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Paulo G. Coelho - One of the best experts on this subject based on the ideXlab platform.
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Repair of Critical-Sized Long Bone Defects Using Dipyridamole-Augmented 3D-Printed Bioactive Ceramic Scaffolds.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2019Co-Authors: Lukasz Witek, Christopher D. Lopez, Bruce N. Cronstein, Eduardo D. Rodriguez, Adham M. Alifarag, Nick Tovar, Paulo G. CoelhoAbstract:There are over two million long bone defects treated in the United States annually, of which ~5% will not heal without significant surgical intervention. While autogenous grafting is the standard of care in simple defects, a customized scaffold for large defects in unlimited quantities is not available. Recently, a three-dimensionally (3D)-printed Bioactive Ceramic (3DPBC) scaffold has been successfully utilized in the of repair critical-sized (CSD) long bone defects in vivo. In this study, 3DPBC scaffolds were augmented with dipyridamole (DIPY), an adenosine A2A receptor (A2A R) indirect agonist, because of its known effect to enhance bone formation. CSD full thickness segmental defects (~11 mm × full thickness) defects were created in the radial diaphysis in New Zealand white rabbits (n = 24). A customized 3DPBC scaffold composed of β-tricalcium phosphate was placed into the defect site. Groups included scaffolds that were collagen-coated (COLL), or immersed in 10, 100, or 1,000 μM DIPY solution. Animals were euthanized 8 weeks post-operatively and the radii/ulna-scaffold complex retrieved en bloc, for micro-CT, histological, and mechanical analysis. Bone growth was assessed exclusively within scaffold pores and evaluated by microCT and advanced reconstruction software. Biomechanical properties were evaluated utilizing nanoindentation to assess the newly regenerated bone for elastic modulus (E) and hardness (H). MicroCT reconstructions illustrated bone in-growth throughout the scaffold, with an increase in bone volume dependent on the DIPY dosage. The histological evaluation did not indicate any adverse immune response while revealing progressive remodeling of bone. These customized biologic 3DPBC scaffolds have the potential of repairing and regenerating bone. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2499-2507, 2019.
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Dipyridamole Augments Three-Dimensionally Printed Bioactive Ceramic Scaffolds to Regenerate Craniofacial Bone.
Plastic and reconstructive surgery, 2019Co-Authors: Christopher D. Lopez, J. Rodrigo Diaz-siso, Lukasz Witek, Jonathan M. Bekisz, Luiz Fernando Gil, Bruce N. Cronstein, Roberto L. Flores, Andrea Torroni, Eduardo D. Rodriguez, Paulo G. CoelhoAbstract:BACKGROUND Autologous bone grafts remain a standard of care for the reconstruction of large bony defects, but limitations persist. The authors explored the bone regenerative capacity of customized, three-dimensionally printed Bioactive Ceramic scaffolds with dipyridamole, an adenosine A2A receptor indirect agonist known to enhance bone formation. METHODS Critical-size bony defects (10-mm height, 10-mm length, full-thickness) were created at the mandibular rami of rabbits (n = 15). Defects were replaced by a custom-to-defect, three-dimensionally printed Bioactive Ceramic scaffold composed of β-tricalcium phosphate. Scaffolds were uncoated (control), collagen-coated, or immersed in 100 μM dipyridamole. At 8 weeks, animals were euthanized and the rami retrieved. Bone growth was assessed exclusively within scaffold pores, and evaluated by micro-computed tomography/advanced reconstruction software. Micro-computed tomographic quantification was calculated. Nondecalcified histology was performed. A general linear mixed model was performed to compare group means and 95 percent confidence intervals. RESULTS Qualitative analysis did not show an inflammatory response. The control and collagen groups (12.3 ± 8.3 percent and 6.9 ± 8.3 percent bone occupancy of free space, respectively) had less bone growth, whereas the most bone growth was in the dipyridamole group (26.9 ± 10.7 percent); the difference was statistically significant (dipyridamole versus control, p < 0.03; dipyridamole versus collagen, p < 0.01 ). There was significantly more residual scaffold material for the collagen group relative to the dipyridamole group (p < 0.015), whereas the control group presented intermediate values (nonsignificant relative to both collagen and dipyridamole). Highly cellular and vascularized intramembranous-like bone healing was observed in all groups. CONCLUSION Dipyridamole significantly increased the three-dimensionally printed Bioactive Ceramic scaffold's ability to regenerate bone in a thin bone defect environment.
