Abstract:Aiming at the generation of a high strontium‐containing degradable bone substitute, the exchange of calcium with strontium in gelatin‐modified brushite was investigated. The ion substitution showed two mineral groups, the high‐calcium containing minerals with a maximum measured molar Ca/Sr ratio of 80%/20% (mass ratio 63%/37%) and the high‐strontium containing ones with a maximum measured molar Ca/Sr ratio of 21%/79% (mass ratio 10%/90%). In contrast to the high‐strontium mineral phases, a high mass loss was o… Show more
“…At the same time, material degradation took place, which was reflected by the decrease of the indirect tensile strength of the specimens. This was in line with the observations previously made for this class of materials, ranging from strontium-free PPGC + S 10:0 to calcium-free PPGC + S 0:10 [12,13], upon which the selection of materials for co-culture and animal testing was based. With PPGC + S 5:5, the following effect occurred during incubation in the cell culture medium.…”
Section: Discussionsupporting
confidence: 89%
“…The initial ratio of the calcium/strontium ions can be used to vary the mineral morphology, structure, and degradability [12]. Especially, the specimen of phosphate-prestructured gelatin mineralized with mixed solutions of calcium:strontium 5:5 (short PPGC + S 5:5) and specimen of PPGC + S 3:7 turned out to be particularly promising for further investigations [13]. As a brief introduction, PPGC + S 5:5 on the one hand is calcium phosphate, brushite with disturbed morphology and crystal structure by strontium substitution with a measured Ca/Sr-ratio of 63%/37% by mass.…”
Section: Introductionmentioning
confidence: 99%
“…Osteoblasts showed good adhesion, proliferation, and differentiation in mono-culture, while human mononuclear cells (hMc) showed fusion to osteoclasts and resorption activity, proven by connexion 43 and 37 as well as tartrate-resistant acid phosphatase isoenzyme 5b (TRAP) activity [12]. PPGC + S 3:7 is less bioactive and, therefore, only an initial increase in cation concentration was present during incubation and no hardening was observed [13]. The osteoblasts showed good adhesion, proliferation, and increased and faster differentiation.…”
The development and characterization of biomaterials for bone replacement in case of large defects in preconditioned bone (e.g., osteoporosis) require close cooperation of various disciplines. Of particular interest are effects observed in vitro at the cellular level and their in vivo representation in animal experiments. In the present case, the material-based alteration of the ratio of osteoblasts to osteoclasts in vitro in the context of their co-cultivation was examined and showed equivalence to the material-based stimulation of bone regeneration in a bone defect of osteoporotic rats. Gelatin-modified calcium/strontium phosphates with a Ca:Sr ratio in their precipitation solutions of 5:5 and 3:7 caused a pro-osteogenic reaction on both levels in vitro and in vivo. Stimulation of osteoblasts and inhibition of osteoclast activity were proven during culture on materials with higher strontium content. The same material caused a decrease in osteoclast activity in vitro. In vivo, a positive effect of the material with increased strontium content was observed by immunohistochemistry, e.g., by significantly increased bone volume to tissue volume ratio, increased bone morphogenetic protein-2 (BMP2) expression, and significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio. In addition, material degradation and bone regeneration were examined after 6 weeks using stage scans with ToF-SIMS and µ-CT imaging. The remaining material in the defects and strontium signals, which originate from areas exceeding the defect area, indicate the incorporation of strontium ions into the surrounding mineralized tissue. Thus, the material inherent properties (release of biologically active ions, solubility and degradability, mechanical strength) directly influenced the cellular reaction in vitro and also bone regeneration in vivo. Based on this, in the future, materials might be synthesized and specifically adapted to patient-specific needs and their bone status.
