Anna Tampieri

Italian National Research Council | CNR · Institute of Science and Technology for Ceramics ISTEC

This work describes the preparation, characterization and functionalization with magnetic nanoparticles of a bone tissue-mimetic scaffold composed of collagen and hydroxyapatite obtained through a biomineralization process. Bone remodeling takes place over several weeks and the possibility to follow it in vivo in a quick and reliable way is still a...

Biomineralization consists of a complex cascade of phenomena generating hybrid nano-structured materials based on organic (e.g., polymer) and inorganic (e.g., hydroxyapatite) components. Biomineralization is a biomimetic process useful to produce highly biomimetic and biocompatible materials resembling natural hard tissues such as bones and teeth....

Bioceramics are widely considered as elective materials for the regeneration of bone tissue, due to their compositional mimicry with bone inorganic components. However, they are intrinsically brittle, which limits their capability to sustain multiple biomechanical loads, especially in the case of load-bearing bone districts. In the last decades, in...

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 scaffold...

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...

Calcium phosphates (CaPs) are widely accepted biomaterials able to promote the regeneration of bone tissue. However, the regeneration of critical-sized bone defects has been considered challenging, and the development of bioceramics exhibiting enhanced bioactivity, bioresorbability and mechanical performance is highly demanded. In this respect, the...

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 region...

Microbial infections occurring during bone surgical treatment, the cause of osteomyelitis and implant failures, are still an open challenge in orthopedics. Conventional therapies are often ineffective and associated with serious side effects due to the amount of drugs administered by systemic routes. In this study, a medicated osteoinductive and bi...

Osteomyelitis (OM) is an infectious disease of the bone primarily caused by the opportunistic pathogen Staphylococcus aureus (SA). This Gram-positive bacterium has evolved a number of strategies to evade the immune response and subvert bone homeostasis, yet the underlying mechanisms remain poorly understood. OM has been modeled in vitro to challeng...

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 genet...

A 3-D porous apatite scaffold (B-HA), recently obtained through biomorphic transformation of a natural wood, is investigated on its multi-scale porous structure determining superior mechanical properties and biological behaviour. B-HA shows hierarchical pore architecture with wide aligned channels interconnected with smaller tubules, thus recapitul...

The aging of the world population is increasingly claimed as an alarming situation, since an ever-raising number of persons in advanced age but still physically active is expected to suffer from invalidating and degenerative diseases. The impairment of the endogenous healing potential provoked by the aging requires the development of more effective...

Calcium phosphate cements (CPCs) have been extensively studied in last decades as nanostructured biomaterials for the regeneration of bone defects, both for dental and orthopedic applications. However, the precise control of their handling properties (setting time, viscosity, and injectability) still represents a remarkable challenge because a comp...

Over the past decades, age-related pathologies have increased abreast the aging population worldwide. The increased age of the population indicates that new tools, such as biomaterials/scaffolds for damaged tissues, which display high efficiency, effectively and in a limited period of time, for the regeneration of the body's tissue are needed. Inde...

In bone tissue engineering, the design of 3D systems capable of recreating composition, architecture and micromechanical environment of the native extracellular matrix (ECM) is still a challenge. While perfusion bioreactors have been proposed as potential tool to apply biomechanical stimuli, its use has been limited to a low number of biomaterials....

Biomaterial science increasingly seeks more biomimetic scaffolds that functionally augment the native bone tissue. In this paper, a new concept of a structural scaffold design is presented where the physiological multi-scale architecture is fully incorporated in a single-scaffold solution. Hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioc...

The failure of the osteosarcoma conventional therapies leads to the growing need for novel therapeutic strategies. The lack of specificity for the Cancer Stem Cells (CSCs) population has been recently identified as the main limitation in the current therapies. Moreover, the traditional two-dimensional (2D) in vitro models, employed in the drug test...

The development of new materials based on abundant elements, reduced toxicity is today crucial for the next generation of energy device. Titanium-doped hydroxyapatite (TiHA) was tested for the first time as photoanode material for Dye – Sensitized Solar Cells (DSSCs). The chemical composition and energy structure of TiHA powders with increasing tit...

Bone is the third most frequent site of metastasis, with a particular incidence in breast and prostate cancer patients. For example, almost 70% of breast cancer patients develop several bone metastases in the late stage of the disease. Bone metastases are a challenge for clinicians and a burden for patients because they frequently cause pain and ca...

Osteoporosis stems from an unbalance between bone mineral resorption and deposition. Among the numerous cellular players responsible for this unbalance bone marrow (BM) monocytes/macrophages, mast cells, T and B lymphocytes, and dendritic cells play a key role in regulating osteoclasts, osteoblasts, and their progenitor cells through interactions o...

Hybrid superparamagnetic microspheres with bone-like composition, previously developed by a bio-inspired assembling/mineralization process, are evaluated for their ability to uptake and deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in therapeutically-relevant doses along with prolonged release profiles. The comparison with hybrid...

Tooth loss is a common consequence of a huge number of causes and can decrease the quality of humans’ life. Tooth is a complex organ composed of soft connective tissues and mineralized tissues of which dentin is the most voluminous component whose formation is regulated by a very complex process displaying several similarities with osteogenesis. Ca...

