Mn vs Co substitution into β-TCP: Structural details and bone cells response.

This work investigated the range of substitution of two biologically relevant ions, namely Mn and Co, into the structure of β-tricalcium phosphate, as well as their influence on bone cells response. To this aim, β-TCP was synthesized by solid state reaction in the presence of increasing amount of the substituent ions. The results of the X-ray diffraction analysis reveal that just limited amounts of these ions can enter into the β-TCP structure: 15 at% and 20 at% for cobalt and manganese, respectively.

Regulation of osteogenesis and angiogenesis by cobalt, manganese and strontium doped apatitic materials for functional bone tissue regeneration.

Strontium, cobalt, and manganese ions are present in the composition of bone and useful for bone metabolism, even when combined with calcium phosphate in the composition of biomaterials. Herein we explored the possibility to include these ions in the composition of apatitic materials prepared through the cementitious reaction between ion-substituted calcium phosphate dibasic dihydrate, CaHPO·2HO (DCPD) and tetracalcium phosphate, Ca(PO)O (TTCP). The results of the chemical, structural, morphological and mechanical characterization indicate that cobalt and manganese exhibit a greater delaying effect than strontium (about 15 at.

The Role of WO Nanoparticles on the Properties of Gelatin Films.

Gelatin films are very versatile materials whose properties can be tuned through functionalization with different systems. This work investigates the influence of WO nanoparticles on the swelling, barrier, mechanical, and photochromic properties of gelatin films. To this purpose, polyvinylpirrolidone (PVP)-stabilized WO nanoparticles were loaded on gelatin films at two different pH values, namely, 4 and 7.

Anti-Oxidant Multi-Functionalized Materials: Strontium-Substituted Monetite and Brushite as Delivery Systems for Curcumin.

Curcumin has numerous biological activities and pharmaceutical applications related to its ability to inhibit reactive oxygen species. Herein, strontium-substituted monetite (SrDCPA) and strontium-substituted brushite (SrDCPD) were synthesized and further functionalized with curcumin with the aim to develop materials that combine the anti-oxidant properties of the polyphenol, the beneficial role of strontium toward bone tissue, and the bioactivity of calcium phosphates. Adsorption from hydroalcoholic solution increases with time and curcumin concentration, up to about 5-6 wt%, without affecting the crystal structure, morphology, and mechanical response of the substrates.

Hydroxyapatite Decorated with Tungsten Oxide Nanoparticles: New Composite Materials against Bacterial Growth.

The availability of biomaterials able to counteract bacterial colonization is one of the main requirements of functional implants and medical devices. Herein, we functionalized hydroxyapatite (HA) with tungsten oxide (WO) nanoparticles in the aim to obtain composite materials with improved biological performance. To this purpose, we used HA, as well as HA functionalized with polyacrilic acid (HAPAA) or poly(ethylenimine) (HAPEI), as supports and polyvinylpyrrolidone (PVP) as stabilizing agent for WO nanoparticles.

Monetite vs. Brushite: Different Influences on Bone Cell Response Modulated by Strontium Functionalization.

Monetite and brushite are regarded with increasing interest for the preparation of biomaterials for applications in the musculoskeletal system. Herein, we investigated the influence of strontium substitution in the structures of these two phosphates on bone cell response. To achieve this aim, co-cultures of human primary osteoclasts and human osteoblast-like MG63 cells were tested on strontium-substituted monetite and strontium-substituted brushite, as well as on monetite and brushite, as controls.

Antiosteoporotic Nanohydroxyapatite Zoledronate Scaffold Seeded with Bone Marrow Mesenchymal Stromal Cells for Bone Regeneration: A 3D In Vitro Model.

Background: Bisphosphonates are widely employed drugs for the treatment of pathologies with high bone resorption, such as osteoporosis, and display a great affinity for calcium ions and apatitic substrates. Here, we aimed to investigate the potentiality of zoledronate functionalized hydroxyapatite nanocrystals (HAZOL) to promote bone regeneration by stimulating adhesion, viability, metabolic activity and osteogenic commitment of human bone marrow derived mesenchymal stromal cells (hMSCs).

Methods: we adopted an advanced three-dimensional (3D) in vitro fracture healing model to study porous scaffolds: hMSCs were seeded onto the scaffolds that, after three days, were cut in halves and unseeded scaffolds were placed between the two halves.

Curcumin-Functionalized Gelatin Films: Antioxidant Materials with Modulated Physico-Chemical Properties.

In this paper we used curcumin as a functionalizing agent of gelatin films with the aim to get antioxidant materials with modulated physico-chemical properties. To this aim, we prepared gelatin films at different contents of curcumin up to about 1.2 wt%.

Novel drug-loaded film forming patch based on gelatin and snail slime.

