2D and 3D anticancer properties of C2-functionalised glucosamine-Pt (IV) prodrugs based on cisplatin scaffold.

A series of C2-functionalied Pt (IV) glycoconjugates based on glucosamine have been synthesised, characterised and tested as anticancer agents on a series of different 2D and 3D cancer cell lines. The carbohydrate will act as a targeted delivery system to improve the selectivity, exploiting the Warburg Effect and the GLUTs receptors that are overexpressed in most of the cancer cells. The hydroxyl at C2 of the carbohydrates does not participate in hydrogen bonding with the GLUTs receptors, making C2 an attractive position for drug conjugation as seen in literature.

Experimental measurements and CFD modelling of hydroxyapatite scaffolds in perfusion bioreactors for bone regeneration.

In the field of bone tissue engineering, particular interest is devoted to the development of 3D cultures to study bone cell proliferation under conditions similar to ones, e.g. by artificially producing mechanical stresses promoting a biological response (mechanotransduction).

Design Strategies and Biomimetic Approaches for Calcium Phosphate Scaffolds in Bone Tissue Regeneration.

Bone is a complex biologic tissue, which is extremely relevant for various physiological functions, in addition to movement, organ protection, and weight bearing. The repair of critical size bone defects is a still unmet clinical need, and over the past decades, material scientists have been expending efforts to find effective technological solutions, based on the use of scaffolds. In this context, biomimetics which is intended as the ability of a scaffold to reproduce compositional and structural features of the host tissues, is increasingly considered as a guide for this purpose.

Graphene Oxide Nanoplatforms to Enhance Cisplatin-Based Drug Delivery in Anticancer Therapy.

Chemotherapeutics such as platinum-based drugs are commonly used to treat several cancer types, but unfortunately, their use is limited by several side effects, such as high degradation of the drug before entering the cells, off-target organ toxicity and development of drug resistance. An interesting strategy to overcome such limitations is the development of nanocarriers that could enhance cellular accumulation in target cells in addition to decreasing associated drug toxicity in normal cells. Here, we aim to prepare and characterize a graphene-oxide-based 2D nanoplatform functionalised using highly branched, eight-arm polyethylene-glycol, which, owing to its high number of available functional groups, offers considerable loading capacity over its linear modalities and represents a highly potent nanodelivery platform as a versatile system in cancer therapy.

Liquid flow in scaffold derived from natural source: experimental observations and biological outcome.

This study investigates the biological effects on a 3D scaffold based on hydroxyapatite cultured with MC3T3 osteoblasts in response to flow-induced shear stress (FSS). The scaffold adopted here (B-HA) derives from the biomorphic transformation of natural wood and its peculiar channel geometry mimics the porous structure of the bone. From the point of view of fluid dynamics, B-HA can be considered a network of micro-channels, intrinsically offering the advantages of a microfluidic system.

Click Pt(IV)-Carbohydrates Pro-Drugs for Treatment of Osteosarcoma.

The selectivity cancer cells has always been a major challenge for chemotherapeutic agents and in particular for cisplatin, one of the most important anticancer drugs for the treatment of several types of tumors. One strategy to overtake this challenge is to modify the coordination sphere of the metallic center with specific vectors whose receptors are overexpressed in the tumoral cell membrane, such as monosaccharides. In this paper, we report the synthesis of four novel glyco-modified Pt(IV) pro-drugs, based on cisplatin scaffold, and their biological activity against osteosarcoma (OS), a malignant tumor affecting in particular adolescents and young adults.

Bone Regeneration in Load-Bearing Segmental Defects, Guided by Biomorphic, Hierarchically Structured Apatitic Scaffold.

The regeneration of load-bearing segmental bone defects remains a significant clinical problem in orthopedics, mainly due to the lack of scaffolds with composition and 3D porous structure effective in guiding and sustaining new bone formation and vascularization in large bone defects. In the present study, biomorphic calcium phosphate bone scaffolds (GreenBone™) featuring osteon-mimicking, hierarchically organized, 3D porous structure and lamellar nano-architecture were implanted in a critical cortical defect in sheep and compared with allograft. Two different types of scaffolds were tested: one made of ion-doped hydroxyapatite/β-tricalcium-phosphate (GB-1) and other made of undoped hydroxyapatite only (GB-2).

Biomorphic Transformations: A Leap Forward in Getting Nanostructured 3-D Bioceramics.

Obtaining 3-D inorganic devices with designed chemical composition, complex geometry, hierarchic structure and effective mechanical performance is a major scientific goal, still prevented by insurmountable technological limitations. With particular respect to the biomedical field, there is a lack in solutions ensuring the regeneration of long, load-bearing bone segments such as the ones of limbs, due to the still unmet goal of converging, in a unique device, bioactive chemical composition, multi-scale cell-conducive porosity and a hierarchically organized architecture capable of bearing and managing complex mechanical loads in a unique 3D implant. An emerging, but still very poorly explored approach in this respect, is given by biomorphic transformation processes, aimed at converting natural structures into functional 3D inorganic constructs with smart mechanical performance.