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three dimensionally printed Bioactive Ceramic scaffold osseoconduction across critical sized mandibular defects
Journal of Surgical Research, 2018Co-Authors: Christopher D. Lopez, Lukasz Witek, Jonathan M. Bekisz, Bruce N. Cronstein, Roberto L. Flores, Andrea Torroni, Eduardo D. Rodriguez, Rodrigo J Diazsiso, Paulo G. CoelhoAbstract:Abstract Background Vascularized bone tissue transfer, commonly used to reconstruct large mandibular defects, is challenged by long operative times, extended hospital stay, donor-site morbidity, and resulting health care. 3D-printed osseoconductive tissue-engineered scaffolds may provide an alternative solution for reconstruction of significant mandibular defects. This pilot study presents a novel 3D-printed Bioactive Ceramic scaffold with osseoconductive properties to treat segmental mandibular defects in a rabbit model. Methods Full-thickness mandibulectomy defects (12 mm) were created at the mandibular body of eight adult rabbits and replaced by 3D-printed Ceramic scaffold made of 100% β-tricalcium phosphate, fit to defect based on computed tomography imaging. After 8 weeks, animals were euthanized, the mandibles were retrieved, and bone regeneration was assessed. Bone growth was qualitatively assessed with histology and backscatter scanning electron microscopy, quantified both histologically and with micro computed tomography and advanced 3D image reconstruction software, and compared to unoperated mandible sections (UMSs). Results Histology quantified scaffold with newly formed bone area occupancy at 54.3 ± 11.7%, compared to UMS baseline bone area occupancy at 55.8 ± 4.4%, and bone area occupancy as a function of scaffold free space at 52.8 ± 13.9%. 3D volume occupancy quantified newly formed bone volume occupancy was 36.3 ± 5.9%, compared to UMS baseline bone volume occupancy at 33.4 ± 3.8%, and bone volume occupancy as a function of scaffold free space at 38.0 ± 15.4%. Conclusions 3D-printed Bioactive Ceramic scaffolds can restore critical mandibular segmental defects to levels similar to native bone after 8 weeks in an adult rabbit, critical sized, mandibular defect model.
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Dipyridamole enhances osteogenesis of three-dimensionally printed Bioactive Ceramic scaffolds in calvarial defects.
Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery, 2017Co-Authors: Jonathan M. Bekisz, Christopher D. Lopez, Lukasz Witek, Bruce N. Cronstein, Roberto L. Flores, Andrea Torroni, Christopher M. Runyan, Paulo G. CoelhoAbstract:Abstract Purpose The objective of this study was to test the osteogenic capacity of dipyridamole-loaded, three-dimensionally printed, Bioactive Ceramic (3DPBC) scaffolds using a translational, skeletally mature, large-animal calvarial defect model. Materials and methods Custom 3DPBC scaffolds designed to present lattice-based porosity only towards the dural surface were either coated with collagen (control) or coated with collagen and immersed in a 100 μM concentration dipyridamole (DIPY) solution. Sheep (n = 5) were subjected to 2 ipsilateral trephine-induced (11-mm diameter) calvarial defects. Either a control or a DIPY scaffold was placed in each defect, and the surgery was repeated on the contralateral side 3 weeks later. Following sacrifice, defects were evaluated through microcomputed tomography and histologic analysis for bone, scaffold, and soft tissue quantification throughout the defect. Parametric and non-parametric methods were used to determine statistical significance based on data distribution. Results No exuberant or ectopic bone formation was observed, and no histologic evidence of inflammation was noted within the defects. Osteogenesis was higher in DIPY-coated scaffolds compared to controls at 3 weeks (p = 0.013) and 6 weeks (p = 0.046) in vivo. When bone formation was evaluated as a function of defect radius, average bone formation was higher for DIPY relative to control scaffolds at both time points (significant at defect central regions at 3 weeks and at margins at 6 weeks, p = 0.046 and p = 0.031, respectively). Conclusion Dipyridamole significantly improves the calvarial bone regeneration capacity of 3DPBC scaffolds. The most significant difference in bone regeneration was observed centrally within the interface between the 3DPBC scaffold and the dura mater.
