Mark Appleford
Research interests
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InterestsRegenerative Medicine, Tissue Engineering, Scaffold, Biomedical Engineering, Mesenchymal Stem Cells
Publications
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1.98Impact points
Bilayer hydroxyapatite scaffolds for maxillofacial bone tissue engineering.
The International journal of oral & maxillofacial implants. 03/2012; 27(2):288-94.
Purpose: The frequency of alveolar ridge resorption and crestal bone loss emphasizes the clinical need for bone graft substitutes to improve local bone quality prior to dental implant placement. Microcomputed tomography has been extensively employed to estimate bone quality more objectively (ie, qua... [more] Purpose: The frequency of alveolar ridge resorption and crestal bone loss emphasizes the clinical need for bone graft substitutes to improve local bone quality prior to dental implant placement. Microcomputed tomography has been extensively employed to estimate bone quality more objectively (ie, quantitatively) by relating it to architectural parameters. In the present study, the mechanical properties of open cellular fully interconnected bilayer hydroxyapatite scaffolds, which mimicked the cortical shell/trabecular core architecture of human bone, were investigated for suitability as bone graft substitutes for maxillofacial reconstruction. Materials and Methods: Hydroxyapatite scaffolds with different architectures were fabricated using polymeric template pore sizes of 450 or 340 Μm for the inner trabecular cores and 200 or 250 Μm for the outer cortical shells in three different core-to-shell volume ratios. The architectural and mechanical properties and fluid permeability of the scaffolds were compared to reported values for maxillofacial bone. Results: Whereas the elastic moduli of the scaffolds were comparable, their compressive strength was observed to be in the lower range of human mandibular trabecular bone. The microcomputed tomography architectural indices for the scaffolds were comparable to those of human trabecular bone at different locations in the human body, including the maxilla and mandible. Scaffold compressive strength, elastic modulus, and fluid conductance were 0.3 to 2.3 MPa, 40.9 to 668.1 MPa, and 8.8 to 49.9 x 10-10 m3s-1Pa-1, respectively. Conclusion: Open-pore bilayer scaffolds can be fabricated to exhibit sufficient mechanical integrity for maxillofacial bone graft applications to match specific bone site architecture while providing sufficient permeability to sustain bone regeneration.
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2.19Impact points
Antibacterial effect and cytotoxicity of Ag-doped functionally graded hydroxyapatite coatings.
Journal of biomedical materials research. Part B, Applied biomaterials. 11/2011;
Functionally graded hydroxyapatite coatings (FGHA) doped with 1, 3, and 6.5 wt % silver (Ag) have been deposited on Titanium using ion-beam-assisted deposition. Scanning transmission electron microscopy on coating cross sections confirmed the presence of FGHA coating with mostly amorphous layers at ... [more] Functionally graded hydroxyapatite coatings (FGHA) doped with 1, 3, and 6.5 wt % silver (Ag) have been deposited on Titanium using ion-beam-assisted deposition. Scanning transmission electron microscopy on coating cross sections confirmed the presence of FGHA coating with mostly amorphous layers at the top and mostly crystalline layers toward the coating interface as well as the existence of 10-50 nm Ag particles distributed throughout the thickness of the coatings. Calcium release in phosphate buffered saline solution showed a high release rate of Ca at the beginning of the test, and a gradual decrease in release rate thereafter to a minimum level until day 7. Similarly, the release rate of Ag in ultra pure water was initially high in the first 4 h and then gradually decreased over a 7 days period. Antibacterial tests have shown a reduction in the viability of S. aureus in Ag-doped coatings particularly in samples with higher Ag concentrations of 3 and 6.5 wt %. Cytotoxicity tests using an osteoblast cell line, on the other hand, have demonstrated that the samples with 6.5 wt % Ag have a negative effect on osteoblast cell response, proliferation, and apoptosis as well as a negative effect on protein and osteocalcin production. It is notable that the samples with 3 wt % Ag or less presented minimal cytotoxicity compared with control surfaces. Considering both the antibacterial and cytotoxicity effects, it is suggested that the 3 wt % of Ag in FGHA coatings can be favorable. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
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2.82Impact points
Hydroxyapatite/polylactide biphasic combination scaffold loaded with dexamethasone for bone regeneration.
