Development of bifunctional oriented bioactive glass/poly(lactic acid) composite scaffolds to control osteoblast alignment and proliferation

During the bone regeneration process, the anisotropic microstructure of bone tissue (bone quality) recovers much later than bone mass (bone quantity), resulting in severe mechanical dysfunction in the bone. Hence, restoration of bone microstructure in parallel with bone mass is necessary for ideal bone tissue regeneration; for this, development of advanced bifunctional biomaterials, which control both the quality and quantity in regenerated bone, is required. We developed novel oriented bioactive glass/poly(lactic acid) composite scaffolds by introducing an effective methodology for controlling cell alignment and proliferation, which play important roles for achieving bone anisotropy and bone mass, respectively. Our strategy is to manipulate the cell alignment and proliferation by the morphological control of the scaffolds in combination with controlled ion release from bioactive glasses. We quantitatively controlled the morphology of fibermats containing bioactive glasses by electrospinning, which successfully induced cell alignment along the fibermats. Also, the substitution of CaO in Bioglass®(45S5) with MgO and SrO improved osteoblast proliferation, indicating that dissolved Mg 2+ and Sr 2+ ions promoted cell adhesion and proliferation. Our results indicate that the fibermats developed in this work are candidates for the scaffolds to bone tissue regeneration that enable recovery of both bone quality and bone quantity. © 2019 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1031–1041, 2019.Lee S., Matsugaki A., Kasuga T., et al. Development of bifunctional oriented bioactive glass/poly(lactic acid) composite scaffolds to control osteoblast alignment and proliferation. Journal of Biomedical Materials Research - Part A, 107, 5, 1031. https://doi.org/10.1002/jbm.a.36619

Oriented siloxane-containing vaterite/poly(lactic acid) composite scaffolds for controlling osteoblast alignment and proliferation

Bone tissue has an anisotropic structure, which is strongly associated with the collagen fibril orientation and the direction of the c-axis of the bone apatite crystal. The bone regeneration process contains two main phases: bone mineral density (BMD; bone quantity) restoration and reconstruction of the bone apatite c-axis orientation (bone quality), which is the dominant factor for the mechanical properties of bone. Hence, restoration of the bone quality and quantity is required for bone tissue regeneration. In this work, novel, oriented siloxane-containing vaterite/poly(lactic acid) composite scaffolds were developed by controlling the cell alignment and proliferation, which play an important role in regenerating the bone quality and quantity, respectively. Our strategy controlled the cell alignment and proliferation using a morphological design of the scaffolds and the ions released from the siloxane-containing vaterite. The scaffolds were designed to control of the cell alignment, which successfully induced cell orientation along the fibermats. In addition, the released ions from the siloxane-containing vaterite improved osteoblast proliferation, indicating that the released Mg 2+ and silicate ions stimulated cell adhesion and proliferation. These results indicated that the fibermats developed in this work could be used for bone tissue regeneration scaffolds that enable the recovery of bone quality and quantity.Lee S., Kiyokane Y., Kasuga T., et al. Oriented siloxane-containing vaterite/poly(lactic acid) composite scaffolds for controlling osteoblast alignment and proliferation. Journal of Asian Ceramic Societies, 7, 2, 228. https://doi.org/10.1080/21870764.2019.1599528

Development of orthophosphosilicate glass/poly(lactic acid) composite anisotropic scaffolds for simultaneous reconstruction of bone quality and quantity

Reconstruction of organ-specific architecture is necessary to recover the original organ function. The anisotropic structure of bone tissue is strongly related to the collagen fibril alignment and bone apatite crystal direction. Bone regeneration indicates following two main process; first, restoration of bone mineral density (BMD; bone quantity), and second, restoring bone apatite c-axis orientation (bone quality). In addition to BMD, bone quality is the most important factor among bone mechanical properties. Recovery of the original bone function requires development of novel scaffolds with simultaneous reconstruction of bone quality and quantity. Herein, novel orthophosphosilicate glass (PSG)/poly(lactic acid) composite anisotropic scaffolds were developed to control cell alignment and enhance bone formation, which are important for the simultaneous reconstruction of bone quality and quantity. The strategy to control cell alignment and bone formation involved designing anisotropic scaffolds in combination with the release of therapeutic ions by PSGs. The morphology of fibrous scaffolds containing PSGs was quantitatively designed using electrospinning. This successfully modulated cell alignment and subsequent bone apatite c-axis orientation along the fiber-oriented direction. The released silicate and Mg2+ ions from PSGs in scaffolds improved cell adhesion, proliferation, and calcification. To best of our knowledge, this is the first report demonstrating that the anisotropic scaffolds containing bioactive glasses regenerate bone tissues with simultaneous reconstruction of bone quality and quantity via stimulating osteoblasts by inorganic ions and designing morphology of scaffolds.Lee S., Nagata F., Kato K., et al. Development of orthophosphosilicate glass/poly(lactic acid) composite anisotropic scaffolds for simultaneous reconstruction of bone quality and quantity. Journal of Biomedical Materials Research - Part A, 109, 5, 788. https://doi.org/10.1002/jbm.a.37067

