Pub Date : 2020-02-17DOI: 10.1088/1748-605X/ab5e1b
Jakob M Townsend, Makenna E Hukill, Kar-Ming Fung, Devan G Ohst, Jed K Johnson, Robert A Weatherly, Michael S Detamore
Difficulty breathing due to tracheal stenosis (i.e. narrowed airway) diminishes the quality of life and can potentially be life-threatening. Tracheal stenosis can be caused by congenital anomalies, external trauma, infection, intubation-related injury, and tumors. Common treatment methods for tracheal stenosis requiring surgical intervention include end-to-end anastomosis, slide tracheoplasty and/or laryngotracheal reconstruction. Although the current methods have demonstrated promise for treatment of tracheal stenosis, a clear need exists for the development of new biomaterials that can hold the trachea open after the stenosed region has been surgically opened, and that can support healing without the need to harvest autologous tissue from the patient. The current study therefore evaluated the use of electrospun nanofiber scaffolds encapsulating 3D-printed PCL rings to patch induced defects in rabbit tracheas. The nanofibers were a blend of polycaprolactone (PCL) and polylactide-co-caprolactone (PLCL), and encapsulated either the cell adhesion peptide, RGD, or antimicrobial compound, ceragenin-131 (CSA). Blank PCL/PLCL and PCL were employed as control groups. Electrospun patches were evaluated in a rabbit tracheal defect model for 12 weeks, which demonstrated re-epithelialization of the luminal side of the defect. No significant difference in lumen volume was observed for the PCL/PLCL patches compared to the uninjured positive control. Only the RGD group did not lead to a significant decrease in the minimum cross-sectional area compared to the uninjured positive control. CSA reduced bacteria growth in vitro, but did not add clear value in vivo. Adequate tissue in-growth into the patches and minimal tissue overgrowth was observed inside the patch material. Areas of future investigation include tuning the material degradation time to balance cell adhesion and structural integrity.
{"title":"Biodegradable electrospun patch containing cell adhesion or antimicrobial compounds for trachea repair in vivo.","authors":"Jakob M Townsend, Makenna E Hukill, Kar-Ming Fung, Devan G Ohst, Jed K Johnson, Robert A Weatherly, Michael S Detamore","doi":"10.1088/1748-605X/ab5e1b","DOIUrl":"10.1088/1748-605X/ab5e1b","url":null,"abstract":"<p><p>Difficulty breathing due to tracheal stenosis (i.e. narrowed airway) diminishes the quality of life and can potentially be life-threatening. Tracheal stenosis can be caused by congenital anomalies, external trauma, infection, intubation-related injury, and tumors. Common treatment methods for tracheal stenosis requiring surgical intervention include end-to-end anastomosis, slide tracheoplasty and/or laryngotracheal reconstruction. Although the current methods have demonstrated promise for treatment of tracheal stenosis, a clear need exists for the development of new biomaterials that can hold the trachea open after the stenosed region has been surgically opened, and that can support healing without the need to harvest autologous tissue from the patient. The current study therefore evaluated the use of electrospun nanofiber scaffolds encapsulating 3D-printed PCL rings to patch induced defects in rabbit tracheas. The nanofibers were a blend of polycaprolactone (PCL) and polylactide-co-caprolactone (PLCL), and encapsulated either the cell adhesion peptide, RGD, or antimicrobial compound, ceragenin-131 (CSA). Blank PCL/PLCL and PCL were employed as control groups. Electrospun patches were evaluated in a rabbit tracheal defect model for 12 weeks, which demonstrated re-epithelialization of the luminal side of the defect. No significant difference in lumen volume was observed for the PCL/PLCL patches compared to the uninjured positive control. Only the RGD group did not lead to a significant decrease in the minimum cross-sectional area compared to the uninjured positive control. CSA reduced bacteria growth in vitro, but did not add clear value in vivo. Adequate tissue in-growth into the patches and minimal tissue overgrowth was observed inside the patch material. Areas of future investigation include tuning the material degradation time to balance cell adhesion and structural integrity.</p>","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2020-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49667348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Because the collagen membrane lacks osteoinductivity, it must be modified with bioactive components to trigger rapid bone regeneration. In this study, we aimed to evaluate the bone regeneration effects of a collagen membrane chemically conjugated with stromal cell-derived factor-1 alpha (SDF-1α) in rat models. To this end, different collagen membranes from four groups including a control group with a Bio-Oss bone substitute + collagen membrane; physical adsorption group with Bio-Oss + SDF-1α physically adsorbed on the collagen membrane; chemical cross-linking group with Bio-Oss + SDF-1α chemically cross-linked to the collagen membrane; and cell-seeding group with Bio-Oss + bone marrow mesenchymal stem cells (BMSCs) seeded onto the collagen membrane were placed in critical-sized defect models using a guided bone regeneration technique. At 4 and 8 weeks, the specimens were analyzed by scanning electron microscopy, energy-dispersive x-ray spectroscopy, micro-computed tomography, and histomorphology analyzes. Furthermore, ectopic osteogenesis was examined by histological analysis with Von Kossa staining, with the samples counterstained by hematoxylin and eosin and immunohistochemical staining. The results showed that in the chemical cross-linking group and cell-seeding group, the bone volume fraction, bone surface area fraction, and trabecular number were significantly increased and showed more new bone formation compared to the control and physical adsorption groups. Von Kossa-stained samples counterstained with hematoxylin and eosin and subjected to immunohistochemical staining of 4-week implanted membranes revealed that the chemical cross-linking group had the largest number of microvessels. The collagen membrane chemically conjugated with SDF-1α to significantly promote new bone and microvessel formation compared to SDF-1α physical adsorption and showed similar effects on new bone formation as a BMSC seeding method. This study provided a cell-free approach for shortening the bone healing time and improving the success rate of guided bone regeneration.
