Cristina Canal

Calcium phosphate cements as drug delivery materials

Calcium phosphate cements are used as synthetic bone grafts, with several advantages, such as their osteoconductivity and injectability. Moreover, their low-temperature setting reaction and intrinsic porosity allow for the incorporation of drugs and active principles in the material. It is the aim of the present work to: a) provide an overview of the different approaches taken in the application of calcium phosphate cements for drug delivery in the skeletal system, and b) identify the most significant achievements. The drugs or active principles associated to calcium phosphate cements are classified in three groups, i) low molecular weight drugs; ii) high molecular weight biomolecules; and iii) ions.

Wettability, ageing and recovery process of plasma-treated polyamide 6

The wetting properties of polyamide 6 rods treated with radiofrequency (RF) low-temperature plasma (LTP) using three different non-polymerizing gases (air, nitrogen and water vapour) were determined using the Wilhelmy contact-angle technique. Information on the acidic or basic nature of the ionizable groups generated on the rod surface was obtained using contact-angle titration. The wettability obtained depends on the plasma gas used, and it tends to decrease with time elapsed after the treatment when the samples are kept in an air environment. However, the wettability can be recovered by immersion of the aged samples in water. The degree of recovery depends on the plasma gas used and the highest recovery was obtained with water vapour plasma treated samples. Both ageing and recovery behaviour can be attributed to the reorganisation of hydrophilic groups which tend to reversibly migrate or orient towards the bulk phase depending on the storage conditions, although other factors can also have influence.

Fibre-reinforced calcium phosphate cements: a review

Calcium phosphate cements (CPC) consist of one or more calcium orthophosphate powders, which upon mixing with water or an aqueous solution, form a paste that is able to set and harden after being implanted within the body. Different issues remain still to be improved in CPC, such as their mechanical properties to more closely mimic those of natural bone, or their macroporosity to favour osteointegration of the artificial grafts. To this end, blends of CPC with polymer and ceramic fibres in different forms have been investigated. The present work aims at providing an overview of the different approaches taken and identifying the most significant achievements in the field of fibre-reinforced calcium phosphate cements for clinical applications, with special focus on their mechanical properties.

Drug delivery from injectable calcium phosphate foams by tailoring the macroporosity-drug interaction

In this work, novel injectable calcium phosphate foams (CPFs) were combined with an antibiotic (doxycycline) to design an innovative dosage form for bone regeneration. The material structure, its drug release profile and antibiotic activity were investigated, while its clinical applicability was assessed through cohesion and injectability tests. Doxycycline had a clear effect on both the micro and macro structure of the CPFs, owing to its role as a nucleating agent of hydroxyapatite and to a drying effect on the paste. Doxycycline-loaded CPFs presented interconnected macroporosity, which increased drug availability compared with calcium phosphate cements, and was a critical parameter controlling the release kinetics which followed a non-Fickian diffusion model. Up to 55% (1mg) of the drug was released progressively in 5days, the percentage released being proportional to the macroporosity of the CPFs. All doxycycline-containing foams had immediate cohesion and were injectable. Moreover, antibacterial activity was observed against Staphylococcus aureus and Escherichia coli. Thus, in addition to enhancing osteoconduction and material resorption, macroporosity enables tuning of the local delivery of drugs from injectable calcium phosphates.

Relevance of microstructure for the early antibiotic release of fresh and pre-set calcium phosphate cements

Calcium phosphate cements (CPCs) have great potential as carriers for controlled release and vectoring of drugs in the skeletal system. However, a lot of work still has to be done in order to obtain reproducible and predictable release kinetics. A particular aspect that adds complexity to these materials is that they cannot be considered as stable matrices, since their microstructure evolves during the setting reaction. The aims of the present work were to analyze the effect of the microstructural evolution of the CPC during the setting reaction on the release kinetics of the antibiotic doxycycline hyclate and to assess the effect of the antibiotic on the microstructural development of the CPC. The incorporation of the drug in the CPC modified the textural and microstructural properties of the cements by acting as a nucleating agent for the heterogeneous precipitation of hydroxyapatite crystals, but did not affect its antibacterial activity. In vitro release experiments were carried out on readily prepared cements (fresh CPCs), and compared to those of pre-set CPCs. No burst release was found in any formulation. A marked difference in release kinetics was found at the initial stages; the evolving microstructure of fresh CPCs led to a two-step release. Initially, when the carrier was merely a suspension of α-TCP particles in water, a faster release was recorded, which rapidly evolved to a zero-order release. In contrast, pre-set CPCs released doxycycline following non-Fickian diffusion. The final release percentage was related to the total porosity and entrance pore size of each biomaterial.

Regulation of surface hydrophilicity of plasma treated wool fabrics

In this study, a set of experiments was carried out with the aim of gradually conferring hydrophobic properties to a low temperature plasma-treated wool fiber surface by post-reaction with hydrocarbon chains of different chain length. This study revealed the close relationship between the hydrophobic/hydrophilic properties of the wool surface with its shrinkage properties.

