Barbara Palazzo

Surface enamel remineralization: biomimetic apatite nanocrystals and fluoride ions different effects

A new method for altered enamel surface remineralization has been proposed. To this aim carbonate-hydroxyapatite nanocrystals which mimic for composition, structure, nanodimensions, and morphology dentine apatite crystals and resemble closely natural apatite chemical-physical properties have been used The results underline the differences induced by the use of fluoride ions and hydroxyapatite nanocrystals in contrasting the mechanical abrasions and acid attacks to which tooth enamel is exposed. Fluoride ions generate a surface modification of the natural enamel apatite crystals increasing their crystallinity degree and relative mechanical and acid resistance. On the other hand, the remineralization produced by carbonate-hydroxyapatite consists in a deposition of a new apatitic mineral into the eroded enamel surface scratches. A new biomimetic mineral coating, which progressively fills and shadows surface scratches, covers and safeguards the enamel structure by contrasting the acid and bacteria attacks.

Adsorption and conformational change of myoglobin on biomimetic hydroxyapatite nanocrystals functionalized with alendronate.

The chemical conjugation of bisphosphonates (BPs), specifically alendronate, to hydroxyapatite could be an effective means to impart to it fine-tuned bioactivity. Horse heart myoglobin (Mb), a well-characterized protein, has been adsorbed onto biomimetic hydroxyapatite nanocrystals (nHA) and onto the nHA/alendronate conjugate powdered samples. The obtained materials have potential use in bone implantation and as prospective drug-delivery devices. The kinetic absorption of Mb onto nHA is dramatically affected by its functionalization with alendronate. The covering of the nHA surface by alendronate inhibits the adsorption of myoglobin. The adsorption mechanisms of the protein were studied by spectroscopic techniques (UV-vis and surface-enhanced Raman spectroscopy). The results indicate that the protein changes conformation upon adsorption on the inorganic substrate. In particular, the interaction with nHA alters the coordination state of the iron in the heme through the formation of a hexacoordinated low-spin Mb heme, possibly involving the distal histidine. Instead, the covering of the nHA surface by alendronate does not adsorb the protein but preserves the coordination state of the heme moiety. This study could be of significance either in the field of biomaterials science, in particular, to fine tune a bone-specific drug delivery device and to test nHA as a new support for heterogeneous catalysis, improving the understating of enzyme immobilization.

Smart delivery of antitumoral platinum complexes from biomimetic hydroxyapatite nanocrystals

This study widens the role of biomimetic hydroxyapatite (HA) nanocrystals as bone substitutes and describes how they can be used as bone-specific drug delivery devices for in situ treatment of bone tumors upon local implantation. The adsorption and release kinetics of bis-{ethylenediamineplatinum(II)}-2-amino-1-hydroxyethane-1,1-diyl-bisphosphonate and bis-{ethylenediamineplatinum(II)}medronate on two kinds of HA nanocrystals having different morphologies, crystallinity degrees and surface areas have been investigated. The different chemical structures of the two Pt complexes appreciably affect not only the affinity towards the two kinds of HA, but also their release. The Pt complex loading is slightly greater for the HA characterized by lower crystallinity and higher surface area, with respect to the more crystalline one. The cytotoxicity of Pt complexes released from the HA were tested against human cervix carcinoma cells and, interestingly, were found to be more cytotoxic than the unmodified complexes. The released Pt species are therefore the active dichloridoethylenediamineplatinum(II) or related solvato species formed by Pt-bisphosphonate bond breaking.

The role of biomimetism in developing nanostructured inorganic matrices for drug delivery

Background: Biomimetism of synthetic biomaterials can be carried out at different levels, such as composition, structure, morphology, bulk and surface chemical–physical properties. Biomaterials can be turned into biomimetic imprinting of all these characteristics in order not only to optimise their interaction with biological tissues, but also to mimic biogenic materials in their functionalities. Objective: This review outlines the biomimetic chemical–physical properties of inorganic matrices in controlling drug release. Methods: This review is restricted to phosphates and silica among inorganic biomaterials proposed as drug delivery vehicles. Conclusion: By mimicking nature, we can design and synthesise inorganic smart materials that are reactive towards biological tissues and can release bioactive molecules by a kinetic that is controlled not only by the matrix tailored chemical–physical properties, but also by the response to stimuli induced by physiological or pathological processes.

Synthetic Biomimetic Carbonate-Hydroxyapatite Nanocrystals for Enamel Remineralization

New biomimetic carbonate-hydroxyapatite nanocrystals (CHA) have been designed and synthesized in order to obtain a remineralization of the altered enamel surfaces. Synthesized CHA mimic for composition, structure, nano dimension and morphology bone apatite crystals and their chemical-physical properties resemble closely those exhibited by enamel natural apatite. CHA can chemically bound themselves on the surface of natural enamel apatite thanks to their tailored biomimetic characteristics. The remineralization effect induced by CHA represents a real new deposition of carbonate-hydroxyapatite into the eroded enamel surface scratches forming a persistent biomimetic mineral coating, which covers and safeguards the enamel structure. The experimental results point out the possibility to use materials alternative to fluoride compounds which is commonly utilized to contrast the mechanical abrasions and acid attacks. The apatitic synthetic coating is less crystalline than enamel natural apatite, but consists of a new biomimetic apatitic mineral deposition which progressively fills the surface scratches. Therefore the application of biomimetic CHA may be considered an innovative approach to contrast the acid and bacteria attacks.