Journal of biomedical materials research. Part A. 09/2011; 99(4):638-47.
This study presents a novel design of a ceramic/polymer biphasic combination scaffold that mimics natural bone structures and is used as a bone graft substitute. To mimic the natural bone structures, the outside cortical-like shells were composed of porous hydroxyapatite (HA) with a hollow interior ... [more] This study presents a novel design of a ceramic/polymer biphasic combination scaffold that mimics natural bone structures and is used as a bone graft substitute. To mimic the natural bone structures, the outside cortical-like shells were composed of porous hydroxyapatite (HA) with a hollow interior using a polymeric template-coating technique; the inner trabecular-like core consisted of porous poly(D,L-lactic acid) (PLA) that was loaded with dexamethasone (DEX) and was directly produced using a particle leaching/gas forming technique to create the inner diameter of the HA scaffold. It was observed that the HA and PLA parts of the fabricated HA/PLA biphasic scaffold contained open and interconnected pore structures, and the boundary between both parts was tightly connected without any gaps. It was found that the structure of the combination scaffold was analogous to that of natural bone based on micro-computed tomography analysis. Additionally, the dense, uniform apatite layer was formed on the surface of the HA/PLA biphasic scaffold through a biomimetic process, and DEX was successfully released from the PLA of the biphasic scaffold over a 1-month period. This release caused human embryonic palatal mesenchyme cells to proliferate, differentiate, produce ECM, and form tissue in vitro. Therefore, it was concluded that this functionally graded scaffold is similar to natural bone and represents a potential bone-substitute material.
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5.95Impact points
Porous hydroxyapatite scaffold with three-dimensional localized drug delivery system using biodegradable microspheres.
Journal of controlled release : official journal of the Controlled Release Society. 03/2011; 153(2):133-40.
In this study, ionic immobilization of dexamethasone (DEX)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres was performed on the hydroxyapatite (HAp) scaffold surfaces. It was hypothesized that in vivo bone regeneration could be enhanced with HAp scaffolds containing DEX-loaded PLGA microsph... [more] In this study, ionic immobilization of dexamethasone (DEX)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres was performed on the hydroxyapatite (HAp) scaffold surfaces. It was hypothesized that in vivo bone regeneration could be enhanced with HAp scaffolds containing DEX-loaded PLGA microspheres compared to the use of HAp scaffolds alone. In vitro drug release from the encapsulated microspheres was measured prior to the implantation in the femur defects of beagle dogs. It was observed that porous, interconnected HAp scaffolds as well as DEX-loaded PLGA microspheres were successfully fabricated in this study. Additionally, PEI was successfully coated on PLGA microsphere surfaces, resulting in a net positive-charged surface. With such modification of the PLGA microsphere surfaces, DEX-loaded PLGA microspheres were immobilized on the negatively charged HAp scaffold surfaces. Release profile of DEX over a 4week immersion study indicated an initial burst release followed by a sustained release. In vivo evaluation of the defects filled with DEX-loaded HAp scaffolds indicated enhanced volume and quality of new bone formation when compared to defects that were either unfilled or filled with HAp scaffolds alone. This innovative platform for bioactive molecule delivery more potently induced osteogenesis in vivo, which may be exploited in implantable bone graft substitutes for stem cell therapy or improved in vivo performance. It was thus concluded that various bioactive molecules for bone regeneration might be efficiently incorporated with calcium phosphate-based bioceramics using biodegradable polymeric microspheres.
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1.96Impact points
In vivo performance of bilayer hydroxyapatite scaffolds for bone tissue regeneration in the rabbit radius.
Journal of materials science. Materials in medicine. 02/2011; 22(3):647-56.
