Phosphoserine Functionalized Cements Preserve Metastable Phases, and Reprecipitate Octacalcium Phosphate, Hydroxyapatite, Dicalcium Phosphate, and Amorphous Calcium Phosphate, during Degradation, In Vitro

Phosphoserine modified cements (PMC) exhibit unique properties, including strong adhesion to tissues and biomaterials. While TTCP-PMCs remodel into bone in vivo, little is known regarding the bioactivity and physiochemical changes that occur during resorption. In the present study, changes in the mechanical strength and composition were evaluated for 28 days, for three formulations of αTCP based PMCs. PMCs were significantly stronger than unmodified cement (38–49 MPa vs. 10 MPa). Inclusion of wollastonite in PMCs appeared to accelerate the conversion to hydroxyapatite, coincident with slight decrease in strength. In non-wollastonite PMCs the initial compressive strength did not change after 28 days in PBS (p > 0.99). Dissolution/degradation of PMC was evaluated in acidic (pH 2.7, pH 4.0), and supersaturated fluids (simulated body fluid (SBF)). PMCs exhibited comparable mass loss (<15%) after 14 days, regardless of pH and ionic concentration. Electron microscopy, infrared spectroscopy, and X-ray analysis revealed that significant amounts of brushite, octacalcium phosphate, and hydroxyapatite reprecipitated, following dissolution in acidic conditions (pH 2.7), while amorphous calcium phosphate formed in SBF. In conclusion, PMC surfaces remodel into metastable precursors to hydroxyapatite, in both acidic and neutral environments. By tuning the composition of PMCs, durable strength in fluids, and rapid transformation can be obtained.

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The Role of Brushite and Octacalcium Phosphate in Apatite Formation

Critical Reviews in Oral Biology & Medicine ◽

10.1177/10454411920030010601 ◽

1992 ◽

Vol 3 (1) ◽

pp. 61-82 ◽

Cited By ~ 224

Author(s):

Mats S.-A. Johnsson ◽

George H. Nancollas

Keyword(s):

Calcium Phosphate ◽

Octacalcium Phosphate ◽

In Vivo Studies ◽

Apatite Formation ◽

Acidic Solutions ◽

Phosphate Phase ◽

Apatite Mineral

Studies of apatite mineral formation are complicated by the possibility of forming several calcium phosphate phases. The least soluble, hydroxyapatite (HAP), is preferentially formed under neutral or basic conditions. In more acidic solutions phases such as dicalcium phosphate dihydrate (Brushite, DCPD) and octacalcium phosphate (OCP) are often found. Even under ideal HAP precipitation conditions the precipitates are generally nonstoichiometric, suggesting the formation of calcium-deficient apatites. Both DCPD and OCP havea been implicated as possible precursors to the formation of apatite. This may occur by the initial precipitation of DCPD and/or OCP followed by transformation to a more apatitic phase. Although DCPD and OCP are often detected during in vitro crystallization, in vivo studies of bone formation rarely show the presence of these acidic calcium phosphate phases. In the latter case the situation is more complicated, since a large number of ions and molecules are present that can be incorporated into the crystal lattice or adsorbed at the crystallite surfaces. In biological apatite, DCPD and OCP are usually detected only during pathological calcification where the pH is often relatively low. In normal in vivo calcifications these phases have not been found, suggesting the involvement of other precursors or the formation of an initial amorphous calcium phosphate phase (ACP) followed by transformation to apatite.

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In vitro and in vivo degradation of poly(D, L-lactide-co-glycolide)/amorphous calcium phosphate copolymer coated on metal stents

Journal of Biomedical Materials Research Part A ◽

10.1002/jbm.a.33016 ◽

2011 ◽

Vol 96A (4) ◽

pp. 632-638 ◽

Cited By ~ 13

Author(s):

Xiaodong Ma ◽

Shizu Oyamada ◽

Tim Wu ◽

Michael P. Robich ◽

Hao Wu ◽

...

