Intrafibrillar silicification of collagen scaffolds for sustained release of stem cell homing chemokine in hard tissue regeneration.

Traditional bone regeneration strategies relied on supplementation of biomaterials constructs with stem or progenitor cells or growth factors. By contrast, cell homing strategies employ chemokines to mobilize stem or progenitor cells from host bone marrow and tissue niches to injured sites. Although silica-based biomaterials exhibit osteogenic and angiogenic potentials, they lack cell homing capability. Stromal cell-derived factor-1 (SDF-1) plays a pivotal role in mobilization and homing of stem cells to injured tissues. In this work, we demonstrated that 3-dimensional collagen scaffolds infiltrated with intrafibrillar silica are biodegradable and highly biocompatible. They exhibit improved compressive stress-strain responses and toughness over nonsilicified collagen scaffolds. They are osteoconductive and up-regulate expressions of osteogenesis- and angiogenesis-related genes more significantly than nonsilicified collagen scaffolds. In addition, these scaffolds reversibly bind SDF-1α for sustained release of this chemokine, which exhibits in vitro cell homing characteristics. When implanted subcutaneously in an in vivo mouse model, SDF-1α-loaded silicified collagen scaffolds stimulate the formation of ectopic bone and blood capillaries within the scaffold and abrogate the need for cell seeding or supplementation of osteogenic and angiogenic growth factors. Intrafibrillar-silicified collagen scaffolds with sustained SDF-1α release represent a less costly and complex alternative to contemporary cell seeding approaches and provide new therapeutic options for in situ hard tissue regeneration.

Remineralization of artificial dentinal caries lesions by biomimetically modified mineral trioxide aggregate.

Fluoride-releasing restorative materials are available for remineralization of enamel and root caries. However, remineralization of dentin is more difficult than remineralization of enamel due to the paucity of apatite seed crystallites along the lesion surface for heterogeneous crystal growth. Extracellular matrix proteins play critical roles in controlling apatite nucleation/growth in collagenous tissues. This study examined the remineralization efficacy of mineral trioxide aggregate (MTA) in phosphate-containing simulated body fluid (SBF) by incorporating polyacrylic acid and sodium tripolyphosphate as biomimetic analogs of matrix proteins for remineralizing caries-like dentin. Artificial caries-like dentin lesions incubated in SBF were remineralized over a 6 week period using MTA alone or MTA containing biomimetic analogs in the absence or presence of dentin adhesive application. Lesion depths and integrated mineral loss were monitored with microcomputed tomography. The ultrastructure of baseline and remineralized lesions was examined by transmission electron microscopy. Dentin remineralization was best achieved using MTA containing biomimetic analogs regardless of whether an adhesive was applied; dentinal tubules within the remineralized dentin were occluded by apatite. It is concluded that the version of MTA employed in this study may be doped with biomimetic analogs for remineralization of unbonded and bonded artificial caries-like lesions in the presence of SBF.

Effects of calcium silicate-based materials on collagen matrix integrity of mineralized dentin.

INTRODUCTION: Calcium silicate-based materials (CSMs) are used in various endodontic procedures. The present study examined whether prolonged contact of mineralized dentin with recently commercialized versions of these materials adversely affects dentin collagen matrix integrity. METHODS: Dentin slabs prepared from extracted human third molars (7 × 3 × 0.3 mm) were divided into 3 groups on the basis of the material to which dentin was exposed (MTA Plus, Biodentine, untreated control dentin slabs) and the time period of exposure (24 hours, 1, 2, and 3 months; n = 6). Hydroxyproline assay was performed on each group's supernatant to quantify the collagen extraction amounts of each group per time period. Data were analyzed with two-factor repeated-measures analysis of variance and Holm-Sidak pair-wise comparisons (α = 0.05) to determine the effects of material and aging time on collagen extraction. Dentin slabs from the 3 months of aging group were demineralized for transmission electron microscopy examination of collagen matrix ultrastructural changes. RESULTS: Material (P = .002), aging time (P < .001), and their interactions (P = .007) significantly affected the amount of hydroxyproline (pg/mg of mineralized dentin) extracted from mineralized dentin and were significantly correlated by power regression models. Collagen degradation was identified from the surface of dentin slabs that were in direct contact with CSMs. CONCLUSIONS: Prolonged contact of mineralized dentin with CSMs has an adverse effect on the integrity of the dentin collagen matrix. However, the amount of collagen extracted was limited to the contact surface. Clinicians can continue to apply CSMs in endodontic procedures; however, caution is advised when these materials are applied to thin dentinal walls.

Effects of an experimental calcium aluminosilicate cement on the viability of murine odontoblast-like cells.