The objective of this study was to investigate the in vivo biomechanical performance of bone defects implanted with novel bilayer hydroxyapatite (HAp) scaffolds that mimic the cortical and cancellous organization of bone. The scaffolds maintained architectural continuity in a rabbit radius segmental... [more] The objective of this study was to investigate the in vivo biomechanical performance of bone defects implanted with novel bilayer hydroxyapatite (HAp) scaffolds that mimic the cortical and cancellous organization of bone. The scaffolds maintained architectural continuity in a rabbit radius segmental defect model and were compared to an untreated defect group (negative control) and autologous bone grafts (positive control). Micro-CT evaluations indicated total bone and scaffold volume in the experimental group was significantly greater than the defect group but lesser than the autologous bone graft treatment. The flexural toughness of the scaffold and the autograft groups was significantly greater than the flexural toughness of the defect group. Interestingly, the absolute density of the bone mineral as well as calcium to phosphorus (Ca/P) ratio in that mineral for the scaffold and autograft contralateral bones was significantly higher than those for the defect contralaterals suggesting that the scaffolds contributed to calcium homeostasis. It was concluded from this study that new bone regenerated in the bilayer HAp scaffolds was comparable to the empty defects and while the HAp scaffolds provided significant increase in modulus when compared to empty defect and their flexural toughness was comparable to autografts after 8 weeks of implantation.
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3.98Impact points
Stability of antibacterial self-assembled monolayers on hydroxyapatite.
Acta biomaterialia. 02/2010; 6(8):3242-55.
Open fractures are common in battlefields, motor vehicle accidents, gunshot wounds, sports injuries, and high-energy falls. Such fractures are treated using hydroxyapatite (HA)-based bone graft substitutes. However, open fracture wounds are highly susceptible to bacterial infections. Hence, this stu... [more] Open fractures are common in battlefields, motor vehicle accidents, gunshot wounds, sports injuries, and high-energy falls. Such fractures are treated using hydroxyapatite (HA)-based bone graft substitutes. However, open fracture wounds are highly susceptible to bacterial infections. Hence, this study was focused on incorporating antibacterial properties to HA using silver (Ag) carrying self-assembled monolayers (SAMs). Also, the stability of Ag carrying SAMs on HA was investigated under sterilization and physiological conditions. Initially, the -COOH terminated phosphonic acid SAMs of two different chain lengths (11 carbon atoms - shorter chain and 16 carbon atoms - longer chain) were deposited on HA. Antibacterial SAMs (ASAMs) were prepared by chemically attaching Ag to shorter and longer chain SAMs coated HA. X-ray photoelectron spectroscopy, atomic force microscopy, and contact angle goniometry collectively confirmed the attachment of Ag onto SAMs coated HA. The bacterial adhesion study showed that the adherence of Staphylococcus aureus was significantly reduced on ASAMs coated HA when compared to control-HA. The stability studies showed that gas plasma, dry heat and autoclave degraded most of the ASAMs on HA. UV irradiation did not damage the shorter chain ASAMs as vigorously as other treatments, while it degraded the longer chain ASAMs completely. Ethylene oxide treatment did not degrade the longer chain ASAMs unlike all other treatments but it severely damaged the shorter chain ASAMs. Both shorter and longer chain ASAMs significantly desorbed from the HA surfaces under physiological conditions although longer chain ASAMs exhibited better stability than shorter chain ASAMs. This study demonstrated the potential for using ASAMs to provide antibacterial properties to HA and the need for developing techniques to improve stability of SAMs under sterilization and physiological conditions.
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3.98Impact points
Deposition and investigation of functionally graded calcium phosphate coatings on titanium.
