A modified Delphi consensus for rehabilitations anchored to zygomatic implants.

BACKGROUND: Studies on different surgical approaches have been published with excellent success rates for zygomatic implants. The same publications offer different results regarding the complications associated with the use of such implants. A consensus protocol on zygomatic implant interventions has yet to be documented. PURPOSE: To seek to establish a consensus at each step of treatment consisting of oral rehabilitation using zygomatic implant-anchored restorations, and to share the outcome of the process to serve as a basis for practitioners and researchers. MATERIALS AND METHODS: A wide variety of protocols were identified based on the results of a literature review conducted previously. All participants received the results of the systematic literature search. A modified Delphi process was used to establish a consensus protocol. Six sections were defined: Diagnosis and indications, Planning, Medication, Surgery, Prosthesis, and Follow-up. The first round of 17 open-ended questions was shared with 63 participants, all of whom were experts in zygomatic implant rehabilitation and part of the ZAGA Centers network. A total of 77 follow-up questions were then generated after analysis of the responses to the first 17 questions. RESULTS: Of the 63 experts enrolled, 48 responded to both rounds of questions. Consensus was determined based on the percentage of agreement: < 70% was considered "no consensus" and ≥ 70% was considered "consensus". A high level of consensus was reached. The sections with the lowest percentage of agreement were Medication and Surgery, where a consensus was reached for 67% of the questions. Of the questions included in the Follow-up section in both rounds, a consensus was reached for 80%. Overall, agreement was obtained on 71% of the topics. CONCLUSIONS: Use of the modified Delphi process led to the creation of the first consensus protocol for oral restorations anchored to zygomatic implants.

Success Rates of Zygomatic Implants for the Rehabilitation of Severely Atrophic Maxilla: A Systematic Review.

Zygomatic implants are a treatment solution for patients with severe maxillary atrophy. This treatment option allows delivering immediate fixed teeth within 24 h. Numerous peer-reviewed publications have reported different success rates, resulting in a disagreement on the topic. Therefore, the overall efficacy and predictability of this rehabilitation is still a matter of discussion. With this study, we aimed to identify the published literature on the use of zygomatic implants for the reconstruction of the severely atrophic maxilla and report the cumulative success rate (CSR) as a function of follow-up time. A systematic review of the literature on zygomatic implant for the treatment of severe maxillary atrophy was performed and 196 publications were included in the study. The cumulative success rate of zygomatic implants for the treatment of severe maxillary atrophy was 98.5% at less than 1 year, 97.5% between 1 and 3 years, 96.8% between 3 and 5 years and 96.1% after more than 5 years. The most commonly reported complications were soft tissue dehiscence, rhinosinusitis and prosthetic failures. The treatment of severe lack of bone in the upper maxilla with zygomatic implants is a safe procedure, reaching a cumulative success rate of 96.1% after more than 5 years.

Computed tomography and histological evaluation of xenogenic and biomimetic bone grafts in three-wall alveolar defects in minipigs.

OBJECTIVES: This study aimed to compare the performance of a xenograft (XG) and a biomimetic synthetic graft (SG) in three-wall alveolar defects in minipigs by means of 3D computerised tomography and histology. MATERIALS AND METHODS: Eight minipigs were used. A total of eight defects were created in the jaw of each animal, three of which were grafted with XGs, three with SGs, and two were left empty as a negative control. The allocation of the different grafts was randomised. Four animals were euthanised at 6 weeks and four at 12 weeks. The grafted volume was then measured by spiral computed tomography to assess volume preservation. Additionally, a histological analysis was performed in undecalcified samples by backscattered scanning electron microscopy and optical microscopy after Masson's trichrome staining. RESULTS: A linear mixed-effects model was applied considering four fixed factors (bone graft type, regeneration time, anatomic position, and maxilla/mandible) and one random factor (animal). The SG exhibited significantly larger grafted volume (19%) than the XG. The anterior sites preserved better the grafted volume than the posterior ones. Finally, regeneration time had a positive effect on the grafted volume. Histological observations revealed excellent osseointegration and osteoconductive properties for both biomaterials. Some concavities found in the spheroidal morphologies of SGs were associated with osteoclastic resorption. CONCLUSIONS: Both biomaterials met the requirements for bone grafting, i.e. biocompatibility, osseointegration, and osteoconduction. Granule morphology was identified as an important factor to ensure a good volume preservation. CLINICAL RELEVANCE: Whereas both biomaterials showed excellent osteoconduction, SGs resulted in better volume preservation.

Vertical Bone Regeneration with Synthetic Biomimetic Calcium Phosphate onto the Calvaria of Rats.

IMPACT STATEMENT: This work reports a new bone substitute made of precipitated apatite crystals that resemble in composition and crystallinity to the mineral phase of bone. The bone regeneration capacity of this synthetic biomimetic calcium phosphate (SBCP) was studied by using an original model of vertical bone regeneration with cups on the calvaria of rats. After 4 weeks, a significantly higher bone growth was found with SBCP compared with deproteinized bovine bone matrix and empty controls. This rapid vertical bone regeneration indicated that this new biomaterial is particularly interesting for filling bone defects in oral surgery.

Bioceramics and bone healing.

Calcium phosphates have long been used as synthetic bone grafts. Recent studies have shown that the modulation of composition and textural properties, such as nano-, micro- and macro-porosity, is a powerful strategy to control and synchronize material resorption and bone formation.Biomimetic calcium phosphates, which closely mimic the composition and structure of bone mineral, can be produced using low-temperature processing routes, and offer the possibility to modulate the material properties to a larger extent than conventional high temperature sintering processes.Advanced technologies open up new possibilities in the design of bioceramics for bone regeneration; 3D-printing technologies, in combination with the development of hybrid materials with enhanced mechanical properties, supported by finite element modelling tools, are expected to enable the design and fabrication of mechanically competent patient-specific bone grafts.The association of ions, drugs and cells allows leveraging of the osteogenic potential of bioceramic scaffolds in compromised clinical situations, where the intrinsic bone regeneration potential is impaired. Cite this article: EFORT Open Rev 2018;3 DOI: 10.1302/2058-5241.3.170056.

Changes in the drug release pattern of fresh and set simvastatin-loaded brushite cement.

Calcium phosphate cements are synthetic bone graft substitutes able to set at physiological conditions. They can be applied by minimally invasive surgery and can also be used as drug delivery systems. Consequently, the drug release pattern from the cement paste (fresh cement) is of high clinical interest. However, previous studies have commonly evaluated the drug release using pre-set cements only. Therefore, the aim of this work was to determine if the time elapsed from cement preparation until immersion in the solution (3 min for fresh cements, and 1h and 15 h for pre-set cements) had an influence on its physical properties, and correlating these to the drug release profile. Simvastatin was selected as a model drug, while brushite cement was used as drug carrier. This study quantified how the setting of a material reduces the accessibility of the release media to the material, thus preventing drug release. A shift in the drug release pattern was observed, from a burst-release for fresh cements to a sustained release for pre-set cements.

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

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.

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.

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.