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thin Bioactive Ceramic coated alumina blasted acid etched implant surface enhances biomechanical fixation of implants an experimental study in dogs
Clinical Implant Dentistry and Related Research, 2011Co-Authors: Rodrigo Granato, Charles Marin, Jose Nazareno Gil, Sung Kiang Chuang, Thomas B Dodson, Marcelo Suzuki, Paulo G. CoelhoAbstract:Background: Thin bioCeramic coatings have been regarded as potential substitutes for plasma-sprayed hydroxyapatite coatings. Purpose: This study tested the hypothesis that a thin Bioactive Ceramic coating deposition on an alumina-blasted/acid-etched (AB/AE) surface would positively affect the biomechanical fixation and bone-to-implant contact (BIC) of plateau root form implants. Materials and Methods: Implants of two different lengths (i.e., 4.5 × 11 mm long, n = 36) and 4.5 × 6 mm (short, n = 36) and two different surfaces, that is, control (AB/AE) and test (AB/AE + 300 – 500 nm Bioactive Ceramic coating), were placed in the proximal tibiae of six beagle dogs. The implants were retrieved for analyses 2 and 4 weeks after placement. The implants in bone specimens were subjected to torque loads until a 10% drop of the maximum torque was recorded. The specimens were evaluated under optical microscopy for bone morphology and percent BIC. Statistical analysis was performed by a generalized linear mixed effects analysis of variance model and statistical significance set at p < 0.05. Results: Significantly higher torque-to-interface fracture levels for test surface groups of both lengths when compared to control surfaces were observed. No significant difference in BIC was observed between test and control implants of equal length. Histomorphological analysis showed higher degrees of bone organization between the plateaus of test implant surfaces at both implantation times. Conclusion: Because the presence of a thin Bioactive Ceramic coating on the surface did not affect BIC, but positively affected implant biomechanical fixation, the hypothesis was partially validated.
Hala Zreiqat - One of the best experts on this subject based on the ideXlab platform.
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silk coating on a Bioactive Ceramic scaffold for bone regeneration effective enhancement of mechanical and in vitro osteogenic properties towards load bearing applications
Journal of Tissue Engineering and Regenerative Medicine, 2017Co-Authors: Jiao Jiao Li, Seyediman Roohaniesfahani, David L Kaplan, Hala ZreiqatAbstract:Bioactive Ceramic scaffolds represent competitive choices for clinical bone reconstruction, but their widespread use is restricted by inherent brittleness and weak mechanical performance under load. This study reports the development of strong and tough Bioactive scaffolds suitable for use in load-bearing bone reconstruction. A strong and Bioactive Ceramic scaffold (strontium-hardystonite-gahnite) is combined with single and multiple coating layers of silk fibroin to enhance its toughness, producing composite scaffolds which match the mechanical properties of cancellous bone and show enhanced capacity to promote in vitro osteogenesis. Also reported for the first time is a comparison of the coating effects obtained when a polymeric material is coated on Ceramic scaffolds with differing microstructures, namely the strontium-hardystonite-gahnite scaffold with high-density struts as opposed to a conventional Ceramic scaffold, such as biphasic calcium phosphate, with low-density struts. The results show that silk coating on a unique Ceramic scaffold can lead to simple and effective enhancement of its mechanical and biological properties to suit a wider range of applications in clinical bone reconstruction, and also establish the influence of Ceramic microstructure on the effectiveness of silk coating as a method of reinforcement when applied to different types of Ceramic bone graft substitutes. Copyright © 2015 John Wiley & Sons, Ltd.