Keyword(s):

Calcium Phosphate ◽

Amorphous Calcium Phosphate ◽

Metal Stents ◽

In Vivo Degradation

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In vitro and in vivo evaluation of electrophoresis-aided casein phosphopeptide-amorphous calcium phosphate remineralisation system on pH-cycling and acid-etching demineralised enamel

Scientific Reports ◽

10.1038/s41598-018-27304-5 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 4

Author(s):

Yu Yuan Zhang ◽

Hai Ming Wong ◽

Colman P. J. McGrath ◽

Quan Li Li

Keyword(s):

Calcium Phosphate ◽

Amorphous Calcium Phosphate ◽

Acid Etching ◽

In Vivo Evaluation ◽

Ph Cycling ◽

Casein Phosphopeptide

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Amorphous calcium phosphate nanoparticles using adenosine triphosphate as an organic phosphorus source for promoting tendon–bone healing

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01007-y ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Haoran Liao ◽

Han-Ping Yu ◽

Wei Song ◽

Guangcheng Zhang ◽

Bingqiang Lu ◽

...

Keyword(s):

Calcium Phosphate ◽

Rotator Cuff ◽

Adenosine Triphosphate ◽

Bone Healing ◽

Amorphous Calcium Phosphate ◽

Organic Phosphorus ◽

Biological Activities ◽

Phosphorus Source

Abstract Background Rotator cuff tear (RCT) is a common problem of the musculoskeletal system. With the advantage of promoting bone formation, calcium phosphate materials have been widely used to augment tendon-bone healing. However, only enhancing bone regeneration may be not enough for improving tendon–bone healing. Angiogenesis is another fundamental factor required for tendon–bone healing. Therefore, it’s necessary to develop a convenient and reliable method to promote osteogenesis and angiogenesis simultaneously, thereby effectively promoting tendon–bone healing. Methods The amorphous calcium phosphate (ACP) nanoparticles with dual biological activities of osteogenesis and angiogenesis were prepared by a simple low-temperature aqueous solution method using adenosine triphosphate (ATP) as an organic phosphorus source. The activities of osteogenesis and angiogenesis and the effect on the tendon–bone healing of ACP nanoparticles were tested in vitro and in a rat model of acute RCT. Results The ACP nanoparticles with a diameter of tens of nanometers were rich in bioactive adenosine. In vitro, we confirmed that ACP nanoparticles could enhance osteogenesis and angiogenesis. In vivo, radiological and histological evaluations demonstrated that ACP nanoparticles could enhance bone and blood vessels formation at the tendon–bone junction. Biomechanical testing showed that ACP nanoparticles improved the biomechanical strength of the tendon–bone junction and ultimately promoted tendon–bone healing of rotator cuff. Conclusions We successfully confirmed that ACP nanoparticles could promote tendon–bone healing. ACP nanoparticles are a promising biological nanomaterial in augmenting tendon–bone healing. Graphic abstract

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Biomimetic Organic-Inorganic Nanocomposite Coatings for Titanium Implants. II. Biological "In Vitro" and "In Vivo" Characterization

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.330-332.401 ◽

2007 ◽

Vol 330-332 ◽

pp. 401-404 ◽

Cited By ~ 3

Author(s):

M. Dutour Sikirić ◽

Rene Elkaim ◽

S. Lamolle ◽

H.J. Ronold ◽

S.P. Lyngstadass ◽

...

Keyword(s):

Calcium Phosphate ◽

Amorphous Calcium Phosphate ◽

Organic Matrix ◽

Titanium Implants ◽

Nanocomposite Coatings ◽

In Vivo Testing ◽

In Vivo Characterization

Biological mineralization proceeds within an organic matrix and is induced and controlled by extracellular, highly acidic matrix macromolecules. Our group has recently prepared organic-inorganic nanocomposite coatings by a strategy that closely mimics these processes. The strategy involves depositing a matrix of polyelectrolyte multilayers (PE MLs), alternating with layers of amorphous calcium phosphate (ACP) particles, then "in situ" growing nanosized apatite crystals within that matrix [1, 2]. Here we describe the results of biological "in vitro" and "in vivo" testing of these materials.

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Ultra-strong bio-glue from genetically engineered polypeptides

Nature Communications ◽

10.1038/s41467-021-23117-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Chao Ma ◽

Jing Sun ◽

Bo Li ◽

Yang Feng ◽

Yao Sun ◽

...