Gelatin-based films enriched with snail slime are proposed as novel biodegradable and naturally bioadhesive patches for cutaneous drug delivery. Films (thickness range 163-248 μm) were stretchable and they adhered firmly onto the wetted skin, especially those with high amount (70% V/V) of snail slime extract. Fluconazole was selected as model drug and added to films containing the highest amount of snail slime.

Strontium substituted hydroxyapatite with β-lactam integrin agonists to enhance mesenchymal cells adhesion and to promote bone regeneration.

Multi-functionalization of calcium phosphates to get delivery systems of therapeutic agents is gaining increasing relevance for the development of functional biomaterials aimed to solve problems related to disorders of the muscolo-skeletal system. In this regard, we functionalized Strontium substituted hydroxyapatite (SrHA) with some β-lactam integrin agonists to develop materials with enhanced properties in promoting cell adhesion and activation of intracellular signaling as well as in counteracting abnormal bone resorption. For this purpose, we selected two monocyclic β-lactams on the basis of their activities towards specific integrins on promoting cell adhesion and signalling.

Green synthesis of bioactive oligopeptides promoted by recyclable nanocrystalline hydroxyapatite.

The pharmaceutical industry is showing renewed interest in therapeutic peptides. Unfortunately, the chemical synthesis of peptides remains very expensive and problematic in terms of environmental sustainability. Hence, making peptides 'greener' has become a new front line for the expansion of peptide market.

Functional properties of chitosan films modified by snail mucus extract.

Snail mucus is an attractive natural substance, which is increasingly used in cosmetic creams and syrups thanks to its emollient, moisturizing, protective and reparative properties. The aim of the present study was to explore the physicochemical properties of chitosan-based films added with snail mucus extracted from Helix Aspersa Muller. To this aim, chitosan films at different content of snail mucus were fabricated by simple solvent casting technique.

Multifunctionalization Modulates Hydroxyapatite Surface Interaction with Bisphosphonate: Antiosteoporotic and Antioxidative Stress Materials.

Multifunctionalized biomaterials with enhanced bone antiresorptive properties were obtained through adsorption of a bisphosphonate, risedronate, on hydroxyapatite (HA) nanocrystals functionalized with zinc ions and polyethylenimine (PEI). Zn incorporation into the HA structure amounts to about 8 atom %, whereas the PEI content of the bifunctionalized material ZnHAPEIBP is about 5.9 wt %.

Cylindrical Layered Bone Scaffolds with Anisotropic Mechanical Properties as Potential Drug Delivery Systems.

3D cylindrical layered scaffolds with anisotropic mechanical properties were prepared according to a new and simple method, which involves gelatin foaming, deposition of foamed strips, in situ crosslinking, strip rolling and lyophilization. Different genipin concentrations were tested in order to obtain strips with different crosslinking degrees and a tunable stability in biological environment. Before lyophilization, the strips were curled in a concentric structure to generate anisotropic spiral-cylindrical scaffolds.

Strontium and Zinc Substitution in β-Tricalcium Phosphate: An X-ray Diffraction, Solid State NMR and ATR-FTIR Study.

β-tricalcium phosphate (β-TCP) is one of the most common bioceramics, widely applied in bone cements and implants. Herein we synthesized β-TCP by solid state reaction in the presence of increasing amounts of two biologically active ions, namely strontium and zinc, in order to clarify the structural modifications induced by ionic substitution. The results of X-ray diffraction analysis indicate that zinc can substitute for calcium into a β-TCP structure up to about 10 at% inducing a reduction of the cell parameters, whereas the substitution occurs up to about 80 at% in the case of strontium, which provokes a linear increase of the lattice constants, and a slight modification into a more symmetric structure.

Effect of strontium substituted ß-TCP associated to mesenchymal stem cells from bone marrow and adipose tissue on spinal fusion in healthy and ovariectomized rat.

Despite alternatives to autogenous bone graft for spinal fusion have been investigated, it has been shown that osteoconductive materials alone do not give a rate of fusion comparable with autogenous bone. This study analyzed a strontium substituted ß-tricalcium phosphate (Sr-ßTCP) associated with syngeneic, unexpanded, and undifferentiated mesenchymal stem cells from bone marrow (BMSC) or adipose tissue (ADSC) as a new tissue engineering approach for spinal fusion procedures. A posterolateral fusion was performed in 15 ovariectomized (OVX) and 15 sham-operated (SHAM) Inbred rats.

Role of Aspartic and Polyaspartic Acid on the Synthesis and Hydrolysis of Brushite.