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a biphasic scaffold based on silk and Bioactive Ceramic with stratified properties for osteochondral tissue regeneration
Journal of Materials Chemistry B, 2015Co-Authors: Jiao Jiao Li, Seyediman Roohaniesfahani, David L Kaplan, Hala ZreiqatAbstract:Significant clinical challenges encountered in the effective long-term treatment of osteochondral defects have inspired advancements in scaffold-based tissue engineering techniques to aid repair and regeneration. This study reports the development of a biphasic scaffold produced via a rational combination of silk fibroin and Bioactive Ceramic with stratified properties to satisfy the complex and diverse regenerative requirements of osteochondral tissue. Structural examination showed that the biphasic scaffold contained two phases with different pore morphologies to match the cartilage and bone segments of osteochondral tissue, which were joined at a continuous interface. Mechanical assessment showed that the two phases of the biphasic scaffold imitated the load-bearing behaviour of native osteochondral tissue and matched its compressive properties. In vitro testing showed that different compositions in the two phases of the biphasic scaffold could direct the preferential differentiation of human mesenchymal stem cells towards the chondrogenic or osteogenic lineage. By featuring simple and reproducible fabrication and a well-integrated interface, the biphasic scaffold strategy established in this study circumvented the common problems experienced with integrated scaffold designs and could provide an effective approach for the regeneration of osteochondral tissue.
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Fabrication of a novel triphasic and Bioactive Ceramic and evaluation of its in vitro and in vivo cytocompatibility and osteogenesis.
Journal of materials chemistry. B, 2014Co-Authors: Seyed-iman Roohani-esfahani, Kai Yuen Wong, Yongjuan Chen, Stan Gronthos, Danijela Menicanin, Jeffrey Shi, Colin R. Dunstan, Hala ZreiqatAbstract:We report, for the first time, the synthesis of a novel triphasic and crystalline Bioactive Ceramic (MSM-10) with the ability to simultaneously release three types of Bioactive ions (strontium (Sr), silicon (Si) and magnesium (Mg)) to the surrounding microenvironment. An MSM-10 powder with a nominal composition (wt%) of 54 Mg2SiO4, 36 Si3Sr5 and 10 MgO was prepared by the sol–gel method and fabricated as porous scaffolds using the foam replication method. The effects of the different amounts of the phases in the Ceramics on the mechanical and physical properties of the scaffolds as well as their in vitro and in vivo behaviors were comprehensively investigated. Biphasic calcium phosphate (BCP, β-tricalcium phosphate (60 wt%)/hydroxyapatite (40 wt%)) scaffolds were used as the control material. The attachment, morphology, proliferation and differentiation of primary human osteoblasts (HOBs) were investigated after cell culturing on the various scaffolds. In vitro cytotoxicity (ISO/EN 10993-5) results not only indicated the biocompatibility of MSM-10, but also its positive effects on inducing the proliferation of HOBs. Our results showed significant enhancement in osteogenic gene expression levels (Runx2, osteocalcin, osteopontin and bone sialoprotein), when HOBs were cultured on MSM-10, compared to those for BCP and other generated Ceramic scaffolds. For the in vivo studies, the different types of the materials were seeded with cultured human mesenchymal stem cells (hMSC) and then subcutaneously transplanted into the dorsal surface of eight-week-old immunocompromised (NOD/SCID) mice. MSM-10 demonstrated a significant amount of new bone formation compared to the other groups tested with no macroscopic signs of inflammation or toxicity in the tissue surrounding the implants. The novel MSM-10 Ceramic presents promising potential for bone regeneration in orthopaedic and maxillofacial applications.
Ahmed El-ghannam - One of the best experts on this subject based on the ideXlab platform.
