This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
In vitro measurement of the chemical changes occurring within β-tricalcium phosphate bone graft s... more In vitro measurement of the chemical changes occurring within β-tricalcium phosphate bone graft substitutes,
Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2017
This study introduced and demonstrated a new method to investigate the repair process of bone def... more This study introduced and demonstrated a new method to investigate the repair process of bone defects using micro-and macroporous beta-tricalcium phosphate (b-TCP) substitutes. Specifically, the new method combined and aligned histology, SEM, and preimplantation microcomputed tomography (mCT) data to accurately characterize tissue phases found in biopsies, and thus better understand the bone repair process. The results included (a) the exact fraction of ceramic remnants (CR); (b) the fraction of ceramic resorbed and substituted by bone (CSB); and (c) the fraction of ceramic resorbed and not substituted by bone (CNSB). The new method allowed in particular the detection and quantification of mineralized tissues within the 1-10 mm micropores of the ceramic ("micro-bone"). The utility of the new method was demonstrated by applying it on biopsies of two b-tricalcium phosphate bone substitute groups with two differing macropore sizes implanted in an ovine model for 6 weeks. The total bone deposition and ceramic resorption of the two substitute groups, having macropore sizes of 510 and 1220 lm, were 25.1 6 8.1% and 67.5 6 3.2%, and 24.4 6 4.1% and 61.4 6 6.5% for the group having the larger pore size. V
Objective: The aim of this study was to produce a novel composite of microporous β-TCP filled wit... more Objective: The aim of this study was to produce a novel composite of microporous β-TCP filled with alginate and Vancomycin (VAN) to prolong the release behavior of the antibiotic for up to 28 days. Material and Methods: Using the flow chamber developed by the group, porous ceramics in a directional flow were filled with alginates of different composition containing 50 mg/mL of antibiotics. After cross-linking the alginate with calcium ions, incubation took place in 10 mL double-distilled water for 4 weeks at 37 °C. At defined times (1, 2, 3, 6, 9, 14, 20 and 28 days), the liquid was completely exchanged and analyzed by capillary zone electrophoresis and microtiter trials. For statistical purposes, the mean and standard deviation were calculated and analyzed by ANOVA. Results: The release of VAN from alginate was carried out via an external calcium source over the entire period with concentrations above the minimal inhibitory concentration (MIC). The burst release measured 35.2 ± 1.5%. The release of VAN from alginate with an internal calcium source could only be observed over 14 days. The burst release here was 61.9 ± 4.3%. The native alginate's burst release was 54.1 ± 7.8%; that of the sterile alginate 40.5 ± 6.4%. The microtiter experiments revealed efficacy over the entire study period for VAN. The MIC value was determined in the release experiments as well in a range of 0.5-2.0 µg/mL against Staphylococcus aureus.
Various compositions of synthetic calcium phosphates (CaP) have been proposed and their use has c... more Various compositions of synthetic calcium phosphates (CaP) have been proposed and their use has considerably increased over the past decades. Besides differences in physicochemical properties, resorption and osseointegration, artificial CaP bone graft might differ in their resistance against biofilm formation. We investigated standardised cylinders of 5 different CaP bone grafts (cyclOS, chronOS (both β-TCP (tricalcium phosphate)), dicalcium phosphate (DCP), calcium-deficient hydroxyapatite (CDHA) and α-TCP). Various physico-chemical characterisations e.g., geometrical density, porosity, and specific surface area were investigated. Biofilm formation was carried out in tryptic soy broth (TSB) and human serum (SE) using Staphylococcus aureus (ATCC 29213) and S. epidermidis RP62A (ATCC 35984). The amount of biofilm was analysed by an established protocol using sonication and microcalorimetry. Physico-chemical characterisation showed marked differences concerning macro-and micropore size, specific surface area and porosity accessible to bacteria between the 5 scaffolds. Biofilm formation was found on all scaffolds and was comparable for α-TCP, chronOS, CDHA and DCP at corresponding time points when the scaffolds were incubated with the same germ and/or growth media, but much lower for cyclOS. This is peculiar because cyclOS had an intermediate porosity, mean pore size, specific surface area, and porosity accessible to bacteria. Our results suggest that biofilm formation is not influenced by a single physico-chemical parameter alone but is a multi-step process influenced by several factors in parallel. Transfer from in vitro data to clinical situations is difficult; thus, advocating the use of cyclOS scaffolds over the four other CaP bone grafts in clinical situations with a high risk of infection cannot be clearly supported based on our data.