Development and Characterization of Biphasic Hydroxyapatite/β‐TCP Cements

Biphasic calcium phosphate bioceramics composed of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) have relevant properties as synthetic bone grafts, such as tunable resorption, bioactivity, and intrinsic osteoinduction. However, they have some limitations associated to their condition of high-temperature ceramics. In this work self-setting Biphasic Calcium Phosphate Cements (BCPCs) with different HA/β-TCP ratios were obtained from self-setting α-TCP/β-TCP pastes. The strategy used allowed synthesizing BCPCs with modulated composition, compressive strength, and specific surface area. Due to its higher solubility, α-TCP was fully hydrolyzed to a calcium-deficient HA (CDHA), whereas β-TCP remained unreacted and completely embedded in the CDHA matrix. Increasing amounts of the non-reacting β-TCP phase resulted in a linear decrease of the compressive strength, in association to the decreasing amount of precipitated HA crystals, which are responsible for the mechanical consolidation of apatitic cements. Ca2+ release and degradation in acidic medium was similar in all the BCPCs within the timeframe studied, although differences might be expected in longer term studies once β-TCP, the more soluble phase was exposed to the surrounding media.

Antifouling coatings for dental implants: Polyethylene glycol-like coatings on titanium by plasma polymerization

Titanium dental implants are commonly used for the replacement of lost teeth, but they present a considerable number of failures due to the infection on surrounding tissues. The aim of this paper is the development of a polyethylene glycol-like (PEG-like) coating on the titanium surface by plasma polymerization to obtain a novel improved surface with suitable low bacterial adhesion and adequate cell response. Surface analysis data of these coatings are presented, in particular, water contact angle, surface roughness, and film chemistry, demonstrating the presence of a PEG-like coating. Streptococcus sanguinis and Lactobacillus salivarius bacterial adhesion assays showed a decreased adhesion on the plasma polymerized samples, while cell adhesion of fibroblasts and osteoblasts on the treated surfaces was similar to control surfaces. Thus, the PEG-like antifouling coating obtained by plasma polymerization on Ti confers this biomaterials highly suitable properties for dental applications, as they reduce the possibility of infection while allowing the tissue integration around the implant.

Multiple characterization study on porosity and pore structure of calcium phosphate cements

UNLABELLED Characterization of the intricate pore structure of calcium phosphate cements is a key step to successfully link the structural properties of these synthetic bone grafts with their most relevant properties, such as in vitro or in vivo behaviour, drug loading and release properties, or degradation over time. This is a challenging task due to the wide range of pore sizes in calcium phosphate cements, compared to most other ceramic biomaterials. This work provides a critical assessment of three different techniques based on different physical phenomena, namely mercury intrusion porosimetry (MIP), Nitrogen sorption, and thermoporometry (TPM) for the detailed characterization of four calcium phosphate cements with different textural properties in terms of total porosity, pore size distribution (PSD), and pore entrance size distribution (PESD). MIP covers a much wider size range than TPM and Nitrogen sorption, offering more comprehensive information at the micrometer level. TPM, and especially Nitrogen sorption, are non-destructive techniques and, although they cover a limited size range, provide complementary information regarding pore structure associated with crystal shape at the nanoscale, recording both PSD and PESD in a single experiment. MIP tended to register smaller sizes, especially at low L/P ratios, due to the network effect, which has a strong influence on the outcome of this technique. STATEMENT OF SIGNIFICANCE The detailed characterisation of the porosity of calcium phosphate cements is of paramount importance, since it is a key parameter influencing some of the most relevant features, like mechanical properties, degradation rate or drug loading and release kinetics. However, this is a challenging task because, once hardened, calcium phosphate cements present an intricate morphology, consisting of a network of precipitated crystals, which generate a high intrinsic micro/nano porosity, with pore sizes covering six orders of magnitude. This work provides for the first time a critical assessment of the advantages and limitations of three different techniques, namely mercury intrusion porosimetry, Nitrogen sorption and Thermoporometry, for the characterisation of the porosity of four calcium phosphate cements with different textural properties.

Biofunctional polyethylene glycol coatings on titanium: an in vitro-based comparison of functionalization methods

Three methods for the production of Polyethylene glycol (PEG) coatings on titanium are compared, i.e. plasma polymerization, electrodeposition and silanization. The compared deposition methods presented similar wettability (hydrophilic coatings), chemical composition assessed by XPS and thickness around 1nm. The coatings lowered albumin adsorption and presented a decreased fibroblast, Streptococcus sanguinis and Lactobacillus salivarius adhesion. Immobilization of a cell adhesion peptide (RGD) presented a higher fibroblast adhesion and no alteration of the bacterial adhesion, giving three methods for the biofunctionalization of titanium for dental implants. The feasibility of each methodology is compared in terms of the process parameters in order to provide a guide for the election of the methodology.