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Acceleration of Alveolar Ridge Augmentation Using a Low Dose of Recombinant Human Bone Morphogenetic Protein-2 Loaded on a Resorbable Bioactive Ceramic
Journal of Oral and Maxillofacial Surgery, 2015Co-Authors: Ragia A. Fahmy, Naguiba Mahmoud, Samia Soliman, Larry Cunningham, Samir R. Nouh, Ahmed El-ghannamAbstract:Purpose The aim of the present study was to evaluate the effect of a porous silica-calcium phosphate composite (SCPC50) loaded with and without recombinant human bone morphogenetic protein-2 (rhBMP-2) on alveolar ridge augmentation in saddle-type defects. Materials and Methods Micro-granules of SCPC50 resorbable Bioactive Ceramic were coated with rhBMP-2 10 mg and then implanted into a saddle-type defect (12 × 7 mm) in a dog mandible and covered with a collagen membrane. Control groups included defects grafted with SCPC50 granules without rhBMP-2 and un-grafted defects. Bone healing was evaluated at 8 and 16 weeks using histologic and histomorphometric techniques. The increase in bone height and total defect fill were assessed for each specimen using the ImageJ 1.46 program. The release kinetics of rhBMP-2 was determined in vitro. The height of the bone in the grafted defects and the total defect fill were statistically analyzed. Results SCPC50 enhanced alveolar ridge augmentation as indicated by the increased vertical bone height, bone surface area, and bone volume after 16 weeks. SCPC50-rhBMP-2 provided a sustained release profile of a low effective dose (BMP-2 4.6 ± 1.34 pg/mL per hour) during the 1- to 21-day period. The slow rate of release of rhBMP-2 from SCPC50 accelerated synchronized complete bone regeneration and graft material resorption in 8 weeks. Successful rapid reconstruction of the alveolar ridge by SCPC50 and SCPC50-rhBMP-2 occurred without any adverse excessive bone formation, inflammation, or fluid-filled voids. Conclusions Results of this study suggest that SCPC50 is an effective graft material to preserve the alveolar ridge after tooth extraction. Coating SCPC50-rhBMP-2 further accelerated bone regeneration and a considerable increase in vertical bone height. These findings make SCPC50 the primary choice as a carrier for rhBMP-2. SCPC50-rhBMP-2 can serve as an alternative to autologous bone grafting.
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Early osteoblast responses to orthopedic implants: Synergy of surface roughness and chemistry of Bioactive Ceramic coating
Journal of biomedical materials research. Part A, 2014Co-Authors: Aniket, Robert W. Reid, Benika Hall, Ian Marriott, Ahmed El-ghannamAbstract:Pro-osteogenic stimulation of bone cells by Bioactive Ceramic-coated orthopedic implants is influenced by both surface roughness and material chemistry; however, their concomitant impact on osteoblast behavior is not well understood. The aim of this study is to investigate the effects of nano-scale roughness and chemistry of Bioactive silica-calcium phosphate nanocomposite (SCPC50) coated Ti-6Al-4V on modulating early bone cell responses. Cell attachment was higher on SCPC50-coated substrates compared to the uncoated controls; however, cells on the uncoated substrate exhibited greater spreading and superior quality of F-actin filaments than cells on the SCPC50-coated substrates. The poor F-actin filament organization on SCPC50-coated substrates is thought to be due to the enhanced calcium uptake by the Ceramic surface. Dissolution analyses showed that an increase in surface roughness was accompanied by increased calcium uptake, and increased phosphorous and silicon release, all of which appear to interfere with F-actin assembly and osteoblast morphology. Moreover, cell attachment onto the SCPC50-coated substrates correlated with the known adsorption of fibronectin, and was independent of surface roughness. High-throughput genome sequencing showed enhanced expression of extracellular matrix and cell differentiation related genes. These results demonstrate a synergistic relationship between Bioactive Ceramic coating roughness and material chemistry resulting in a phenotype that leads to early osteoblast differentiation. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1961–1973, 2015.
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Promotion of pro-osteogenic responses by a Bioactive Ceramic coating
Journal of biomedical materials research. Part A, 2012Co-Authors: Aniket, Ian Marriott, Amy B. Young, Ahmed El-ghannamAbstract:The objective of this study was to analyze the responses of bone-forming osteoblasts to Ti-6Al-4V implant material coated with silica-calcium phosphate nanocomposite (SCPC50). Osteoblast differentiation at the interface with SCPC50-coated Ti-6Al-4V was correlated to the adsorption of high amount of serum proteins, high surface affinity to fibro- nectin, Ca uptake from and P and Si release into the medium. SCPC50-coated Ti-6Al-4V adsorbed significantly more serum protein (p < 0.05) than control uncoated substrates. Moreover, Western blot analysis showed that the SCPC50 coating had a high affinity for serum fibronectin. Protein conformation anal- yses by FTIR showed that the ratio of the area under the peak for amide I/amide II bands was significantly higher (p < 0.05) on the surface of SCPC50-coated substrates than that on the surface of the control uncoated substrates. Moreover, ICP � OES analyses indicated that SCPC50-coated substrates with- drew Ca ions from, and released P and Si ions into, the tissue culture medium, respectively. In conjunction with the favor- able protein adsorption and modifications in medium compo- sition, MC3T3-E1 osteoblast-like cells attached to SCPC50- coated substrates expressed 10-fold higher level of mRNA encoding osteocalcin and had significantly higher production of osteopontin and osteocalcin proteins than cells attached to the uncoated Ti-6A1-4V substrates. In addition, osteoblast-like cells attached to the SCPC50-coated substrates produced significantly lower levels of the inflammatory and osteoclasto- genic cytokines, IL-6, IL-12p40, and RANKL than those attached to uncoated Ti-6Al-4V substrates. These results sug- gest that SCPC50 coating could enhance bone integration with orthopedic and maxillofacial implants while minimizing the induction of inflammatory bone cell responses. V C 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 3314-3325, 2012.