Acta biomaterialia. 06/2009;
A series of calcium phosphate coatings with graded crystallinity were deposited onto heated titanium substrates using ion beam assisted deposition. The microstructure of the coating was examined using transmission electron microscopy (TEM). The coating thickness observed to be in a range of 594-694n... [more] A series of calcium phosphate coatings with graded crystallinity were deposited onto heated titanium substrates using ion beam assisted deposition. The microstructure of the coating was examined using transmission electron microscopy (TEM). The coating thickness observed to be in a range of 594-694nm. The degree of crystallinity and microstructural grain size of the coating showed a clear decrease with increasing distance from the substrate-coating interface. Fourier transform infrared spectroscopy (FTIR) confirmed the presence of PO(4)(3-), and X-ray photoelectron spectroscopy (XPS) analysis on the coating top surface showed that the atomic Ca/P ratio was in the range of 1.52+/-0.15 to 1.61+/-0.07. The biological response to the coatings was also evaluated using an osteoblast precursor cell culture test. More cells and a higher integrin expression of cell attachment sites were observed on the coating surface when compared to the control group (blank titanium surface). The pull-off test showed average adhesion strengths at the coating-substrate interface to be higher than 85.12+/-5.37MPa. Nanoindentation tests indicated that the Young's moduli of all coatings are higher than 91.747+/-3.641GPa and microhardness values are higher than 5.275+/-0.315GPa. While the adhesion strength results helped us to identify the best setup for substrate temperature and processing parameters to begin the deposition, the culture test and XPS results helped identifying the optimum parameters for the last stage of deposition. TEM, X-ray diffraction, FTIR and nanoidentation results were used to further evaluate the quality of the coating and optimization of its processing parameters.
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Structure and Characteristics of Novel Hydroxyapatite/Polylactide Bi-Layered Porous Scaffold for Bone Regeneration
Tissue Engineering and Regenerative Medicine. 01/2009; 6(13):1241-1251.
Abstract : The goal of this study was to develop novel hydroxyapatite (HAp)/ polylactide (PLA) bi-layered porous scaffold for tissue-engineered bone regeneration. To mimic normal bone structures, the outside cortical-like shells fabricated consisted of porous HAp and an inner trabecular-like core wa... [more] Abstract : The goal of this study was to develop novel hydroxyapatite (HAp)/ polylactide (PLA) bi-layered porous scaffold for tissue-engineered bone regeneration. To mimic normal bone structures, the outside cortical-like shells fabricated consisted of porous HAp and an inner trabecular-like core was made of porous PLA. Cortical-like porous HAp scaffolds with hollow in its inside was fabricated using a polymer sponge template. Trabecular-like porous PLA scaffold was directly formed by a particle leaching/gas foaming technique with sodium percarbonate as a novel porogen in inner diameter of HA scaffolds. The oxygen plasma treatment was performed to modify the PLA surface of bi-layered porous scaffold. The plasma-treated bi-layered scaffold was subsequently dipped in an alcoholic solution containing calcium and phosphate ions to deposit precursors on the surface. The surface modified bi-layered scaffold was immersed in simulated body fluid (SBF) at 5 times ionic concentration for 24 hr to obtain the final bonelike apatite coated HAp/PLA bi-layered porous scaffold. It was observed that the HAp and PLA parts of fabricated bi-layered scaffolds contain open and interconnected pore structures, with no structural delaminations on the external surfaces. Using helium pycnometry, the maximum porosity was observed to be greater than 96% for bi-layered scaffold. Additionally, the distribution of pore size for the PLA scaffolds was from 100 to 700 μm. Also, the dense and uniform bone-like apatite layer was successfully formed on surface of HAp/PLA bi-layered scaffold after immersion for 1 day in SBF solution. Total protein and alkaline phosphatase (ALP) content of bi-layered scaffold were higher than the control HAp scaffold during 4 weeks in vitro culture study using human embryonic palatal mesenchymal (HEPM) cells. It is indicated that bi-layered porous scaffold has stronger ability to induce HEPM cell attachment, proliferation, differentiation, and mineralization than that of the control HAp porous scaffold. The resulting apatite coated HAp/PLA bi-layered porous scaffold is more bioactive that might be applicable as a promising scaffold for osteogenesis.
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2.82Impact points
In vivo study on hydroxyapatite scaffolds with trabecular architecture for bone repair.