Nature-Inspired Unconventional Approaches to Develop 3D Bioceramic Scaffolds with Enhanced Regenerative Ability.

Material science is a relevant discipline in support of regenerative medicine. Indeed, tissue regeneration requires the use of scaffolds able to guide and sustain the natural cell metabolism towards tissue regrowth. This need is particularly important in musculoskeletal regeneration, such as in the case of diseased bone or osteocartilaginous regions for which calcium phosphate-based scaffolds are considered as the golden solution.

In Vitro Osteoinductivity Assay of Hydroxylapatite Scaffolds, Obtained with Biomorphic Transformation Processes, Assessed Using Human Adipose Stem Cell Cultures.

In this study, the in vitro biocompatibility and osteoinductive ability of a recently developed biomorphic hydroxylapatite ceramic scaffold (B-HA) derived from transformation of wood structures were analyzed using human adipose stem cells (hASCs). Cell viability and metabolic activity were evaluated in hASCs, parental cells and in recombinant genetically engineered hASC-eGFP cells expressing the green fluorescence protein. B-HA osteoinductivity properties, such as differentially expressed genes (DEG) involved in the skeletal development pathway, osteocalcin (OCN) protein expression and mineral matrix deposition in hASCs, were evaluated.

Heterogeneous chemistry in the 3-D state: an original approach to generate bioactive, mechanically-competent bone scaffolds.

The present work investigates heterogeneous gas-solid reactions involved in the biomorphic transformation of natural wood into large 3-D hydroxyapatite (HA) scaffolds recapitulating physico-chemical, morphological and mechanical features typical of natural bone. In particular, we found that the use of a reactive CO2/H2O gas mixture, under supercritical conditions at high pressure, permits to control heterogeneous CaO-CO2 reactions throughout the whole bulk and to direct the nucleation-growth of CaCO3 at a relatively low temperature, thus obtaining a highly reactive 3-D precursor enabling the formation of a large biomorphic HA scaffold preserving fine nanostructure by a hydrothermal process. To the best of our knowledge, the application of heterogeneous chemical reactions in the 3-D state is an original way to generate large HA scaffolds maintaining bio-relevant ionic substitutions, with specific regard to Mg2+, Sr2+ and CO32- ions, conferring a superior ability to guide cell fate.

Biomineralization of a titanium-modified hydroxyapatite semiconductor on conductive wool fibers.

Metal ions are frequently incorporated into crystalline materials to improve their electrochemical properties and to confer new physicochemical properties. Naturally-occurring phosphate apatite, which is formed geologically and in biomineralization processes, has extensive potential applications and is therefore an attractive functional material. In this study, we generate a novel building block for flexible optoelectronics using bio-inspired methods to deposit a layer of photoactive titanium-modified hydroxyapatite (TiHA) nanoparticles (NPs) on conductive polypyrrole(PPy)-coated wool yarns.

Porous NiTi shape memory alloys produced by SHS: microstructure and biocompatibility in comparison with Ti2Ni and TiNi3.

Shape memory alloys based on NiTi have found their main applications in manufacturing of new biomedical devices mainly in surgery tools, stents and orthopedics. Porous NiTi can exhibit an engineering elastic modulus comparable to that of cortical bone (12-17 GPa). This condition, combined with proper pore size, allows good osteointegration.

Biomimetic magnesium-carbonate-apatite nanocrystals endowed with strontium ions as anti-osteoporotic trigger.

The present work investigates the preparation of biomimetic nanocrystalline apatites co-substituted with Mg, CO3 and Sr to be used as starting materials for the development of nanostructured bio-devices for regeneration of osteoporotic bone. Biological-like amounts of Mg and CO3 ions were inserted in the apatite structure to mimic the composition of bone apatite, whereas the addition of increasing quantities of Sr ions, from 0 up to 12 wt.%, as anti-osteoporotic agent, was evaluated.

Biomimesis and biomorphic transformations: new concepts applied to bone regeneration.

In the last decades the activity of material scientists was more and more directed to the development of biomimetic scaffolds, able to drive and address cell activity towards proper differentiation and the repair of diseased human tissues. In case of bone, this requires the synthesis of three-dimensional constructs able to exchange chemical signals promoting osteogenesis and to progressively be resorbed during the formation and remodelling of new bone. Besides, particularly for the regeneration of extensive portions of bone, a morphological and mechanical biomimesis is also required, to allow cell colonization and formation of a proper vascularization tree.