Keyword(s):

Soft Tissues ◽

Covalent Bond ◽

Genetically Engineered ◽

Supramolecular Interactions ◽

Molar Ratio ◽

High Adhesion ◽

Strong Adhesion ◽

Order Of Magnitude

AbstractThe development of biomedical glues is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, i.e. strong adhesion and adaption to remodeling processes in healing tissue. Here, we report a biocompatible and biodegradable protein-based adhesive with high adhesion strengths. The maximum strength reaches 16.5 ± 2.2 MPa on hard substrates, which is comparable to that of commercial cyanoacrylate superglue and higher than other protein-based adhesives by at least one order of magnitude. Moreover, the strong adhesion on soft tissues qualifies the adhesive as biomedical glue outperforming some commercial products. Robust mechanical properties are realized without covalent bond formation during the adhesion process. A complex consisting of cationic supercharged polypeptides and anionic aromatic surfactants with lysine to surfactant molar ratio of 1:0.9 is driven by multiple supramolecular interactions enabling such strong adhesion. We demonstrate the glue’s robust performance in vitro and in vivo for cosmetic and hemostasis applications and accelerated wound healing by comparison to surgical wound closures.

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Doxorubicin loaded magnetism nanoparticles based on cyclodextrin dendritic-graphene oxide inhibited MCF-7 cell proliferation

BioMolecular Concepts ◽

10.1515/bmc-2021-0002 ◽

2021 ◽

Vol 12 (1) ◽

pp. 8-15

Author(s):

Ainaz Mihanfar ◽

Niloufar Targhazeh ◽

Shirin Sadighparvar ◽

Saber Ghazizadeh Darband ◽

Maryam Majidinia ◽

...

Keyword(s):

Graphene Oxide ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Anticancer Drug Delivery ◽

Release Studies ◽

Anti Cancer ◽

Acidic Conditions ◽

Mcf 7

Abstract Doxorubicin (DOX) is an effective chemotherapeutic agent used for the treatment of various types of cancer. However, its poor solubility, undesirable side effects, and short half-life have remained a challenge. We used a formulation based on graphene oxide as an anticancer drug delivery system for DOX in MCF-7 breast cancer cells, to address these issues. In vitro release studies confirmed that the synthesized formulation has an improved release profile in acidic conditions (similar to the tumor microenvironment). Further in vitro studies, including MTT, uptake, and apoptosis assays were performed. The toxic effects of the nanocarrier on the kidney, heart and liver of healthy rats were also evaluated. We observed that the DOX-loaded carrier improved the cytotoxic effect of DOX on the breast cell line compared to free DOX. In summary, our results introduce the DOX-loaded carrier as a potential platform for in vitro targeting of cancer cells and suggest further studies are necessary to investigate its in vivo anti-cancer potential.

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Cemp1-p3 Peptide Promotes the Transformation of Octacalcium Phosphate into Hydroxyapatite Crystals

Crystals ◽

10.3390/cryst10121131 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1131

Author(s):

Maricela Santana ◽

Gonzalo Montoya ◽

Raúl Herrera ◽

Lía Hoz ◽

Enrique Romo ◽

...

Keyword(s):

Electron Microscopy ◽

Octacalcium Phosphate ◽

Sequence Motifs ◽

Simple Method ◽

Transmission Electron ◽

Precursor Phase ◽

Mineralized Tissues ◽

Potent Growth

Dental cementum contains unique molecules that regulate the mineralization process in vitro and in vivo, such as cementum protein 1 (CEMP1). This protein possesses amino acid sequence motifs like the human recombinant CEMP1 with biological activity. This novel cementum protein 1-derived peptide (CEMP1-p3, from the CEMP1’s N-terminal domain: (QPLPKGCAAVKAEVGIPAPH), consists of 20 amino acids. Hydroxyapatite (HA) crystals could be obtained through the combination of the amorphous precursor phase and macromolecules such as proteins and peptides. We used a simple method to synthesize peptide/hydroxyapatite nanocomposites using OCP and CEMP1-p3. The characterization of the crystals through scanning electron microscopy (SEM), powder X-ray diffraction (XRD), high--resolution transmission electron microscopy (HRTEM), and Raman spectroscopy revealed that CEMP1-p3 transformed OCP into hydroxyapatite (HA) under constant ionic strength and in a buffered solution. CEMP1-p3 binds and highly adsorbs to OCP and is a potent growth stimulator of OCP crystals. CEMP1-p3 fosters the transformation of OCP into HA crystals with crystalline planes (300) and (004) that correspond to the cell of hexagonal HA. Octacalcium phosphate crystals treated with CEMP1-p3 grown in simulated physiological buffer acquired hexagonal arrangement corresponding to HA. These findings provide new insights into the potential application of CEMP1-p3 on possible biomimetic approaches to generate materials for the repair and regeneration of mineralized tissues, or restorative materials in the orthopedic field.

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