Scaffolds for bone regeneration have been engineered by a plethora of manufacturing technologies and biomaterials. However, the performance of these systems is often limited by lack of robustness in the process design, that hampers their scalability to clinical application. In the present study, Design of Experiment (DoE) was used as statistical to...

In the present work, hydroxyapatite (HA) nanoparticles doped with Mg2+, Sr2+, and Zn2+ ions are developed by wet neutralization method and then sintered at 1,250°C to obtain bulk consolidated materials. Physicochemical and microstructural analyses show that the presence of doping ions in the HA structure induced the formation of βTCP as secondary p...

Demineralization of dental hard tissues is a well-known health issue and the primary mechanism responsible for caries and dentinal hypersensitivity. Remineralizing toothpastes are nowadays available to improve conventional oral care formulations regarding the prevention and repair of demineralization. In this paper, we analyzed the chemical-physica...

Many studies show how biomaterial properties like stiffness, mechanical stimulation and surface topography can influence cellular functions and direct stem cell differentiation. In this work, two different natural materials, gelatin (Gel) and cellulose nanofibrils (CNFs), were combined to design suitable 3D porous biocomposites for soft-tissue engi...

Long bone defects still represent a major clinical challenge in orthopedics, with the inherent loss of function considerably impairing the quality of life of the affected patients. Thus, the purpose of this study was to assess the safety and potential of bone regeneration offered by a load‐bearing scaffold characterized by unique hierarchical archi...

Citrate and fluoride ions are two constituents of dental enamel hydroxyapatite (HA) nanocrystals. Their individual effect on HA crystallization was already studied, and it was proven that both citrate and fluoride ions regulate HA crystal growth. However, the combined effect of citrate and fluoride ions on HA nanocrystals has never been reported so...

A three dimensional magnetic patterning of two cell types was realised in vitro inside an additive manufactured magnetic scaffold, as a conceptual precursor for the vascularised tissue. The realisation of separate arrangements of vascular and osteoprogenitor cells, labelled with biocompatible magnetic nanoparticles, was established on the opposite...

Bones and hard tissues including the cartilage and teeth are of key importance for the human life, in terms of mobility, manipulation, chewing, and thus it is today one of the most demanding issues in medicine. In the last decades, a great deal of research effort has been devoted to the development of synthetic scaffolds, aiming to drive and sustai...

Materials science researchers and engineers are exploring the complex domain of biomaterials, as it requires consideration of biocompatibility and, in the frame of Regenerative Medicine, assessment on bioactivity, bio-reabsorbability and ability to be integrated and remodeled. Such a research field requires interdisciplinary approaches and robust k...

Many medical-related scientific discoveries arise from trial-error patterns where the processes involved must be refined and modified continuously before any product could be able to reach the final costumers. One of the elements affecting negatively these processes is the inaccuracy of two-dimension (2D) standard culture systems, carried over in p...

The regeneration of bone fractures, resulting from trauma, osteoporosis or tumors, is a major problem in our super-aging society. Bone regeneration is one of the main topics of concern in regenerative medicine. In recent years, stem cells have been employed in regenerative medicine with interesting results due to their self-renewal and differentiat...

A 3-D porous apatite scaffold (B-HA), recently obtained through biomorphic transformation of a natural wood, is investigated on its multi-scale porous structure determining superior biological and mechanical behaviour. B-HA shows a hierarchically organized architecture with wide aligned channels interconnected with smaller tubules, thus recapitulat...

Silks have been widely used as biomaterials due to their biocompatibility, biodegradability, and excellent mechanical properties. In the present work, native spider silk was used as organic template for controlled nucleation of hydroxyapatite (HA) nano‐coating that can act as biomimetic interface. Different bio‐inspired neutralization methods and p...

In an attempt to mimic the outstanding mechanical properties of wood and bone, a 3D heterogeneous chemistry approach has been used in a biomorphic transformation process (in which sintering is avoided) to fabricate ceramics from rattan wood, preserving its hierarchical fibrous microstructure. The resulting material (called biomorphic apatite [BA] h...

The present work describes a novel nanocrystalline, multi-doped hydroxyapatite featuring excellent eukaryotic vs. prokaryotic cell selectivity, attested by excellent osteoinductive character, evaluated with human stem cells, and anti-infective ability, tested against different pathogens. Physico-chemical analysis and TEM/STEM observations highlight...

The formation of oriented enamel-like fluoride doped hydroxyapatite (HA) nanorods on amorphous calcium phosphate (ACP) substrates in a bare form and containing citrate is compared. It is found that the presence of citrate, delays the conversion into un-oriented HA that in turn affects the overgrowth of nanorods as well as their shape and surface fe...

The effects of a large collagen-hydroxyapatite (COL-HA) substitute with or without isolated bone marrow nuclear cells (BMNC) on spine fusion were evaluated using a two-level posterolateral spinal fusion model in sheep. Six sheep each were included in both the COL-HA and autograft groups. In each animal, spine fusions were performed at two levels by...