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Resorbable Bioactive Ceramic for treatment of bone infection.
Journal of biomedical materials research. Part A, 2010Co-Authors: Ahmed El-ghannam, Kiarash Jahed, Meera GovindaswamiAbstract:Polymethylmethacrylate (PMMA) beads have been widely used in the treatment of bone infection over the last three decades. Although PMMA does offer a mechanism to quickly and effectively administer a localized dose of antibiotic to the site of infection, its efficacy is limited by its nonresorbability and nonbioactivity. Resorbable Bioactive silica-calcium phosphate nanocomposite (SCPC75) was investigated as a novel controlled release carrier of vancomycin for the treatment of osteomyelitis. SCPC75 particles adsorbed significantly higher amount of vancomycin compared with PMMA. Moreover, SCPC75 provided a sustained release kinetics of therapeutic dose of vancomycin up to 35 days. The novel resorbable Ceramic was able to release 95.5% of the adsorbed drug in an average dose of 12 microg/mL/day over 480 h (35 days). In conjunction with the sustained drug release, a controlled dissolution rate that led to 40% mass loss of SCPC75 was observed. On the other hand, PMMA provided a sustained release of a therapeutic dose of vancomycin for 14 days after which minimal concentration of the drug was detected. Moreover, PMMA retained 32% of the drug adsorbed onto its surface. The SCPC-vancomycin implant can serve a dual function: provide a sustained therapeutic dose of antibiotic to eradicate infection and stimulate bone cell differentiation and new bone formation. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.
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A Novel Bioactive Ceramic Coating for Improved Fixation of Orthopedic Implant
MRS Proceedings, 2009Co-Authors: Ahmed El-ghannam, AniketAbstract:Electrophoretic deposition (EPD) coating of medical grade Ti-6Al-4V substrate with a novel silica-calcium phosphate nano-composite (SCPC) in the particle size range 50 nm-5 μm has been described. The influence of EPD parameters and thermal treatment on the coating homogeneity, thickness and adhesion strength has been studied. SEM analyses showed that EPD carried out in 5% (w/v) SCPC/ethanol suspension at 50 V produced a homogeneous coating on passivated Ti alloy discs. Tensile tests carried out to evaluate the adhesion strength at the Ceramic/metal interface showed that the SCPC coating layer developed adhesion strength of 47 ± 4 MPa with Ti alloy after thermal treatment at 800 °C for 1 hr. SEM – EDX analyses of the fracture surface revealed that the presence of SCPC layer on the surface of the Ti alloy indicating high interfacial stability. Upon immersion of the SCPC-coated Ti alloy substrate in PBS, a surface biological hydroxyapatite layer was deposited suggesting bone bonding ability. The successful coating of SCPC on the Ti-6Al-4V has the potential to stimulate rapid fixation and lower stress shielding by enhancing the bone bonding ability of the implant.
Paul Ducheyne - One of the best experts on this subject based on the ideXlab platform.
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5.520 – Bioactive Ceramics and Bioactive Ceramic Composite-Based Scaffolds
Comprehensive Biomaterials, 2011Co-Authors: Jinku Kim, S. Bhattacharyya, Paul DucheyneAbstract:Biodegradable polymers and Bioactive Ceramics are being combined in a variety of composite materials for tissue-engineering scaffolds. Materials and fabrication routes for three-dimensional (3D) scaffolds with interconnected high porosities suitable for bone tissue engineering are reviewed. Different polymer and Ceramic compositions applied and their impact on biodegradability and bioactivity of the scaffolds are discussed, including in vitro and in vivo assessments. The mechanical properties of today's available porous scaffolds are analyzed in detail, revealing insufficient elastic stiffness and compressive strength compared to human bone. Further challenges in scaffold fabrication for tissue engineering such as biomolecules incorporation, surface functionalization, and 3D scaffold characterization are discussed, giving possible solution strategies. Stem cell incorporation into scaffolds as a future trend is addressed briefly, highlighting the immense potential for creating next-generation synthetic/living composite biomaterials that feature high adaptiveness to the biological environment.