Nanocrystalline carbonate-apatites: role of Ca/P ratio on the upload and release of anticancer platinum bisphosphonates

In the present study two nanocrystalline apatites have been investigated as bone-specific drug delivery devices to be used for treatment of bone tumors either by local implantation or by injection. In order to assess how the Ca/P ratio can influence the adsorption and release of anticancer platinum-bisphosphonate complexes, two kinds of apatite nanocrystals having different Ca/P ratios but similar morphologies, degree of crystallinity, and surface areas have been synthesized and characterized. The two platinum-bisphosphonate complexes considered were the bis-{ethylenediamineplatinum(ii)}-2-amino-1-hydroxyethane-1,1-diyl-bisphosphonate and the bis-{ethylenediamineplatinum(ii)}medronate. The Ca/P ratio plays an important role in the adsorption as well as in the release of the two drugs. In fact, the apatite with a higher Ca/P ratio showed greater affinity for both platinum complexes. Also the chemical structure of the two Pt complexes appreciably affects their affinity towards as well as their release from the two kinds of apatites. In particular, the platinum complex whose bisphosphonate contains a free aminic group showed greater upload and smaller release. The cytotoxicity of the Pt complexes released from the apatite was tested against human cervical, colon, and lung cancer cells as well as against osteosarcoma cells. In agreement with previous work, the Pt complexes released were found to be more cytotoxic than the unmodified complexes.

Agarose Gel as Biomaterial or Scaffold for Implantation Surgery: Characterization, Histological and Histomorphometric Study on Soft Tissue Response

Maxillofacial, orthopedic, oral, and plastic surgery require materials for tissue augmentation, guided regeneration, and tissue engineering approaches. In this study, the aim was to develop and characterize a new extrudable hydrogel, based on agarose gel (AG; 1.5% wt) and to evaluate the local effects after subcutaneous implantation in comparison with collagen and hyaluronic acid. AG chemical–physical properties were ascertained through Fourier transform infrared (FT-IR) spectroscopy and rheological analysis. In vivo subcutaneous implants were performed, and histological and histomorphometric evaluations were done at 1, 4, 12, and 16 weeks. FT-IR confirmed that spectroscopic properties were the same for the baseline agarose and rheological characterization established that AG is a weak hydrogel. Subcutaneous AG implants induced new vessels and fibrous tissue formation rich in neutrophils; the capsule thickness around AG increased until the 12th week but remained thinner than those around hyaluronic acid and collagen. At 16 weeks, the thickness of the capsule significantly decreased around all materials. This study confirmed that 1.5% wt AG possesses some of the most important features of the ideal biocompatible material: safety, effectiveness, costless, and easily obtained with specific chemical and geometrical characters; the AG can represent a finely controllable and biodegradable polymeric system for cells and drug delivery applications.

The Remineralizing Effect of Carbonate-Hydroxyapatite Nanocrystals on Dentine

The use of specific remineralizing agents in toothpastes may help to prevent caries and treat dentinal sensitivity. In this study, applied nanotechnologies were used to develop a filler for toothpastes with remineralizing properties. Carbonate hydroxyapatite nanocrystals, with size, morphology, chemical composition and crystallinity comparable with that of dentine, were synthesized in mild condition. The remineralizing effect was studied with a scanning electron microscopy putting materials onto the slices of dentine previously demineralized with ortophosphoric acid. The application of the materials showed the progressive closure of the tubular openings of the dentine with plugs within 10 minutes and a regeneration of a surface mineral layer within 6 hours. This rates of remineralization seems to be compatible with the development of toothpastes with remineralizing effect.

Helical domain collagen substrates mineralization in simulated body fluid

Helical domain collagen substrates had been mineralized using simulated body fluid. They had an increasing level of structural organization; being in the form of gel, film, and uniaxial deformed film. The experiments were carried out for different periods of time and the obtained composite materials were characterized in their mineral content. Apatite precipitation was detected. The results show that the helical domain collagen substrates partially inhibit the in vitro apatite precipitation processes, but the amount and the crystallinity of deposited mineral can be controlled by the different assemblies of the helical domain collagen fibers.

Bisphosphonate complexation and calcium doping in silica xerogels as a combined strategy for local and controlled release of active platinum antitumor compounds

The production of bone substitute biomimetic materials which could also act as antitumoral drug release agents is of enormous interest. We report in this paper the synthesis and characterization of a novel platinum dinuclear complex containing a geminal bisphosphonate and its embodiment into xerogels prepared by the sol-gel method. Our goal was to obtain a hybrid inorganic matrix that could release a platinum species active against bone tumors or metastases, upon local implant. Two silica xerogels were considered: one was composed of pure silica, while the other contained also some calcium as potential release-modulating agent thanks to its high affinity for bisphophonates. The platinum-complex loading capacity of the inorganic matrices, the release kinetics in buffer simulating physiological conditions, and the stability upon storage were investigated as a function of Pt-complex concentration and calcium addition. We found that the presence of calcium in the composites deeply influences not only the stability of the formulations but also the nature of the platinum complex liberated in solution.