Dicalcium phosphate dihydrate (DCPD) is one of the mineral phases indicated as possible precursors of biological apatites and it is widely employed in the preparation of calcium phosphate bone cements. Herein, we investigated the possibility to functionalize DCPD with aspartic acid (ASP) and poly-aspartic acid (PASP), as models of the acidic macromolecules of biomineralized tissues, and studied their influence on DCPD hydrolysis. To this aim, the synthesis of DCPD was performed in aqueous solution in the presence of increasing concentrations of PASP and ASP, whereas the hydrolysis reaction was carried out in physiological solution up to three days.

Antiresorptive properties of strontium substituted and alendronate functionalized hydroxyapatite nanocrystals in an ovariectomized rat spinal arthrodesis model.

Purpose: The purpose of this study was to comparatively investigate the posterolateral fusion rate in ovariectomized (OVX) rats using two new bone graft materials: strontium (Sr) substituted hydroxyapatite (HA) nanocrystals and alendronate (AL) functionalized HA nanocrystals. SrHA was synthesized in presence of different Sr concentrations (SrHA5; SrHA10) and HA-AL nanocrystals at increasing bisphosphonate (BP) content (HA-AL7; HA-AL28).

Methods: A posterolateral spinal fusion model in twenty-five Sham operated and in twenty-five OVX female rats was used and materials were bilaterally implanted between transverse processes of lumbar vertebrae.

Modulation of Alendronate release from a calcium phosphate bone cement: An in vitro osteoblast-osteoclast co-culture study.

In this study, we loaded a biomimetic calcium phosphate bone cement (CPC) with relatively high amounts of a bisphosphonate through the use of Solid Lipid Microparticles (MPs) and investigated bone cells response to the composite cements. 10, 20 and 30% w/w of Alendronate (AL) were successfully introduced into microparticles of Cutina HR and Precirol, which were prepared by means of spray-congealing technique. Addition of AL-loaded MPs to the cement composition provoked a lengthening of the setting and of the hardening processes.

Strontium-Substituted Hydroxyapatite-Gelatin Biomimetic Scaffolds Modulate Bone Cell Response.

Strontium has a beneficial role on bone remodeling and is proposed for the treatment of pathologies associated to excessive bone resorption, such as osteoporosis. Herein, the possibility to utilize a biomimetic scaffold as strontium delivery system is explored. Porous 3D gelatin scaffolds containing about 30% of strontium substituted hydroxyapatite (SrHA) or pure hydroxyapatite (HA) are prepared by freeze-drying.

()-9-Hydroxystearate-Functionalized Anticancer Ceramics Promote Loading of Silver Nanoparticles.

Functionalization of calcium phosphates for biomedical applications has been proposed as a strategy to enrich the good osteoinductive properties of these materials with specific therapeutic characteristics. Herein, we prepared and characterized hydroxyapatite nanocrystals functionalized with an anticancer agent, ()-9-hydroxystearate (HSA), and loaded with an antimicrobial agent, namely silver nanoparticles (AgNPs). Nanocrystals at two different contents of HSA, about 4 and 9 wt %, were prepared via direct synthesis in aqueous solution.

Gradient coatings of strontium hydroxyapatite/zinc β-tricalcium phosphate as a tool to modulate osteoblast/osteoclast response.

The chemistry, structure and morphology of the implant surface have a great influence on the integration of an implant material with bone tissue. In this work, we applied Combinatorial Matrix-Assisted Pulsed Laser Evaporation (C-MAPLE) to deposit gradient thin films with variable compositions of Sr-substituted hydroxyapatite (SrHA) and Zn-substituted β-tricalcium phosphate (ZnTCP) on Titanium substrates. Five samples with different SrHA/ZnTCP composition ratios were fabricated by a single step laser procedure.

A new multifunctionalized material against multi-drug resistant bacteria and abnormal osteoclast activity.

The development of new biomaterials able to favor bone formation and to inhibit bone abnormal resorption is mandatory to face the increasing number of age-related musculo-skeletal disorders. Moreover, the increasing antibiotic resistance of clinically important bacteria, which is among the main causes of implant failure, requires new antimicrobial systems. In this study, we prepared multifunctional materials consisting of hydroxyapatite-zoledronate composite crystals decorated with Ag Nanoparticles (AgNPs).

Calcium Phosphates as Delivery Systems for Bisphosphonates.

Bisphosphonates (BPs) are the most utilized drugs for the treatment of osteoporosis, and are usefully employed also for other pathologies characterized by abnormally high bone resorption, including bone metastases. Due to the great affinity of these drugs for calcium ions, calcium phosphates are ideal delivery systems for local administration of BPs to bone, which is aimed to avoid/limit the undesirable side effects of their prolonged systemic use. Direct synthesis in aqueous medium and chemisorptions from solution are the two main routes proposed to synthesize BP functionalized calcium phosphates.