Several biomaterials have recently been developed to address the challenge of osteochondral regeneration. Among these, chitosan holds promises both for cartilage and bone healing. The aim of this in vivo study was to evaluate the regeneration potential of a novel hybrid magnesium-doped hydroxyapatite (MgHA), collagen, chitosan-based scaffold, which...

Aim: Magnetic hyperthermia is limited by the low selective susceptibility of neoplastic cells interspersed within healthy tissues, which we aim to improve on. Materials & methods: Two superparamagnetic calcium phosphates nanocomposites, that is, iron-doped hydroxyapatite and iron oxide (Mag) nanoparticles coated with amorphous calcium phosphate (Ma...

Defective functionality of thymic epithelial cells (TECs), due to genetic mutations or injuring causes, results in altered T-cell development leading to immunodeficiency or autoimmunity. These defects cannot be corrected by hematopoietic stem cell transplantation (HSCT), while thymus transplant has not yet demonstrated to be fully curative. Here, w...

Synthetic osteoinductive materials that mimic the human osteogenic niche have emerged as ideal candidates to address this area of unmet clinical need. In this study, we evaluated the osteoinductive potential in a rabbit orthotopic model of a magnesium-doped hydroxyapatite/type I collagen (MHA/Coll) composite. The composite was fabricated to exhibit...

We report the design, fabrication and application of a novel micro-electromechanical device coupled to a confocal Raman microscope that enables in situ molecular investigations of micro-fibers under uniaxial tensile load. This device allows for the study of fibers with diameters in the range between 1 and 100 µm and lengths of several micrometers b...

Abstract Demineralization of dental hard tissue is a widespread problem and the main responsible for dental caries and dentin hypersensitivity. The most promising strategies to induce the precipitation of new mineral phase are the application of materials releasing gradually Ca2+ and PO4 3− ions or mimicking the mineral phase of the host tissue. Ho...

The regeneration of dental tissues is a still an unmet clinical need; in fact, no therapies have been completely successful in regenerating dental tissue complexes such as periodontium, which is also due to the lack of scaffolds that are able to guide and direct cell fate towards the reconstruction of different mineralized and non-mineralized denta...

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 supercrit...

The present work describes biomimetic hybrid microspheres made of collagen type I-like peptide matrix (RCP) mineralised with Fe2+/Fe3+ doping hydroxyapatite (RCPFeHA) by a bio-inspired process. Superparamagnetic RCPFeHA microspheres are obtained by emulsification of the hybrid slurries in the presence of citrate ions, to achieve a biomimetic surfac...

Biopolymers such as gelatin (Gel) and cellulose nanofibrils (CNF) have many of the essential requirements for being used as scaffolding materials in tissue regeneration; biocompatibility, surface chemistry, ability to generate homogeneous hydrogels and 3D structures with suitable pore size and interconnection, which allows cell colonization and pro...

Nanocrystalline apatites mimicking bone mineral represent a versatile platform for biomedical applications thanks to their similarity to bone apatite and the possibility to (multi)functionalize them so as to provide “à la carte” properties. One relevant domain is in particular oncology, where drug-loaded biomaterials and engineered nanosystems may...

Biomimetic scaffolds are extremely versatile in terms of chemical composition and physical properties, which can be defined to accomplish specific applications. One property that can be added is the production/release of bioactive soluble factors, either directly from the biomaterial, or from cells embedded within the biomaterial. We reasoned that...

Supporting Information Table S1. Cell growth of WT, mock‐transduced and LVhsRL‐transduced Rankl −/− MSC in 2D versus 3D culture overtime by MTT assay. Cell growth is expressed as mean fold increase values ± SEM compared to day 0.

Alternative drug delivery approaches to treat cardiovascular diseases are currently under intense investigation. In this domain, the possibility to target the heart and tailor the amount of drug dose by using a combination of magnetic nanoparticles (NPs) and electromagnetic devices is a fascinating approach. Here, an electromagnetic device based on...

The identification of alternative biocompatible magnetic NPs for advanced clinical application is becoming an important need due to raising concerns about iron accumulation in soft issues associated to the administration of superparamagnetic iron oxide nanoparticles (NPs). Here, we report on the performance of previously synthetized iron-doped hydr...

Synthetic calcium phosphates (CaPs) are the most widely accepted bioceramics for the repair and reconstruction of bone tissue defects. The recent advancements in materials science have prompted a rapid progress in the preparation of CaPs with nanometric dimensions, tailored surface characteristics, and colloidal stability opening new perspectives i...

Peptides are highly selective and efficacious for the treatment of cardiovascular and other diseases. However, it is currently not possible to administer peptides for cardiac-targeting therapy via a noninvasive procedure, thus representing scientific and technological challenges. We demonstrate that inhalation of small (<50 nm in diameter) biocompa...

The International Agency for Research on Cancer of the World Health Organization predicts that there will be 13-17 million cancer-related deaths each year worldwide by 2030. Cancer is still an unmanageable disease, even though numerous prevention, diagnosis, and therapeutic options exist. The main obstructions are late diagnosis, tumor metastasis,...