Journal of biomedical materials research. Part A. 06/2008;
The objective of this research was to investigate the bone formation and angio-conductive potential of hydroxyapatite (HA) scaffolds closely matched to trabecular bone in a canine segmental defect after 3 and 12 weeks post implantation. Histomorphometric comparisons were made between naturally formi... [more] The objective of this research was to investigate the bone formation and angio-conductive potential of hydroxyapatite (HA) scaffolds closely matched to trabecular bone in a canine segmental defect after 3 and 12 weeks post implantation. Histomorphometric comparisons were made between naturally forming trabecular bone (control) and defects implanted with scaffolds fabricated with micro-size (M-HA) and nano-size HA (N-HA) ceramic surfaces. Scaffold architecture was similar to trabecular bone formed in control defects at 3 weeks. No significant differences were identified between the two HA scaffolds; however, significant bone in-growth was observed by 12 weeks with 43.9 +/- 4.1% and 50.4 +/- 8.8% of the cross-sectional area filled with mineralized bone in M-HA and N-HA scaffolds, respectively. Partially organized, lamellar collagen fibrils were identified by birefringence under cross-polarized light at both 3 and 12 weeks post implantation. Substantial blood vessel infiltration was identified in the scaffolds and compared with the distribution and diameter of vessels in the surrounding cortical bone. Vessels were less numerous but significantly larger than native cortical Haversian and Volkmann canals reflecting the scaffold architecture where open spaces allowed interconnected channels of bone to form. This study demonstrated the potential of trabecular bone modeled, highly porous and interconnected, HA scaffolds for regenerative orthopedics. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.
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2.82Impact points
Design and characterization of a novel chitosan/nanocrystalline calcium phosphate composite scaffold for bone regeneration.
Journal of biomedical materials research. Part A. 03/2008;
To meet the challenge of regenerating bone lost to disease or trauma, biodegradable scaffolds are being investigated as a way to regenerate bone without the need for an auto- or allograft. Here, we have developed a novel microsphere-based chitosan/nanocrystalline calcium phosphate (CaP) composite sc... [more] To meet the challenge of regenerating bone lost to disease or trauma, biodegradable scaffolds are being investigated as a way to regenerate bone without the need for an auto- or allograft. Here, we have developed a novel microsphere-based chitosan/nanocrystalline calcium phosphate (CaP) composite scaffold and investigated its potential compared to plain chitosan scaffolds to be used as a bone graft substitute. Composite and chitosan scaffolds were prepared by fusing microspheres of 500-900 mum in diameter, and porosity, degradation, compressive strength, and cell growth were examined. Both scaffolds had porosities of 33-35% and pore sizes between 100 and 800 mum. However, composite scaffolds were much rougher and, as a result, had 20 times more surface area/unit mass than chitosan scaffolds. The compressive modulus of hydrated composite scaffolds was significantly higher than chitosan scaffolds (9.29 +/- 0.8 MPa vs. 3.26 +/- 2.5 MPa), and composite scaffolds were tougher and more flexible than what has been reported for other chitosan-CaP composites or CaP scaffolds alone. Using X-ray diffraction, scaffolds were shown to contain partially crystalline hydroxyapatite with a crystallinity of 16.7% +/- 6.8% and crystallite size of 128 +/- 55 nm. Fibronection adsorption was increased on composite scaffolds, and cell attachment was higher on composite scaffolds after 30 min, although attachment rates were similar after 1 h. Osteoblast proliferation (based on dsDNA measurements) was significantly increased after 1 week of culture. These studies have demonstrated that composite scaffolds have mechanical properties and porosity sufficient to support ingrowth of new bone tissue, and cell attachment and proliferation data indicate composite scaffolds are promising for bone regeneration. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.
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4.47Impact points
A cellular perspective to bioceramic scaffolds for bone tissue engineering: the state of the art.
Current topics in medicinal chemistry. 02/2008; 8(4):290-9.