{"title":"Evaluation of bone-regeneration effects and ectopic osteogenesis of collagen membrane chemically conjugated with stromal cell-derived factor-1 in vivo","authors":"Xiaolin Yu, Haipeng Sun, Jiamin Yang, Yun Liu, Zhengchuan Zhang, Jinming Wang, Feilong Deng","doi":"10.1088/1748-605X/ab52da","DOIUrl":"https://doi.org/10.1088/1748-605X/ab52da","url":null,"abstract":"Because the collagen membrane lacks osteoinductivity, it must be modified with bioactive components to trigger rapid bone regeneration. In this study, we aimed to evaluate the bone regeneration effects of a collagen membrane chemically conjugated with stromal cell-derived factor-1 alpha (SDF-1α) in rat models. To this end, different collagen membranes from four groups including a control group with a Bio-Oss bone substitute + collagen membrane; physical adsorption group with Bio-Oss + SDF-1α physically adsorbed on the collagen membrane; chemical cross-linking group with Bio-Oss + SDF-1α chemically cross-linked to the collagen membrane; and cell-seeding group with Bio-Oss + bone marrow mesenchymal stem cells (BMSCs) seeded onto the collagen membrane were placed in critical-sized defect models using a guided bone regeneration technique. At 4 and 8 weeks, the specimens were analyzed by scanning electron microscopy, energy-dispersive x-ray spectroscopy, micro-computed tomography, and histomorphology analyzes. Furthermore, ectopic osteogenesis was examined by histological analysis with Von Kossa staining, with the samples counterstained by hematoxylin and eosin and immunohistochemical staining. The results showed that in the chemical cross-linking group and cell-seeding group, the bone volume fraction, bone surface area fraction, and trabecular number were significantly increased and showed more new bone formation compared to the control and physical adsorption groups. Von Kossa-stained samples counterstained with hematoxylin and eosin and subjected to immunohistochemical staining of 4-week implanted membranes revealed that the chemical cross-linking group had the largest number of microvessels. The collagen membrane chemically conjugated with SDF-1α to significantly promote new bone and microvessel formation compared to SDF-1α physical adsorption and showed similar effects on new bone formation as a BMSC seeding method. This study provided a cell-free approach for shortening the bone healing time and improving the success rate of guided bone regeneration.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2019-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab52da","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48814622","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/ab52e2
S. Jana, F. Franchi, A. Lerman
A tissue-engineered heart valve can be an alternative to current mechanical or bioprosthetic valves that face limitations, especially in pediatric patients. However, it remains challenging to produce a functional tissue-engineered heart valve with three leaflets mimicking the trilayered, oriented structure of a native valve leaflet. In our previous study, a flat, trilayered nanofibrous substrate mimicking the orientations of three layers in a native leaflet—circumferential, random and radial orientations in fibrosa, spongiosa and ventricularis layers, respectively, was developed through electrospinning. In this study, we sought to develop a trilayered tissue structure mimicking the orientations of a native valve leaflet through in vivo tissue engineering, a practical regenerative medicine technology that can be used to develop an autologous heart valve. Thus, the nanofibrous substrate was placed inside the closed trileaflet-shaped cavity of a mold and implanted subcutaneously in a rat model for in vivo tissue engineering. After two months, the explanted tissue construct had a trilayered structure mimicking the orientations of a native valve leaflet. The infiltrated cells and their deposited collagen fibrils were oriented along the nanofibers in each layer of the substrate. Besides collagen, presence of glycosaminoglycans and elastin in the construct was observed.
{"title":"Trilayered tissue structure with leaflet-like orientations developed through in vivo tissue engineering","authors":"S. Jana, F. Franchi, A. Lerman","doi":"10.1088/1748-605X/ab52e2","DOIUrl":"https://doi.org/10.1088/1748-605X/ab52e2","url":null,"abstract":"A tissue-engineered heart valve can be an alternative to current mechanical or bioprosthetic valves that face limitations, especially in pediatric patients. However, it remains challenging to produce a functional tissue-engineered heart valve with three leaflets mimicking the trilayered, oriented structure of a native valve leaflet. In our previous study, a flat, trilayered nanofibrous substrate mimicking the orientations of three layers in a native leaflet—circumferential, random and radial orientations in fibrosa, spongiosa and ventricularis layers, respectively, was developed through electrospinning. In this study, we sought to develop a trilayered tissue structure mimicking the orientations of a native valve leaflet through in vivo tissue engineering, a practical regenerative medicine technology that can be used to develop an autologous heart valve. Thus, the nanofibrous substrate was placed inside the closed trileaflet-shaped cavity of a mold and implanted subcutaneously in a rat model for in vivo tissue engineering. After two months, the explanted tissue construct had a trilayered structure mimicking the orientations of a native valve leaflet. The infiltrated cells and their deposited collagen fibrils were oriented along the nanofibers in each layer of the substrate. Besides collagen, presence of glycosaminoglycans and elastin in the construct was observed.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2019-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab52e2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42088339","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/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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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.
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