INTRODUCTION: Quick-setting calcium aluminosilicate cement with improved washout resistance is a potential substitute for calcium silicate cements in endodontics. This study examined the effect of an experimental calcium aluminosilicate cement (Quick-Set; Primus Consulting, Bradenton, FL) on the viability of odontoblast-like cells. METHODS: The biocompatibility of Quick-Set and white ProRoot MTA (WMTA; Dentsply Tulsa Dental Specialties, Tulsa, OK) cements and their eluents was evaluated using a murine dental papilla-derived odontoblast-like cell line (MDPC-23); 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to examine the effects of the 2 hydraulic cements on mitochondrial metabolic activity. Flow cytometry and confocal laser scanning microscopy were used to identify the effects of the 2 cements on cell death-induced plasma membrane permeability to fluorescent dyes and DNA stains. RESULTS: After the first week of immersion in culture medium, Quick-Set and WMTA were more cytotoxic than the Teflon-negative control (P < .05), and the cells exhibited more apoptosis/necrosis than Teflon (P < .05). After the second week of immersion, the 2 cements were as biocompatible as Teflon (P > .05), with cells exhibiting minimal apoptosis/necrosis. Eluents from the set cements at 1:1 dilution were significantly more cytotoxic that eluents at 1:10 or 1:100 dilution (P < .05). CONCLUSIONS: Quick-Set and WMTA exhibited similar cytotoxicity profiles. They possess negligible in vitro toxicologic risks after time-dependent elution of toxic components.

Quaternary ammonium silane-functionalized, methacrylate resin composition with antimicrobial activities and self-repair potential.

The design of antimicrobial polymers to address healthcare issues and minimize environmental problems is an important endeavor with both fundamental and practical implications. Quaternary ammonium silane-functionalized methacrylate (QAMS) represents an example of antimicrobial macromonomers synthesized by a sol-gel chemical route; these compounds possess flexible Si-O-Si bonds. In present work, a partially hydrolyzed QAMS co-polymerized with 2,2-[4(2-hydroxy 3-methacryloxypropoxy)-phenyl]propane is introduced. This methacrylate resin was shown to possess desirable mechanical properties with both a high degree of conversion and minimal polymerization shrinkage. The kill-on-contact microbiocidal activities of this resin were demonstrated using single-species biofilms of Streptococcus mutans (ATCC 36558), Actinomyces naeslundii (ATCC 12104) and Candida albicans (ATCC 90028). Improved mechanical properties after hydration provided the proof-of-concept that QAMS-incorporated resin exhibits self-repair potential via water-induced condensation of organic modified silicate (ormosil) phases within the polymerized resin matrix.

Subtleties of biomineralisation revealed by manipulation of the eggshell membrane.

Biocalcification of collagen matrices with calcium phosphate and biosilicification of diatom frustules with amorphous silica are two discrete processes that have intrigued biologists and materials scientists for decades. Recent advancements in the understanding of the mechanisms involved in these two biomineralisation processes have resulted in the use of biomimetic strategies to replicate these processes separately using polyanionic, polycationic or zwitterionic analogues of extracellular matrix proteins to stabilise amorphous mineral precursor phases. To date, there is a lack of a universal model that enables the subtleties of these two apparently dissimilar biomineralisation processes to be studied together. Here, we utilise the eggshell membrane as a universal model for differential biomimetic calcification and silicification. By manipulating the eggshell membrane to render it permeable to stabilised mineral precursors, it is possible to introduce nanostructured calcium phosphate or silica into eggshell membrane fibre cores or mantles. We provide a model for infiltrating the two compartmental niches of a biopolymer membrane with different intrafibre minerals to obtain materials with potentially improved structure-property relationships.

Inorganic-Organic Nanocomposite Assembly Using Collagen as Template and Sodium Tripolyphosphate as A Biomimetic Analog of Matrix Phosphoprotein.

Nanocomposites created with polycarboxylic acid alone as a stabilization agent for prenucleation clusters-derived amorphous calcium phosphate exhibit non-periodic apatite deposition. In the present study, we report the use of inorganic polyphosphate as a biomimetic analog of matrix phosphoprotein for directing polyacrylic acid-stabilized amorphous nanoprecursor phases to assemble into periodic apatite-collagen nanocomposites. The sorption and desorption characteristics of sodium tripolyphosphate to type I collagen was examined. Periodic nanocomposite assembly with collagen as a template was demonstrated with TEM and SEM using a Portland cement-based resin composite and a phosphate-containing simulated body fluid. Apatite was detected within the collagen at 24 hours and became more distinct at 48 hours, with prenucleation clusters attaching to the collagen fibril surface during the initial infiltration stage. Apatite-collagen nanocomposites at 72 hours were heavily mineralized with periodically-arranged intrafibrillar apatite platelets. Defect-containing nanocomposites caused by desorption of TPP from collagen fibrils were observed in regions lacking the inorganic phase.