A vast number of manufacturing techniques have been employed in the last five years to manufacture three dimensional (3D) calcium phosphate (CaP) scaffolds, with the intention to replicate the architecture of native bone as well as to repair and restore bone function. Design features such as archite... [more] A vast number of manufacturing techniques have been employed in the last five years to manufacture three dimensional (3D) calcium phosphate (CaP) scaffolds, with the intention to replicate the architecture of native bone as well as to repair and restore bone function. Design features such as architectural control and sintering temperature and their impact on scaffold performance is presented in this review. In vitro cell responses to bioceramic scaffolds and their in vivo performances have been enhanced. Current frontiers of active research on HA scaffolds have included the relationship between fluid flow and mechanotransduction as well as cell signaling pathways that induce endothelial cell recruitment and angiogenesis. Additionally, current research has focused on a better understanding of cell signaling and its environmental cues. The availability of non-invasive and non-destructive quantitative imaging modalities has also become critical in aiding the characterization of scaffolds and predicting scaffold performance. It is thus anticipated that further knowledge gained from this research will allow the overall advancement of scaffolds that can be clinically used to restore large bone defects.
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7.88Impact points
Ultrasound effect on osteoblast precursor cells in trabecular calcium phosphate scaffolds.
Biomaterials. 12/2007; 28(32):4788-94.
This study investigated the in vitro effect of low-intensity pulsed ultrasound (LIPUS) on human embryonic palatal mesenchyme cells (HEPM, CRL-1486, ATCC, Manassas, VA), an osteoblast precursor cell line, during early adhesion to calcium phosphate scaffolds. Hydroxyapatite (HA) and beta-tricalcium ph... [more] This study investigated the in vitro effect of low-intensity pulsed ultrasound (LIPUS) on human embryonic palatal mesenchyme cells (HEPM, CRL-1486, ATCC, Manassas, VA), an osteoblast precursor cell line, during early adhesion to calcium phosphate scaffolds. Hydroxyapatite (HA) and beta-tricalcium phosphate (TCP) ceramic scaffolds were produced by a template coating method. Phospho-specific antibody cell-based ELISA (PACE) technique was utilized on stress activation proteins, including the extracellular signal-regulated kinase (ERK1/2), P38, c-Jun N-terminal kinase (JNK) and the anti-apoptosis mediator protein kinase B (PKB/AKT). Cell-based ELISAs were also performed on the membrane anchoring protein vinculin and alpha6beta4 integrin. LIPUS stimulated activation of PERK 1/2, PJNK, PP38 and vinculin in traditional two-dimensional (2-D) culture. Calcium release from the scaffolds was partially involved in the activation of PERK 1/2 when cell response was compared between culture on 2-D surfaces and three-dimensional (3-D) HA and TCP scaffolds. Effects of calcium extracted media from scaffolds alone could not account for the full activation of PJNK, PP38, PAKT, vinculin and alpha6beta4 integrin. LIPUS stimulation further increased PERK activity on TCP scaffolds corresponding with an increase in both vinculin and alpha6beta4 integrin levels. It was concluded from this study that LIPUS treatment can significantly affect stress signaling mediators and adhesion proteins in osteoblast precursor cells during the early cell-attachment phase to trabecular patterned scaffolds.
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2.82Impact points
Antibacterial and osteogenic properties of silver-containing hydroxyapatite coatings produced using a sol gel process.
Journal of biomedical materials research. Part A. 10/2007; 82(4):899-906.
Since bacterial infection is a rising complication following the wide use of implant, there is considerable attention on the effect of implant surface properties on bacterial adhesion. In this study, the effect of silver (Ag) doped hydroxyapatite (HA) coatings on initial antibacterial adhesion and o... [more] Since bacterial infection is a rising complication following the wide use of implant, there is considerable attention on the effect of implant surface properties on bacterial adhesion. In this study, the effect of silver (Ag) doped hydroxyapatite (HA) coatings on initial antibacterial adhesion and osteoblast cell proliferation and differentiation was investigated. Using a sol-gel process, HA coatings doped with 1 wt % AgNO(3) (AgHA1.0) and 1.5 wt % Ag (AgHA1.5) were prepared. Coated surfaces were characterized using X-ray diffraction (XRD) and contact angles measurements. The initial bacteria adhesion was evaluated using a RP12 strain of Staphylococcus epidermidis (ATCC 35984) and the Cowan I strain of Staphylococcus aureus, whereas osteoblast proliferation and differentiation were evaluated using human embryonic palatal mesenchyme cells (HEPM), an osteoblast precursor cell line. In this study, XRD analysis of all surfaces indicated peaks corresponding to HA. Contact angles for AgHA surfaces were observed to be significantly lower when compared to HA surfaces. In vitro initial bacterial adhesion study indicated a significantly reduced number of S. epidermidis and S. aureus on AgHA surfaces when compared to HA surface. The use of HEPM cells indicated no significant difference in double-stranded DNA (dsDNA) production between all surfaces. Additionally, no differences in alkaline phosphatase specific activity were observed between HA and AgHA1.0 surfaces. Overall, it was concluded that AgHA1.0 has the similar biological activity as HA, with respect to bone cell proliferation and differentiation. In addition, the AgHA1.0 was also concluded to have the ability to minimize the initial bacteria adhesion. (c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007.