Micro-computed tomography (microCT) is commonly used to characterize the three-dimensional struct... more Micro-computed tomography (microCT) is commonly used to characterize the three-dimensional structure of bone graft scaffolds before and after implantation in order to assess changes occurring during implantation. The accurate processing of the microCT datasets of explanted β-tricalcium phosphate (β-TCP) scaffolds poses significant challenges because of (a) the overlap in the grey values distribution of ceramic remnants, bone, and soft tissue, and of (b) the resorption of the bone substitute during the implantation. To address those challenges, this article introduces and rigorously validates a new processing technique to accurately distinguish these three phases found in the explanted β-TCP scaffolds. Specifically, the microCT datasets obtained before and after implantation of β-TCP scaffolds were aligned in 3D, and the characteristic grey value distributions of the three phases were extracted, thus allowing for (i) the accurate differentiation between these three phases (ceramic re...
β-Tricalcium phosphate (β-TCP) platelets synthesized in ethylene glycol offer interesting geometr... more β-Tricalcium phosphate (β-TCP) platelets synthesized in ethylene glycol offer interesting geometries for nano-structured composite bone substitutes but were never crystallographically analyzed. In this study, powder X-ray diffraction and Rietveld refinement revealed a discrepancy between the platelet structure and the known β-TCP crystal model. In contrast, a model featuring partial H for Ca substitution and the inversion of P1O4 tetrahedra, adopted from the whitlockite structure, allowed for a refinement with minimal misfits and was corroborated by HPO4(2-) absorptions in Fourier-transform IR spectra. The Ca/P ratio converged to 1.443 ± 0.003 (n = 36), independently of synthesis conditions. As a quantitative verification, the platelets were thermally decomposed into hydrogen-free β-TCP and β-calcium pyrophosphate which resulted in a global Ca/P ratio in close agreement with the initial β-TCP Ca/P ratio (ΔCa/P = 0.003) and with the chemical composition measured by inductively couple...
Little is known regarding the associations between sex-hormone levels, sex, body mass index (BMI)... more Little is known regarding the associations between sex-hormone levels, sex, body mass index (BMI), age, other host factors and biomaterial stimulated bone regeneration in the human craniofacial skeleton. The aim of this study was to elucidate the associations between these factors and bone formation after sinus floor augmentation procedures (SFA) utilizing a bioactive tricalcium phosphate (TCP) bone grafting material. We conducted a prospective study in a human population in which 60 male and 60 female participants underwent SFA and dental implant placement using a staged approach. BMI as well as levels of serum estradiol (E2), total testosterone (TT), and the free androgen index (FAI) were measured by radioimmunoassay and electrochemoluminescent-immunoassay. At implant placement, 6 months after SFA, bone biopsy specimens were harvested for hard tissue histology, the amount of bone formation was evaluated by histomorphometry and immunohistochemical analysis of osteogenic marker expression. The Wilcoxon rank-sum U test, Spearman correlations and linear regression analysis were used to explore the association between bone formation and BMI, hormonal and other host factors. BMI and log E2 were significantly positively associated with bone formation in male individuals (p < 0.05). Histomorphometry revealed trends toward greater bone formation and osteogenic marker expression with non-smokers compared to smokers. In male patients, higher E2 levels and higher BMI enhanced TCP stimulated craniofacial i.e. intramembranous bone repair.
NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteo... more NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteochondral cells. It was widely used in bone regeneration research by loading onto carriers such as tricalcium phosphate (TCP) particles. However, there has been little research on protein controlled release from this material and its potential application. In this study, TCP was first modified with a hydroxyapatite coating followed by a chitosan coating to prepare chitosan/hydroxyapatite-coated TCP particles (Chi/HA-TCP). The preparation was characterized by SEM, EDX, FTIR, XRD, FM and Zeta potential measurements. The NELL-1 loaded Chi/HA-TCP particles and the release kinetics were investigated in vitro. It was observed that the Chi/HA-TCP particles prepared with the 0.3% (wt/wt) chitosan solution were able to successfully control the release of NELL-1 and maintain a slow, steady release for up to 28 days. Furthermore, more than 78% of the loaded protein's bioactivity was preserved in Chi/HA-TCP particles over the period of the investigation, which was significantly higher than that of the protein released from hydroxyapatite coated TCP (HA-TCP) particles. Collectively, this study suggests that the osteogenic protein NELL-1 showed a sustained release pattern after being encapsulated into the modified Chi/HA-TCP particles, and the NELL-1 integrated composite of Chi/HA-TCP showed a potential to function as a protein delivery carrier and as an improved bone matrix for use in bone regeneration research. 2016 Elsevier B.V. All rights reserved.
Frontiers in Bioengineering and Biotechnology, 2016
most likely treatment option, often in conjunction with a bone graft to stimulate healing. [1] Bo... more most likely treatment option, often in conjunction with a bone graft to stimulate healing. [1] Bone grafting using autologous or allograft bone is the "gold standard" but there are associated limitations; a second surgical procedure with related donor-site morbidity, concerns of immunogenicity, and demand outweighing supply. [2-4] This has led to a demand for synthetic bone grafts but to date commercially available synthetic grafts have been unable to match the clinical results seen with autograft. [2,5] Ideally synthetic bone grafts should be biocompatible, integrate with the bone resorption process, and aid new bone ingrowth while retaining sufficient mechanical strength. Resorbable materials that can utilize the bone's natural remodeling process to degrade, releasing nontoxic by-products that can be easily metabolized by the body, are very attractive for use as bone graft substitutes. However, some alleged resorbable bone graft substitutes have been detected years after in vivo implantation. [6,7] Innovation of porous scaffolds with an interconnected pore structure has allowed for increased bone ingrowth [8-11] and subsequent increased rate of resorption in vivo. [12-15] The introduction of porosity has caused a new challenge for researchers when measuring bioresorption of new materials, rendering the traditional in vitro methods insufficient. The traditional methods used to assess resorbability of bone substitutes in vitro are osteoclast (OC) formation indicated by tartrateresistant acid phosphatase (TRAP) expression and a cell-based resorption assay, alternatively known as a "pit" assay, developed by Boyde et al. [16] and Chambers et al. [17] Initially developed as an assay to investigate OC biology using dentine or bone as a substrate, it is now routinely used to understand biomaterial resorption. OCs are cultured on biomaterial surfaces for specific periods and then detached, at which point the excavated areas (pits) beneath the cells can be analyzed by scanning electron microscopy (SEM) in terms of pit number, pit area, or pit volume. The simplest method is to determine the number of pits, which can be quantified using reflected light microscopy, where staining is not required, [18] or by light microscopy (LM) using simple staining techniques. [19] Pit area can be quantified using image analysis software applied to SEM or LM. Ideally, pit volume would be the best method when quantifying resorption as both pit area and depth can be calculated; however, the required equipment is expensive and specialized. [20-23] All of these methods are time consuming, labor intensive, and,
Our populations are aging. Some experts predict that 30% of hospital beds will soon be occupied b... more Our populations are aging. Some experts predict that 30% of hospital beds will soon be occupied by osteoporosis patients. Statistics show that 20% of patients suffering from an osteoporotic hip fracture do not survive the first year after surgery, all this showing that there is a tremendous need for better therapies for diseased and damaged bone. Human bone consists for about 70% of calcium phosphate (CaP) mineral, therefore CaPs are the materials of choice to repair damaged bone. To do this successfully, the process of CaP biomineralization and the interaction of CaPs and biological environment in the body need to be fully understood. First commercial CaP bone graft substitutes were launched 40 years ago, and they are currently often regarded as 'old biomaterials' or even as an 'obsolete' research topic. Some even talk about 'stones'. The aim of this manuscript is to highlight the tremendous improvements achieved in CaP materials research in the past 15 years, in particular in the field of biomineralization, as carrier for gene or ion delivery, as biologically active agent, and as bone graft substitute. Besides an outstanding biological performance, CaPs are easily and inexpensively produced, are safe, and can be relatively easily certified for clinical use. As such, CaP materials have won their spurs, but they also offer a great promise for the future.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
