Application of an indicator-immobilized-gel-sheet for measuring the pH surrounding a calcium phosphate-based biomaterial

The present study was designed to investigate the local microenvironment of octacalcium phosphate in a granule form upon biomolecules adsorption utilizing an indicator-immobilized-gel-sheet for measuring pH. We previously showed that octacalcium phosphate enhances bone regeneration during its progressive hydrolysis into hydroxyapatite if implanted in bone defects. The gel-sheet was made from a photocrosslinkable prepolymer solution, which can easily immobilize a pH indicator (bromothymol blue; BTB) in the hydrogel. The indicator-immobilized-gel-sheet was mounted on a biochip which was made of polydimethylsiloxane (PDMS) with a flow channel. The pH value was calculated by detecting the color changes in the gel-sheet and displayed as the pH distribution. After pre-adsorption of bovine albumin, β-lactoglobuline or cytochrome C onto octacalcium phosphate granules, the granules with the gel-sheet were further incubated in Tris-HCl buffer solution in the absence or presence of fluoride, known as an accelerator of octacalcium phosphate hydrolysis. pH values of the gel-sheet surrounding octacalcium phosphate granules showed a decrease from pH 7.4 to 6.6 in relation to the proteins adsorbed. Overall, the proposed pH-sensitive gel can be used to detect the pH around octacalcium phosphate granules with a high spatial resolution.

[1]  Y. Shikinami,et al.  Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly-L-lactide (PLLA): Part I. Basic characteristics. , 1999, Biomaterials.

[2]  Fumihito Arai,et al.  On-chip pH measurement using functionalized gel-microbeads positioned by optical tweezers. , 2008, Lab on a chip.

[3]  Jill P. G. Urban,et al.  The effect of extracellular pH on matrix turnover by cells of the bovine nucleus pulposus , 2003, European Spine Journal.

[4]  O. Suzuki,et al.  Surface chemistry and biological responses to synthetic octacalcium phosphate. , 2006, Journal of biomedical materials research. Part B, Applied biomaterials.

[5]  H. Mckenzie,et al.  Effect of pH on β-Lactoglobulins , 1967, Nature.

[6]  M. A. Rothschild,et al.  Serum albumin , 2005, The American Journal of Digestive Diseases.

[7]  Takashi Nakamura,et al.  Process and kinetics of bonelike apatite formation on sintered hydroxyapatite in a simulated body fluid. , 2005, Biomaterials.

[8]  R. Kamijo,et al.  Bone formation enhanced by implanted octacalcium phosphate involving conversion into Ca-deficient hydroxyapatite. , 2006, Biomaterials.

[9]  A. Ogose,et al.  Histological assessment in grafts of highly purified beta-tricalcium phosphate (OSferion) in human bones. , 2006, Biomaterials.

[10]  R. Kamijo,et al.  Synthetic octacalcium phosphate‐enhanced reparative dentine formation via induction of odontoblast differentiation , 2015, Journal of tissue engineering and regenerative medicine.

[11]  Y. Miyamoto,et al.  Osteoclast differentiation induced by synthetic octacalcium phosphate through receptor activator of NF-kappaB ligand expression in osteoblasts. , 2009, Tissue engineering. Part A.

[12]  E. Moreno,et al.  Fluoridated Hydroxyapatite Solubility and Caries Formation , 1974, Nature.

[13]  T. Anada,et al.  Structural, morphological and surface characteristics of two types of octacalcium phosphate-derived fluoride-containing apatitic calcium phosphates. , 2012, Acta biomaterialia.

[14]  A. W. Frazier,et al.  Octacalcium Phosphate and Hydroxyapatite: Crystallographic and Chemical Relations between Octacalcium Phosphate and Hydroxyapatite , 1962, Nature.

[15]  Gavin Sinclair,et al.  Characterisation of spatial and temporal changes in pH gradients in microfluidic channels using optically trapped fluorescent sensors. , 2006, Lab on a chip.

[16]  L. Chow.  Next generation calcium phosphate-based biomaterials. , 2009, Dental materials journal.

[17]  W. E. Brown,et al.  The effects of magnesium and fluoride on the hydrolysis of octacalcium phosphate. , 1992, Archives of oral biology.

[18]  T. Anada,et al.  Comparative study on the resorbability and dissolution behavior of octacalcium phosphate, β-tricalcium phosphate, and hydroxyapatite under physiological conditions. , 2016, Dental materials journal.

[19]  Min-Hsien Wu,et al.  Development of high throughput optical sensor array for on-line pH monitoring in micro-scale cell culture environment , 2009, Biomedical microdevices.