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7.88Impact points
Effects of trabecular calcium phosphate scaffolds on stress signaling in osteoblast precursor cells.
Biomaterials. 07/2007; 28(17):2747-53.
The objective of this research was to investigate stress-signaling patterns in response to two-dimensional (2-D) and three-dimensional (3-D) calcium phosphate (CP) materials using human embryonic palatal mesenchyme cells (HEPM, CRL-1486, ATCC, Manassas, VA), an osteoblast precursor cell line. Contro... [more] The objective of this research was to investigate stress-signaling patterns in response to two-dimensional (2-D) and three-dimensional (3-D) calcium phosphate (CP) materials using human embryonic palatal mesenchyme cells (HEPM, CRL-1486, ATCC, Manassas, VA), an osteoblast precursor cell line. Control discs and scaffolds were fabricated from hydroxyapatite and beta tri-CP ceramics. Phospho-specific antibody cell-based ELISA technique was utilized on members of the mitogen-activated protein kinase cascade including; the extracellular signal-regulated kinases (ERK1/2), p38, c-Jun N-terminal kinase (JNK), and the anti-apoptosis mediator protein kinase B (AKT). Quantification of these signals was evaluated during the early attachment phase of osteoblast precursor cells. In this study, it was observed that 3-D CP scaffolds significantly activated the stress mediators p38 and JNK but not ERK1/2. This signal trend was matched with an up-regulation in AKT, suggesting the ability of cells to manage high stress signals in response to 3-D CP architecture and that 3-D CP scaffolds are necessary for studies simulating a natural trabecular bone organization. The absence of these signals in 2-D CP surfaces indicated the importance of local architecture conditions on cell stress response. It was concluded from this study that osteoblast precursor cells cultured in 3-D CP scaffolds experience greater stress-signaling patterns when compared to 2-D CP surfaces.
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1.51Impact points
The integration of chitosan-coated titanium in bone: an in vivo study in rabbits.
Implant dentistry. 04/2007; 16(1):66-79.
PROCEDURE: Much research is directed at surface modifications to enhance osseointegration of implants. A new potential coating is the biopolymer, chitosan, the deacetylated derivative of the natural polysaccharide, chitin. Chitosan is biocompatible, degradable, nontoxic, and exhibits osteogenic prop... [more] PROCEDURE: Much research is directed at surface modifications to enhance osseointegration of implants. A new potential coating is the biopolymer, chitosan, the deacetylated derivative of the natural polysaccharide, chitin. Chitosan is biocompatible, degradable, nontoxic, and exhibits osteogenic properties. The aim of this research was to investigate the hypothesis that chitosan-coated titanium supports bone formation and osseointegration. MATERIALS AND METHODS: Chitosan (1 wt% of 92.3% deacetylated chitosan in 1% acetic acid) was solution cast and bonded to rough ground titanium pins (2-mm diameterx4-mm long) via silane reactions. Calcium phosphate sputter-coated titanium and uncoated titanium pins were used as controls. Two chitosan-coated pins, and 1 each of calcium phosphate coated and uncoated pins were implanted unilaterally in the tibia of 16 adult male New Zealand white rabbits. At 2, 4, 8, and 12 weeks, undecalcified sections were histologically evaluated for healing and bone formation. RESULTS: Histological evaluations of tissues in contact with the chitosan-coated pins indicated minimal inflammatory response and a typical healing sequence of fibrous, woven bone formation, followed by development of lamellar bone. These observations were similar to those for tissues interfacing the control calcium phosphate-coated and uncoated titanium implants. Quantitative comparisons of the bone-implant interface were not possible since 31% of the implants migrated into the tibial marrow space after implantation due to insufficient cortical bone thickness to hold pins in place during healing. CONCLUSION: These data support the hypothesis that chitosan-coatings are able to develop a close bony apposition or the osseointegration of dental/craniofacial and orthopedic implants.