In vitro measurement of the chemical changes occurring within β-tricalcium phosphate bone graft s... more In vitro measurement of the chemical changes occurring within β-tricalcium phosphate bone graft substitutes,
Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2017
This study introduced and demonstrated a new method to investigate the repair process of bone def... more This study introduced and demonstrated a new method to investigate the repair process of bone defects using micro-and macroporous beta-tricalcium phosphate (b-TCP) substitutes. Specifically, the new method combined and aligned histology, SEM, and preimplantation microcomputed tomography (mCT) data to accurately characterize tissue phases found in biopsies, and thus better understand the bone repair process. The results included (a) the exact fraction of ceramic remnants (CR); (b) the fraction of ceramic resorbed and substituted by bone (CSB); and (c) the fraction of ceramic resorbed and not substituted by bone (CNSB). The new method allowed in particular the detection and quantification of mineralized tissues within the 1-10 mm micropores of the ceramic ("micro-bone"). The utility of the new method was demonstrated by applying it on biopsies of two b-tricalcium phosphate bone substitute groups with two differing macropore sizes implanted in an ovine model for 6 weeks. The total bone deposition and ceramic resorption of the two substitute groups, having macropore sizes of 510 and 1220 lm, were 25.1 6 8.1% and 67.5 6 3.2%, and 24.4 6 4.1% and 61.4 6 6.5% for the group having the larger pore size. V
Objective: The aim of this study was to produce a novel composite of microporous β-TCP filled wit... more Objective: The aim of this study was to produce a novel composite of microporous β-TCP filled with alginate and Vancomycin (VAN) to prolong the release behavior of the antibiotic for up to 28 days. Material and Methods: Using the flow chamber developed by the group, porous ceramics in a directional flow were filled with alginates of different composition containing 50 mg/mL of antibiotics. After cross-linking the alginate with calcium ions, incubation took place in 10 mL double-distilled water for 4 weeks at 37 °C. At defined times (1, 2, 3, 6, 9, 14, 20 and 28 days), the liquid was completely exchanged and analyzed by capillary zone electrophoresis and microtiter trials. For statistical purposes, the mean and standard deviation were calculated and analyzed by ANOVA. Results: The release of VAN from alginate was carried out via an external calcium source over the entire period with concentrations above the minimal inhibitory concentration (MIC). The burst release measured 35.2 ± 1.5%. The release of VAN from alginate with an internal calcium source could only be observed over 14 days. The burst release here was 61.9 ± 4.3%. The native alginate's burst release was 54.1 ± 7.8%; that of the sterile alginate 40.5 ± 6.4%. The microtiter experiments revealed efficacy over the entire study period for VAN. The MIC value was determined in the release experiments as well in a range of 0.5-2.0 µg/mL against Staphylococcus aureus.
Various compositions of synthetic calcium phosphates (CaP) have been proposed and their use has c... more Various compositions of synthetic calcium phosphates (CaP) have been proposed and their use has considerably increased over the past decades. Besides differences in physicochemical properties, resorption and osseointegration, artificial CaP bone graft might differ in their resistance against biofilm formation. We investigated standardised cylinders of 5 different CaP bone grafts (cyclOS, chronOS (both β-TCP (tricalcium phosphate)), dicalcium phosphate (DCP), calcium-deficient hydroxyapatite (CDHA) and α-TCP). Various physico-chemical characterisations e.g., geometrical density, porosity, and specific surface area were investigated. Biofilm formation was carried out in tryptic soy broth (TSB) and human serum (SE) using Staphylococcus aureus (ATCC 29213) and S. epidermidis RP62A (ATCC 35984). The amount of biofilm was analysed by an established protocol using sonication and microcalorimetry. Physico-chemical characterisation showed marked differences concerning macro-and micropore size, specific surface area and porosity accessible to bacteria between the 5 scaffolds. Biofilm formation was found on all scaffolds and was comparable for α-TCP, chronOS, CDHA and DCP at corresponding time points when the scaffolds were incubated with the same germ and/or growth media, but much lower for cyclOS. This is peculiar because cyclOS had an intermediate porosity, mean pore size, specific surface area, and porosity accessible to bacteria. Our results suggest that biofilm formation is not influenced by a single physico-chemical parameter alone but is a multi-step process influenced by several factors in parallel. Transfer from in vitro data to clinical situations is difficult; thus, advocating the use of cyclOS scaffolds over the four other CaP bone grafts in clinical situations with a high risk of infection cannot be clearly supported based on our data.