[20]  J. Ko,et al.  Effect of electrostatic interaction on the adsorption of globular proteins on octacalcium phosphate crystal film. , 2002, Journal of colloid and interface science.

[21]  W. E. Brown,et al.  Infra-red spectra of hydroxyapatite, octacalcium phosphate and pyrolysed octacalcium phosphate. , 1966, Archives of oral biology.

[22]  O. Suzuki,et al.  Bone formation on synthetic precursors of hydroxyapatite. , 1991, The Tohoku journal of experimental medicine.

[23]  I. Silver.  Measurement of pH and ionic composition of pericellular sites. , 1975, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[24]  O. Suzuki,et al.  Adsorption of Bovine Serum Albumin onto Octacalcium Phosphate and its Hydrolyzates , 1995 .

[25]  S. Waldman,et al.  Effect of sodium bicarbonate on extracellular pH, matrix accumulation, and morphology of cultured articular chondrocytes. , 2004, Tissue engineering.

[26]  H. Shimauchi,et al.  Proteome analysis of rat serum proteins adsorbed onto synthetic octacalcium phosphate crystals. , 2011, Analytical biochemistry.

[27]  Dimitri Pappas,et al.  Evaluation of the Paratrend Multi-Analyte Sensor for Potential Utilization in Long-Duration Automated Cell Culture Monitoring , 2004, Biomedical microdevices.

[28]  T. Goto,et al.  Fluoride Analysis of Apatite Crystals with a Central Planar OCP Inclusion: Concerning the Role of F− Ions on Apatite/OCP/Apatite Structure Formation , 1996, Calcified Tissue International.

[29]  T. Anada,et al.  Osteoblastic differentiation of stromal ST-2 cells from octacalcium phosphate exposure via p38 signaling pathway. , 2014, Dental materials journal.

[30]  E. Itoi,et al.  Effect of partial hydrolysis of octacalcium phosphate on its osteoconductive characteristics. , 2009, Biomaterials.

[31]  Nicole J. Crane,et al.  Raman spectroscopic evidence for octacalcium phosphate and other transient mineral species deposited during intramembranous mineralization. , 2006, Bone.

[32]  Fumihito Arai,et al.  Functional gel-microbead manipulated by optical tweezers for local environment measurement in microchip , 2009 .

[33]  Guo-Li Shen,et al.  A wide pH range optical sensing system based on a sol-gel encapsulated amino-functionalized corrole. , 2006, The Analyst.

[34]  S. Nomura,et al.  Real-Time Imaging of Microscopic pH Distribution with a Two-Dimensional pH-Imaging Apparatus. , 1997, Analytical chemistry.

[35]  C. V. van Blitterswijk,et al.  Incorporation of bovine serum albumin in calcium phosphate coating on titanium. , 1999, Journal of biomedical materials research.

[36]  Helman Stern,et al.  Adaptive color space switching for tracking under varying illumination , 2005, Image Vis. Comput..

[37]  O. Suzuki,et al.  Formation of bone-like apatite enhanced by hydrolysis of octacalcium phosphate crystals deposited in collagen matrix. , 2007, Journal of biomedical materials research. Part B, Applied biomaterials.

[38]  H. Petite,et al.  The pH in the microenvironment of human mesenchymal stem cells is a critical factor for optimal osteogenesis in tissue-engineered constructs. , 2014, Tissue engineering. Part A.

[39]  O. Suzuki.  Octacalcium phosphate (OCP)-based bone substitute materials , 2013 .

[40]  M. Segal,et al.  Effect of pH, ionic charge, and osmolality on cytochrome c-mediated caspase-3 activity. , 2001, American journal of physiology. Cell physiology.

[41]  T. Anada,et al.  Immune cell response and subsequent bone formation induced by implantation of octacalcium phosphate in a rat tibia defect , 2016 .

[42]  O. Suzuki,et al.  Comparative Study on Osteoconductivity by Synthetic Octacalcium Phosphate and Sintered Hydroxyapatite in Rabbit Bone Marrow , 2006, Calcified Tissue International.

[43]  O. Suzuki.  Octacalcium phosphate: osteoconductivity and crystal chemistry. , 2010, Acta biomaterialia.

[44]  O. Suzuki,et al.  Maclura pomifera agglutinin-binding glycoconjugates on converted apatite from synthetic octacalcium phosphate implanted into subperiosteal region of mouse calvaria. , 1993, Bone and mineral.

[45]  M. Riehle,et al.  Polyelectrolyte multilayers generated in a microfluidic device with pH gradients direct adhesion and movement of cells. , 2011, Lab on a chip.