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in vivo evaluation of a Bioactive scaffold for bone tissue engineering
Journal of Biomedical Materials Research, 2002Co-Authors: T Livingston, Paul Ducheyne, Jonathan P GarinoAbstract:Revision cases of total hip implants are complicated by the significant amount of bone loss. New materials and/or approaches are needed to provide stability to the site, stimulate bone formation, and ultimately lead to fully functional bone tissue. Porous Bioactive glasses (prepared from 45S5 granules, 45% SiO2, 24.5% Na2O, 24.5% CaO, and 6% P2O5) have been developed as scaffolds for bone tissue engineering and have been studied in vitro. In this study, we investigated the incorporation of tissue-engineered constructs utilizing these scaffolds in large, cortical bone defects in the rat simulating revision conditions. With implantation times of 2, 4, and 12 weeks the results were compared to those using the Bioactive Ceramic scaffold alone. Two tissue-engineered constructs were studied: osteoprogenitor cells that were either seeded onto the scaffold prior to implantation (“primary”) or those that were culture expanded to form bonelike tissue on the scaffold prior to implantation (“hybrid”). Defects treated with the hybrid had the greatest amount of bone in the available pore space of the defect over all other groups at 2 weeks (p < 0.05). For both the primary and hybrid groups, woven and lamellar bone was present along the interface of the scaffold and the host cortex and within the porous space of the scaffold at 2 weeks. By 4 weeks, very uniform, lamellar bone was present throughout the scaffold for both tissue-engineered groups. The amount of bone significantly increased over time for all groups while the Bioactive Ceramic gradually resorbed by 40% at 12 weeks (p < 0.05). Structural properties of the treated long bones improved over time. Long bones treated with the hybrid had an early return in torsional stiffness by 2 weeks. Both tissue-engineered constructs achieved normal torsional strength and stiffness by 4 weeks as compared to the scaffold alone, which achieved this by 12 weeks. Porous, surface modified Bioactive Ceramic is a promising scaffold material for tissue-engineered bone repair. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 1–13, 2002
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fabrication characterization and evaluation of bioCeramic hollow microspheres used as microcarriers for 3 d bone tissue formation in rotating bioreactors
Biomaterials, 1999Co-Authors: Paul Ducheyne, Portonovo S. AyyaswamyAbstract:Novel Bioactive Ceramic hollow microspheres with an apparent density in the range 0.8–1.0 g cm-3 have been developed as microcarriers for 3-D bone tissue formation in rotating-wall vessels (RWV). Hollow Ceramic microspheres with a composition of 58–72%SiO2, 28–42%Al2O3 (wt%) and an apparent density 0.8–1.0 g cm-3 were pretreated in 1.0n NaOH for 2 h before being coated with synthesized calcium hydroxyapatite (HA) particulate sol. The HA-coated hollow microspheres were sintered for 1 h at 600, 800 and 1000°C. SEM analysis revealed that the grain size and pore size of the calcium phosphate coating increased with the sintering temperature. FTIR analysis showed that crystalline calcium hydroxyapatite was present in the coatings sintered at 600 and 800°C. When sintered at 1000°C, the coating consisted of α-tricalcium phosphate. All the coatings adhered well, independent of sintering temperature. The trajectory analysis revealed that the hollow microsphere remained suspended in a rotating-wall vessel (RWV), and experienced a low shear stress (∼0.6 dyn cm-2). Cell culture studies using rat bone marrow stromal cells and osteosarcoma cells (ROS 17/2.8) showed that the cells attached to and formed 3-D aggregates with the hollow microspheres in a RWV. Extracellular matrix was observed in the aggregates. These data suggest that these hollow Bioactive Ceramic microspheres can be used as microcarriers for 3-D bone tissue formation in vitro, as well as for the study of the effects of microgravity on bone cell functions.