Structures and dissolution behaviors of quaternary CaO-SrO-P₂O₅-TiO₂ glasses

Calcium phosphate glasses have a high potential for use as biomaterials because their composition is similar to that of the mineral phase of bone. Phosphate glasses can dissolve completely in aqueous solution and can contain various elements owing to their acidity. Thus, the glass can be a candidate for therapeutic ion carriers. Recently, we focused on the effect of strontium ions for bone formation, which exhibited dual effects of stimulating bone formation and inhibiting bone resorption. However, large amounts of strontium ions may induce a cytotoxic effect, and there is a need to control their releasing amount. This work reports fundamental data for designing quaternary CaO-SrO-P₂O₅-TiO₂ glasses with pyro- and meta-phosphate compositions to control strontium ion-releasing behavior. The glasses were prepared by substituting CaO by SrO using the melt-quenching method. The SrO/CaO mixed composition exhibited a mixed cation effect on the glassification degree and ion-releasing behavior, which showed non-linear properties with mixed cation compositions of the glasses. Sr²⁺ ions have smaller field strength than Ca²⁺ ions, and the glass network structure may be weakened by the substitution of CaO by SrO. However, glassification degree and chemical durability of pyro- and meta-phosphate glasses increased with substituted all CaO by SrO. This is because titanium groups in the glasses are closely related to their glass network structure by SrO substitution. The P-O-Ti bonds in pyrophosphate glass series and TiO₄ tetrahedra in metaphosphate glass series increased with substitution by SrO. The titanium groups in the glasses were crosslink and/or coordinate phosphate groups to improve glassification degree and chemical durability. Sr²⁺ ion releasing amount of pyrophosphate glasses with >83% SrO substitution was larger than 0.1 mM at day seven, an amount that reported enhanced bone formation by stimulation of osteogenic markers.Lee S., Nagata F., Kato K., et al. Structures and dissolution behaviors of quaternary CaO-SrO-P₂O₅-TiO₂ glasses. Materials, 14, 7, 1736. https://doi.org/10.3390/ma14071736

Structural effects of phosphate groups on apatite formation in a copolymer modified with Ca2+ in a simulated body fluid

Organic–inorganic composites are novel bone substitutes that can ameliorate the mismatch of Young\u27s moduli between natural bone and implanted ceramics. Phosphate groups contribute to the formation of apatite in a simulated body fluid (SBF) and the adhesion of osteoblast-like cells. Therefore, modification of a polymer with these functional groups is expected to enhance the ability of the organic–inorganic composite to bond with bone. Two phosphate groups have been used, phosphonic acid (–C–PO3H2) and phosphoric acid (–O–PO3H2). However, the effects of structural differences between these phosphate groups have not been clarified. In this study, the apatite formation of copolymers modified with Ca2+ and either –C–PO3H2 or –O–PO3H2 was examined. The mechanism of apatite formation is discussed based on analytical and computational approaches. The copolymers containing –O–PO3H2, but not those containing –C–PO3H2, formed apatite in the SBF, although both released similar amounts of Ca2+ into the SBF. Adsorption of HPO42− from –O–PO3H2 in the SBF following Ca2+ adsorption was confirmed by zeta-potential measurement and X-ray photoelectron spectroscopy. The measurement of the complex formation constant revealed that the –O–PO32−⋯Ca2+ complex was thermodynamically unstable enough to convert into CaHPO4, which was not the case with –C–PO32−⋯Ca2+. The formation of CaHPO4-based clusters was found to be a key factor for apatite nucleation. In conclusion, this study revealed that modification with –O–PO3H2 was more effective for enhancing apatite formation compared with –C–PO3H2