. Targeted strategies that improve implant-host integration for such biomaterials will be vital for future tissue engineering and regenerative medicine approaches for traumatic SCI.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab5e52","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45809985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-29DOI: 10.1088/1748-605X/ab5d7b
C. Wolf-Brandstetter, R. Beutner, R. Hess, S. Bierbaum, Katrin Wagner, D. Scharnweber, U. Gbureck, C. Moseke
For decades, the main focus of titanium implants developed to restore bone functionality was on improved osseointegration. Additional antimicrobial properties have now become desirable, due to the risk that rising antibiotic resistance poses for implant-associated infections. To this end, the trace elements of copper and zinc were integrated into calcium phosphate based coatings by electrochemically assisted deposition. In addition to their antimicrobial activity, zinc is reported to attract bone progenitor cells through chemotaxis and thus increase osteogenic differentiation, and copper to stimulate angiogenesis. Quantities of up to 68.9 ± 0.1 μg cm−2 of copper and 56.6 ± 0.4 μg cm−2 of zinc were deposited; co-deposition of both ions did not influence the amount of zinc but slightly increased the amount of copper in the coatings. The release of deposited copper and zinc species was negligible in serum-free simulated body fluid. In protein-containing solutions, a burst release of up to 10 μg ml−1 was observed for copper, while zinc was released continuously for up to 14 days. The presence of zinc was beneficial for adhesion and growth of human mesenchymal stromal cells in a concentration-dependent manner, but cytotoxic effects were already visible for coatings with an intermediate copper content. However, co-deposited zinc could somewhat alleviate the adverse effects of copper. Antimicrobial tests with E. coli revealed a decrease in adherent bacteria on brushite without copper or zinc of 60%, but if the coating contained both ions there was almost no bacterial adhesion after 12 h. Coatings with high zinc content and intermediate copper content had the overall best multifunctional properties.
{"title":"Multifunctional calcium phosphate based coatings on titanium implants with integrated trace elements","authors":"C. Wolf-Brandstetter, R. Beutner, R. Hess, S. Bierbaum, Katrin Wagner, D. Scharnweber, U. Gbureck, C. Moseke","doi":"10.1088/1748-605X/ab5d7b","DOIUrl":"https://doi.org/10.1088/1748-605X/ab5d7b","url":null,"abstract":"For decades, the main focus of titanium implants developed to restore bone functionality was on improved osseointegration. Additional antimicrobial properties have now become desirable, due to the risk that rising antibiotic resistance poses for implant-associated infections. To this end, the trace elements of copper and zinc were integrated into calcium phosphate based coatings by electrochemically assisted deposition. In addition to their antimicrobial activity, zinc is reported to attract bone progenitor cells through chemotaxis and thus increase osteogenic differentiation, and copper to stimulate angiogenesis. Quantities of up to 68.9 ± 0.1 μg cm−2 of copper and 56.6 ± 0.4 μg cm−2 of zinc were deposited; co-deposition of both ions did not influence the amount of zinc but slightly increased the amount of copper in the coatings. The release of deposited copper and zinc species was negligible in serum-free simulated body fluid. In protein-containing solutions, a burst release of up to 10 μg ml−1 was observed for copper, while zinc was released continuously for up to 14 days. The presence of zinc was beneficial for adhesion and growth of human mesenchymal stromal cells in a concentration-dependent manner, but cytotoxic effects were already visible for coatings with an intermediate copper content. However, co-deposited zinc could somewhat alleviate the adverse effects of copper. Antimicrobial tests with E. coli revealed a decrease in adherent bacteria on brushite without copper or zinc of 60%, but if the coating contained both ions there was almost no bacterial adhesion after 12 h. Coatings with high zinc content and intermediate copper content had the overall best multifunctional properties.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab5d7b","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41703467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-28DOI: 10.1088/1748-605X/ab5cfc
Ning Cui, Kai Han, M. Li, Jinlei Wang, Junmin Qian
Polypeptide-derived copolymers have widely been exploited for drug/gene delivery due to their pendant functional groups and non-toxic degradation products. However, fabrication of polypeptide-based scaffolds for tissue engineering has seldom been reported. In this study, foamy poly(Nε-benzyl formateoxycarbonyl-L-Lysine) (PZL) and poly(Nε-benzyl formateoxycarbonyl-L-lysine-co-L-phenylalanine) (PZLP) scaffolds were successfully prepared by a combination of ring-opening polymerization of α-amino acid N-carboxyanhydride and negative porous NaCl templating approach. The physicochemical properties of these scaffolds including glass transition temperature, contact angle, compression modulus and degradation behavior were characterized. Both in vitro and in vivo biocompatibility of the scaffolds were evaluated by MC3T3-E1 cell culture and SD subcutaneous model, respectively. The results from live-dead staining, MTT and ALP activity assays indicated that PZL scaffolds were more conducive to the adhesion, proliferation and osteoblastic differentiation of MC3T3-E1 cells compared to PZLP scaffolds in the initial culture period due to their specific surface properties. While porous structure rather than surface properties of scaffolds played a decisive role in the later stage of cell culture. The results of in vivo studies including H&E, Masson’s trichrome and CD34 staining further demonstrated that PZL scaffolds supported the ingrowth of microvessels than PZLP scaffolds due to their surface property difference. Collectively, PZL scaffolds displayed good biocompatibility and could be a promising candidate for tissue engineering application.