“…At the same time, material degradation took place, which was reflected by the decrease of the indirect tensile strength of the specimens. This was in line with the observations previously made for this class of materials, ranging from strontium-free PPGC + S 10:0 to calcium-free PPGC + S 0:10 [12,13], upon which the selection of materials for co-culture and animal testing was based. With PPGC + S 5:5, the following effect occurred during incubation in the cell culture medium.…”
Section: Discussionsupporting
confidence: 89%
“…The initial ratio of the calcium/strontium ions can be used to vary the mineral morphology, structure, and degradability [12]. Especially, the specimen of phosphate-prestructured gelatin mineralized with mixed solutions of calcium:strontium 5:5 (short PPGC + S 5:5) and specimen of PPGC + S 3:7 turned out to be particularly promising for further investigations [13]. As a brief introduction, PPGC + S 5:5 on the one hand is calcium phosphate, brushite with disturbed morphology and crystal structure by strontium substitution with a measured Ca/Sr-ratio of 63%/37% by mass.…”
Section: Introductionmentioning
confidence: 99%
“…Osteoblasts showed good adhesion, proliferation, and differentiation in mono-culture, while human mononuclear cells (hMc) showed fusion to osteoclasts and resorption activity, proven by connexion 43 and 37 as well as tartrate-resistant acid phosphatase isoenzyme 5b (TRAP) activity [12]. PPGC + S 3:7 is less bioactive and, therefore, only an initial increase in cation concentration was present during incubation and no hardening was observed [13]. The osteoblasts showed good adhesion, proliferation, and increased and faster differentiation.…”
The development and characterization of biomaterials for bone replacement in case of large defects in preconditioned bone (e.g., osteoporosis) require close cooperation of various disciplines. Of particular interest are effects observed in vitro at the cellular level and their in vivo representation in animal experiments. In the present case, the material-based alteration of the ratio of osteoblasts to osteoclasts in vitro in the context of their co-cultivation was examined and showed equivalence to the material-based stimulation of bone regeneration in a bone defect of osteoporotic rats. Gelatin-modified calcium/strontium phosphates with a Ca:Sr ratio in their precipitation solutions of 5:5 and 3:7 caused a pro-osteogenic reaction on both levels in vitro and in vivo. Stimulation of osteoblasts and inhibition of osteoclast activity were proven during culture on materials with higher strontium content. The same material caused a decrease in osteoclast activity in vitro. In vivo, a positive effect of the material with increased strontium content was observed by immunohistochemistry, e.g., by significantly increased bone volume to tissue volume ratio, increased bone morphogenetic protein-2 (BMP2) expression, and significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio. In addition, material degradation and bone regeneration were examined after 6 weeks using stage scans with ToF-SIMS and µ-CT imaging. The remaining material in the defects and strontium signals, which originate from areas exceeding the defect area, indicate the incorporation of strontium ions into the surrounding mineralized tissue. Thus, the material inherent properties (release of biologically active ions, solubility and degradability, mechanical strength) directly influenced the cellular reaction in vitro and also bone regeneration in vivo. Based on this, in the future, materials might be synthesized and specifically adapted to patient-specific needs and their bone status.
“…These platy crystals were very thin (~200 nm), but their width and elongation were ~10 μm and 20 μm, respectively (Tadier et al , 2012). The platy morphology is typical of precipitated brushite (Schmacher & Gelinsky, 2015; Kruppke et al , 2020). Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Brushite is an important precursor of several bone cements and bioceramics (Alshaaer et al, 2013(Alshaaer et al, , 2017. The novelty of this research lies in the study of the effects of the full-scale replacement of Ca by Sr as one of the most important elements in biomaterials (Kruppke et al, 2020) starting from pure brushite. The 'replacement' in this study is defined as the substitution of Ca by Sr and maintaining the same conditions during the powder preparation.…”
Brushite (CaHPO4.2H2O) is an important calcium phosphate encountered in bone tissue engineering and bone cement formulation. There are many studies on the synthesis and characterization of brushite, but full-scale substitution and replacement of Ca by Sr in brushite as a key element in medical and environmental applications has not yet been explored systematically. Therefore, this study aims to evaluate the effects of substitution of Ca by Sr on the microstructural and thermal properties of brushite, including the chemical phases present, crystallization, structural water and phase stability. The chemical phases were determined by means of powder X-ray diffraction. The thermal properties were studied by thermogravimetric analysis. Crystallization and surface morphology were analysed using scanning electron microscopy. Various properties were dependent on the incorporated Sr ions. The replacement percentage of Sr may be divided into two major stages: the first from 0% to 50%; and the second from 50% up to 100%. The (Ca
x
Sr1–x)HPO4.nH2O shows that micro-scale crystals of platy brushite formed in the first stage of Sr replacement, from 0% up to 50%. As Sr might inhibit the formation of crystals, crystal nucleation rates were reduced as the Sr percentage increased. An amorphous product formed as a result of 50% Sr replacement. The second stage of Sr replacement with Sr contents >50% yielded a new crystal morphology corresponding mainly to SrHPO4.nH2O. The complete replacement of Ca by Sr transforms the brushite with platy microcrystals into SrHPO4 nanosheets.
Calcium phosphate nanoparticles are highly biocompatible and biodegradable in bone regeneration. On the other hand, strontium and magnesium enhance the formation of bone. The substitution of calcium by strontium and magnesium is an efficient way to improve the biological properties of calcium phosphate-based biomaterials. Strontium-doped calcium phosphate nanoparticles and magnesium-doped calcium phosphate nanoparticles with degrees of cation substitution of 5, 10, 15, and 20 mol% with respect to calcium were prepared by precipitation, followed by surface functionalization with polyethyleneimine (PEI, cationic) or carboxymethylcellulose (CMC, anionic). The nanoparticles were characterized by dynamic light scattering (DLS), zeta potential measurement, scanning electron microscopy (SEM), atomic absorption spectrometry (AAS), energy dispersive X-ray analysis (EDX), and X-ray powder diffraction (XRD). The particles were approximately spherical (diameter 40–70 nm). The addition of magnesium and strontium considerably decreased the internal crystallinity, i.e., the doped particles were almost X-ray amorphous. The cell-biological effects were assessed on three different cell lines, i.e., HeLa cells, MG63 cells, and MC3T3 cells. Cell viability tests (MTT) showed a low cytotoxicity, the alkaline phosphatase (ALP) activity was strongly increased, and the nanoparticles were taken up well by the three cell lines.
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