Micro-computed tomography (microCT) is commonly used to characterize the three-dimensional struct... more Micro-computed tomography (microCT) is commonly used to characterize the three-dimensional structure of bone graft scaffolds before and after implantation in order to assess changes occurring during implantation. The accurate processing of the microCT datasets of explanted β-tricalcium phosphate (β-TCP) scaffolds poses significant challenges because of (a) the overlap in the grey values distribution of ceramic remnants, bone, and soft tissue, and of (b) the resorption of the bone substitute during the implantation. To address those challenges, this article introduces and rigorously validates a new processing technique to accurately distinguish these three phases found in the explanted β-TCP scaffolds. Specifically, the microCT datasets obtained before and after implantation of β-TCP scaffolds were aligned in 3D, and the characteristic grey value distributions of the three phases were extracted, thus allowing for (i) the accurate differentiation between these three phases (ceramic re...
β-Tricalcium phosphate (β-TCP) platelets synthesized in ethylene glycol offer interesting geometr... more β-Tricalcium phosphate (β-TCP) platelets synthesized in ethylene glycol offer interesting geometries for nano-structured composite bone substitutes but were never crystallographically analyzed. In this study, powder X-ray diffraction and Rietveld refinement revealed a discrepancy between the platelet structure and the known β-TCP crystal model. In contrast, a model featuring partial H for Ca substitution and the inversion of P1O4 tetrahedra, adopted from the whitlockite structure, allowed for a refinement with minimal misfits and was corroborated by HPO4(2-) absorptions in Fourier-transform IR spectra. The Ca/P ratio converged to 1.443 ± 0.003 (n = 36), independently of synthesis conditions. As a quantitative verification, the platelets were thermally decomposed into hydrogen-free β-TCP and β-calcium pyrophosphate which resulted in a global Ca/P ratio in close agreement with the initial β-TCP Ca/P ratio (ΔCa/P = 0.003) and with the chemical composition measured by inductively couple...
Little is known regarding the associations between sex-hormone levels, sex, body mass index (BMI)... more Little is known regarding the associations between sex-hormone levels, sex, body mass index (BMI), age, other host factors and biomaterial stimulated bone regeneration in the human craniofacial skeleton. The aim of this study was to elucidate the associations between these factors and bone formation after sinus floor augmentation procedures (SFA) utilizing a bioactive tricalcium phosphate (TCP) bone grafting material. We conducted a prospective study in a human population in which 60 male and 60 female participants underwent SFA and dental implant placement using a staged approach. BMI as well as levels of serum estradiol (E2), total testosterone (TT), and the free androgen index (FAI) were measured by radioimmunoassay and electrochemoluminescent-immunoassay. At implant placement, 6 months after SFA, bone biopsy specimens were harvested for hard tissue histology, the amount of bone formation was evaluated by histomorphometry and immunohistochemical analysis of osteogenic marker expression. The Wilcoxon rank-sum U test, Spearman correlations and linear regression analysis were used to explore the association between bone formation and BMI, hormonal and other host factors. BMI and log E2 were significantly positively associated with bone formation in male individuals (p < 0.05). Histomorphometry revealed trends toward greater bone formation and osteogenic marker expression with non-smokers compared to smokers. In male patients, higher E2 levels and higher BMI enhanced TCP stimulated craniofacial i.e. intramembranous bone repair.
NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteo... more NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteochondral cells. It was widely used in bone regeneration research by loading onto carriers such as tricalcium phosphate (TCP) particles. However, there has been little research on protein controlled release from this material and its potential application. In this study, TCP was first modified with a hydroxyapatite coating followed by a chitosan coating to prepare chitosan/hydroxyapatite-coated TCP particles (Chi/HA-TCP). The preparation was characterized by SEM, EDX, FTIR, XRD, FM and Zeta potential measurements. The NELL-1 loaded Chi/HA-TCP particles and the release kinetics were investigated in vitro. It was observed that the Chi/HA-TCP particles prepared with the 0.3% (wt/wt) chitosan solution were able to successfully control the release of NELL-1 and maintain a slow, steady release for up to 28 days. Furthermore, more than 78% of the loaded protein's bioactivity was preserved in Chi/HA-TCP particles over the period of the investigation, which was significantly higher than that of the protein released from hydroxyapatite coated TCP (HA-TCP) particles. Collectively, this study suggests that the osteogenic protein NELL-1 showed a sustained release pattern after being encapsulated into the modified Chi/HA-TCP particles, and the NELL-1 integrated composite of Chi/HA-TCP showed a potential to function as a protein delivery carrier and as an improved bone matrix for use in bone regeneration research. 2016 Elsevier B.V. All rights reserved.
Frontiers in Bioengineering and Biotechnology, 2016
most likely treatment option, often in conjunction with a bone graft to stimulate healing. [1] Bo... more most likely treatment option, often in conjunction with a bone graft to stimulate healing. [1] Bone grafting using autologous or allograft bone is the "gold standard" but there are associated limitations; a second surgical procedure with related donor-site morbidity, concerns of immunogenicity, and demand outweighing supply. [2-4] This has led to a demand for synthetic bone grafts but to date commercially available synthetic grafts have been unable to match the clinical results seen with autograft. [2,5] Ideally synthetic bone grafts should be biocompatible, integrate with the bone resorption process, and aid new bone ingrowth while retaining sufficient mechanical strength. Resorbable materials that can utilize the bone's natural remodeling process to degrade, releasing nontoxic by-products that can be easily metabolized by the body, are very attractive for use as bone graft substitutes. However, some alleged resorbable bone graft substitutes have been detected years after in vivo implantation. [6,7] Innovation of porous scaffolds with an interconnected pore structure has allowed for increased bone ingrowth [8-11] and subsequent increased rate of resorption in vivo. [12-15] The introduction of porosity has caused a new challenge for researchers when measuring bioresorption of new materials, rendering the traditional in vitro methods insufficient. The traditional methods used to assess resorbability of bone substitutes in vitro are osteoclast (OC) formation indicated by tartrateresistant acid phosphatase (TRAP) expression and a cell-based resorption assay, alternatively known as a "pit" assay, developed by Boyde et al. [16] and Chambers et al. [17] Initially developed as an assay to investigate OC biology using dentine or bone as a substrate, it is now routinely used to understand biomaterial resorption. OCs are cultured on biomaterial surfaces for specific periods and then detached, at which point the excavated areas (pits) beneath the cells can be analyzed by scanning electron microscopy (SEM) in terms of pit number, pit area, or pit volume. The simplest method is to determine the number of pits, which can be quantified using reflected light microscopy, where staining is not required, [18] or by light microscopy (LM) using simple staining techniques. [19] Pit area can be quantified using image analysis software applied to SEM or LM. Ideally, pit volume would be the best method when quantifying resorption as both pit area and depth can be calculated; however, the required equipment is expensive and specialized. [20-23] All of these methods are time consuming, labor intensive, and,
Our populations are aging. Some experts predict that 30% of hospital beds will soon be occupied b... more Our populations are aging. Some experts predict that 30% of hospital beds will soon be occupied by osteoporosis patients. Statistics show that 20% of patients suffering from an osteoporotic hip fracture do not survive the first year after surgery, all this showing that there is a tremendous need for better therapies for diseased and damaged bone. Human bone consists for about 70% of calcium phosphate (CaP) mineral, therefore CaPs are the materials of choice to repair damaged bone. To do this successfully, the process of CaP biomineralization and the interaction of CaPs and biological environment in the body need to be fully understood. First commercial CaP bone graft substitutes were launched 40 years ago, and they are currently often regarded as 'old biomaterials' or even as an 'obsolete' research topic. Some even talk about 'stones'. The aim of this manuscript is to highlight the tremendous improvements achieved in CaP materials research in the past 15 years, in particular in the field of biomineralization, as carrier for gene or ion delivery, as biologically active agent, and as bone graft substitute. Besides an outstanding biological performance, CaPs are easily and inexpensively produced, are safe, and can be relatively easily certified for clinical use. As such, CaP materials have won their spurs, but they also offer a great promise for the future.
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