{"title":"Pure polylysine-based foamy scaffolds and their interaction with MC3T3-E1 cells and osteogenesis","authors":"Ning Cui, Kai Han, M. Li, Jinlei Wang, Junmin Qian","doi":"10.1088/1748-605X/ab5cfc","DOIUrl":"https://doi.org/10.1088/1748-605X/ab5cfc","url":null,"abstract":"Polypeptide-derived copolymers have widely been exploited for drug/gene delivery due to their pendant functional groups and non-toxic degradation products. However, fabrication of polypeptide-based scaffolds for tissue engineering has seldom been reported. In this study, foamy poly(Nε-benzyl formateoxycarbonyl-L-Lysine) (PZL) and poly(Nε-benzyl formateoxycarbonyl-L-lysine-co-L-phenylalanine) (PZLP) scaffolds were successfully prepared by a combination of ring-opening polymerization of α-amino acid N-carboxyanhydride and negative porous NaCl templating approach. The physicochemical properties of these scaffolds including glass transition temperature, contact angle, compression modulus and degradation behavior were characterized. Both in vitro and in vivo biocompatibility of the scaffolds were evaluated by MC3T3-E1 cell culture and SD subcutaneous model, respectively. The results from live-dead staining, MTT and ALP activity assays indicated that PZL scaffolds were more conducive to the adhesion, proliferation and osteoblastic differentiation of MC3T3-E1 cells compared to PZLP scaffolds in the initial culture period due to their specific surface properties. While porous structure rather than surface properties of scaffolds played a decisive role in the later stage of cell culture. The results of in vivo studies including H&E, Masson’s trichrome and CD34 staining further demonstrated that PZL scaffolds supported the ingrowth of microvessels than PZLP scaffolds due to their surface property difference. Collectively, PZL scaffolds displayed good biocompatibility and could be a promising candidate for tissue engineering application.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab5cfc","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41619804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alginate is one of the most favorable materials in many biomedical applications. The mechanical properties of alginate hydrogels can be easily tailored by adding different concentrations of divalent cations. In this work, we demonstrate that the method can also notably influence the biofouling behaviors of alginate hydrogels. A series of alginate hydrogels was prepared by tuning the concentrations of two types of divalent cation (Ca2+ or Ba2+). It was found that the biofouling behaviors of the hydrogels exhibited a ‘U’ curve tendency with the cation concentrations. Interestingly, we found that in optimal conditions ([Ca2+] = 0.9 mM or [Ba2+] = 0.54 mM), the resultant Ca0.9- and Ba0.54-alginate hydrogels were able to achieve negligible adhesion of the proteins and bacteria. Moreover, these two formulations were also able to prevent inflammatory responses at least 4 weeks after subcutaneous implantation in a mouse model. The findings in this work provide more insights into the design and development of appropriate alginate hydrogels for different applications.