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Bioactive Ceramic prosthetic coatings.
Clinical orthopaedics and related research, 1992Co-Authors: Paul Ducheyne, John M. CucklerAbstract:The concept of Bioactive Ceramic coatings on macroscopically smooth prostheses tries to reconcile opposing principles: the Ceramic with beneficial bone tissue growth effects is used as a coating since it does not have sufficient strength and toughness to be used by itself as a prosthesis material. But strength is still an issue since the coating is the primary means of transferring stresses from prosthesis to surrounding tissues. The interface between the metal core and Ceramic surface is then critical, since it essentially depends on the strength characteristics of the Ceramic. Conversely, when the Ceramic coating is used as a means to enhance bone-tissue formation around and into the prosthesis surface, thereby helping to establish a mechanical form of retention, the adhesion of Ceramic coating to metallic substrate is not critical. The optimum characteristics of the Ceramic are then those that produce the highest effect on bone-tissue growth rates immediately after surgery. The rate of bioactivity is related to the chemical reactivity of the material causing interfacial dissolution, precipitation, and ion exchange reactions. Furthermore, it also appears to depend on a substratum function affecting mineral precipitation, collagen deposition, and cellular differentiation and proliferation.
Jiao Jiao Li - One of the best experts on this subject based on the ideXlab platform.
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silk coating on a Bioactive Ceramic scaffold for bone regeneration effective enhancement of mechanical and in vitro osteogenic properties towards load bearing applications
Journal of Tissue Engineering and Regenerative Medicine, 2017Co-Authors: Jiao Jiao Li, Seyediman Roohaniesfahani, David L Kaplan, Hala ZreiqatAbstract:Bioactive Ceramic scaffolds represent competitive choices for clinical bone reconstruction, but their widespread use is restricted by inherent brittleness and weak mechanical performance under load. This study reports the development of strong and tough Bioactive scaffolds suitable for use in load-bearing bone reconstruction. A strong and Bioactive Ceramic scaffold (strontium-hardystonite-gahnite) is combined with single and multiple coating layers of silk fibroin to enhance its toughness, producing composite scaffolds which match the mechanical properties of cancellous bone and show enhanced capacity to promote in vitro osteogenesis. Also reported for the first time is a comparison of the coating effects obtained when a polymeric material is coated on Ceramic scaffolds with differing microstructures, namely the strontium-hardystonite-gahnite scaffold with high-density struts as opposed to a conventional Ceramic scaffold, such as biphasic calcium phosphate, with low-density struts. The results show that silk coating on a unique Ceramic scaffold can lead to simple and effective enhancement of its mechanical and biological properties to suit a wider range of applications in clinical bone reconstruction, and also establish the influence of Ceramic microstructure on the effectiveness of silk coating as a method of reinforcement when applied to different types of Ceramic bone graft substitutes. Copyright © 2015 John Wiley & Sons, Ltd.
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a biphasic scaffold based on silk and Bioactive Ceramic with stratified properties for osteochondral tissue regeneration
Journal of Materials Chemistry B, 2015Co-Authors: Jiao Jiao Li, Seyediman Roohaniesfahani, David L Kaplan, Hala ZreiqatAbstract:Significant clinical challenges encountered in the effective long-term treatment of osteochondral defects have inspired advancements in scaffold-based tissue engineering techniques to aid repair and regeneration. This study reports the development of a biphasic scaffold produced via a rational combination of silk fibroin and Bioactive Ceramic with stratified properties to satisfy the complex and diverse regenerative requirements of osteochondral tissue. Structural examination showed that the biphasic scaffold contained two phases with different pore morphologies to match the cartilage and bone segments of osteochondral tissue, which were joined at a continuous interface. Mechanical assessment showed that the two phases of the biphasic scaffold imitated the load-bearing behaviour of native osteochondral tissue and matched its compressive properties. In vitro testing showed that different compositions in the two phases of the biphasic scaffold could direct the preferential differentiation of human mesenchymal stem cells towards the chondrogenic or osteogenic lineage. By featuring simple and reproducible fabrication and a well-integrated interface, the biphasic scaffold strategy established in this study circumvented the common problems experienced with integrated scaffold designs and could provide an effective approach for the regeneration of osteochondral tissue.