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Bioceramics for Tissue Engineering Applications – A Review
American Journal of Biochemistry and Biotechnology. 01/2006;
Three dimensional (3-D) scaffolds have been explored in an attempt to persuade the body toheal or repair tissues that do not do so spontaneously. Considerable advances in tissue engineering andregeneration have been accomplished over the last decade. However, the material and 3-D scaffoldsideal for ... [more] Three dimensional (3-D) scaffolds have been explored in an attempt to persuade the body toheal or repair tissues that do not do so spontaneously. Considerable advances in tissue engineering andregeneration have been accomplished over the last decade. However, the material and 3-D scaffoldsideal for optimal regeneration of missing or lost tissues has not been identified. While currentmaterials and techniques have met with varying successes, each exhibits limitations that must beaddressed. In addition, despite the large amount of research in the area of 3-D scaffolds for bone tissueengineering that has been performed over the past decade, there is an overall lack of success inbringing this technology to the clinic, especially for porous scaffolds used to restore large bone defects.This review paper will focus on the use of calcium phosphate (CaP) materials used for tissueengineering, the different known methods of scaffold synthesis, and some of the significant in vitro, invivo, and clinical outcomes when these CaP scaffolds were used in patients.
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1.98Impact points
Effect of chemically modified titanium surfaces on protein adsorption and osteoblast precursor cell behavior.
The International journal of oral & maxillofacial implants. 22(4):542-50.
PURPOSE: To investigate the effects of different chemically modified titanium surfaces on protein adsorption and the osteoblastic differentiation of human embryonic palatal mesenchymal (HEPM) cells. MATERIALS AND METHODS: Three different surfaces were evaluated. The first, a machined surface (Ti-M),... [more] PURPOSE: To investigate the effects of different chemically modified titanium surfaces on protein adsorption and the osteoblastic differentiation of human embryonic palatal mesenchymal (HEPM) cells. MATERIALS AND METHODS: Three different surfaces were evaluated. The first, a machined surface (Ti-M), was considered a control. The second surface was acid etched (Ti-AE). The third surface was prepared by exposing the Ti-AE samples to sodium hydroxide (NaOH) solution (Ti-AAE). The surface characteristics of chemically modified titanium were investigated by means of scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and profilometry. To evaluate the production of biomarkers, commercial kits were utilized. RESULTS: Surface composition and morphology affected the kinetics of protein adsorption. Ti-AE surfaces manifested a greater affinity for fibronectin adsorption compared to Ti-M or Ti-AAE surfaces. It was observed that Ti-AE and Ti-AAE surfaces promoted significantly greater cell attachment compared to Ti-M surfaces. Statistically significant differences were also observed in the expression of alkaline phosphatase (ALP) activity, osteocalcin, and osteopontin on all 3 titanium surfaces. ALP activity and osteocalcin production up to day 12 suggested that differentiation of the cells into osteoblasts had occurred and that cells were expressing a bone-forming phenotype. CONCLUSIONS: It was thus concluded from this study that surface morphology and composition play a critical role in enhancing HEPM cell proliferation and differentiation into osteoblast cells.
Following (3)
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Jesus Hernandez
University of Texas at San Antonio -
Joseph C Wenke
United States Army Institute of Surgical Research -
Teja Guda
University of Texas at San Antonio