{"title":"Influence of divalent cations on the biofouling behaviors of alginate hydrogels","authors":"Jiamin Zhang, Jia Ke, Yingnan Zhu, Jiayin Song, Jing Yang, Chiyu Wen, Lei Zhang","doi":"10.1088/1748-605X/ab4542","DOIUrl":"https://doi.org/10.1088/1748-605X/ab4542","url":null,"abstract":"Alginate is one of the most favorable materials in many biomedical applications. The mechanical properties of alginate hydrogels can be easily tailored by adding different concentrations of divalent cations. In this work, we demonstrate that the method can also notably influence the biofouling behaviors of alginate hydrogels. A series of alginate hydrogels was prepared by tuning the concentrations of two types of divalent cation (Ca2+ or Ba2+). It was found that the biofouling behaviors of the hydrogels exhibited a ‘U’ curve tendency with the cation concentrations. Interestingly, we found that in optimal conditions ([Ca2+] = 0.9 mM or [Ba2+] = 0.54 mM), the resultant Ca0.9- and Ba0.54-alginate hydrogels were able to achieve negligible adhesion of the proteins and bacteria. Moreover, these two formulations were also able to prevent inflammatory responses at least 4 weeks after subcutaneous implantation in a mouse model. The findings in this work provide more insights into the design and development of appropriate alginate hydrogels for different applications.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab4542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42633856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-20DOI: 10.1088/1748-605X/ab597f
Jing He, Zhenning Li, Tianhao Yu, Weizuo Wang, Meihan Tao, Shilin Wang, Yizhan Ma, Jun Fan, Xiaohong Tian, Xiaohong Wang, R. Javed, Q. Ao
This study addresses the fabrication of an extracellular matrix material of the acellular sheep periosteum and the systematic evaluation of its biocompatibility to explore its potential application in guided bone regeneration. Sheep periosteum was harvested and decellularized by a combined decellularization protocol. The effectiveness of cell removal was proved and residual α-Gal antigen was also quantitatively detected. Then, mouse MC3T3-E1 cells were seeded onto the acellular periosteum. A scanning electron microscope (SEM) was used to record the whole process of cell adhesion. The CCK-8 assay suggested that the acellular periosteum not only had zero toxic effect on pre-osteoblasts, but played a positive role in cell proliferation. We also tested whether the acellular periosteum possesses favorable osteogenesis induction activity using an alkaline phosphatase (ALP) assay and a quantitative real-time PCR (Col I, Runx2, OCN) assay. An in vivo study of a subcutaneous implantation test using Sprague Dawley (SD) rats was performed to detect the changes in IL-2, IFN-γ and IL-4 in serum and elucidate the host’s local response to acellular periosteum through hematoxylin and eosin (HE) and immunohistochemical staining. The results show that acellular sheep periosteum did not elicit a severe immunogenic response via the Th1 pathway, unlike fresh sheep periosteum. In conclusion, acellular sheep periosteum possesses favorable biocompatibility to be employed for guided bone regeneration.
本研究旨在制备脱细胞羊骨膜细胞外基质材料，并对其生物相容性进行系统评价，以探索其在引导骨再生中的潜在应用。采集羊骨膜，采用联合脱细胞方法进行脱细胞。证实了细胞去除的有效性，并定量检测了残留的α-Gal抗原。然后，将小鼠MC3T3-E1细胞接种到脱细胞骨膜上。用扫描电镜(SEM)记录了细胞粘附的全过程。CCK-8实验表明，脱细胞骨膜不仅对成骨前细胞无毒性作用，而且对细胞增殖有积极作用。我们还使用碱性磷酸酶(ALP)测定和实时荧光定量PCR (Col I, Runx2, OCN)测定测试了脱细胞骨膜是否具有良好的成骨诱导活性。采用SD (Sprague Dawley)大鼠皮下植入试验，通过苏木精伊红(HE)和免疫组化染色，检测血清中IL-2、IFN-γ和IL-4的变化，阐明宿主对脱细胞骨膜的局部反应。结果表明，与新鲜羊骨膜不同，脱细胞羊骨膜没有通过Th1途径引起严重的免疫原性反应。综上所述，脱细胞羊骨膜具有良好的生物相容性，可用于引导骨再生。
{"title":"In vitro and in vivo biocompatibility study on acellular sheep periosteum for guided bone regeneration","authors":"Jing He, Zhenning Li, Tianhao Yu, Weizuo Wang, Meihan Tao, Shilin Wang, Yizhan Ma, Jun Fan, Xiaohong Tian, Xiaohong Wang, R. Javed, Q. Ao","doi":"10.1088/1748-605X/ab597f","DOIUrl":"https://doi.org/10.1088/1748-605X/ab597f","url":null,"abstract":"This study addresses the fabrication of an extracellular matrix material of the acellular sheep periosteum and the systematic evaluation of its biocompatibility to explore its potential application in guided bone regeneration. Sheep periosteum was harvested and decellularized by a combined decellularization protocol. The effectiveness of cell removal was proved and residual α-Gal antigen was also quantitatively detected. Then, mouse MC3T3-E1 cells were seeded onto the acellular periosteum. A scanning electron microscope (SEM) was used to record the whole process of cell adhesion. The CCK-8 assay suggested that the acellular periosteum not only had zero toxic effect on pre-osteoblasts, but played a positive role in cell proliferation. We also tested whether the acellular periosteum possesses favorable osteogenesis induction activity using an alkaline phosphatase (ALP) assay and a quantitative real-time PCR (Col I, Runx2, OCN) assay. An in vivo study of a subcutaneous implantation test using Sprague Dawley (SD) rats was performed to detect the changes in IL-2, IFN-γ and IL-4 in serum and elucidate the host’s local response to acellular periosteum through hematoxylin and eosin (HE) and immunohistochemical staining. The results show that acellular sheep periosteum did not elicit a severe immunogenic response via the Th1 pathway, unlike fresh sheep periosteum. In conclusion, acellular sheep periosteum possesses favorable biocompatibility to be employed for guided bone regeneration.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab597f","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43734328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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