Personalized lattice-structured prosthesis as a graftless solution for mandible reconstruction and prosthetic restoration: A finite element analysis.

Oral cavity tumors are a prevalent cause of mandible reconstruction surgeries. The mandible is vital for functions like oralization, respiration, mastication, and deglutition. Current mandible reconstruction methods have low success rates due to complications like plate fracture or exposure, infections, and screw loosening. Autogenous bone grafts are commonly used but carry the risk of donor region morbidity. Despite technological advances, an ideal solution for mandible reconstruction remains elusive. Additive manufacturing in medicine offers personalized prosthetics from patient-specific medical images, allowing for the creation of porous structures with tailored mechanical properties that mimic bone properties. This study compared a commercial reconstruction plate with a lattice-structured personalized prosthesis under different biting and osseointegration conditions using Finite Element Analysis. Patient-specific images were obtained from an individual who underwent mandible reconstruction with a commercial plate and suffered from plate fracture by fatigue after 26 months. Compared to the commercial plate, the maximum von Mises equivalent stress was significantly lowered for the personalized prosthesis, hindering a possible fatigue fracture. The equivalent von Mises strains found in bone were within bone maintenance and remodeling intervals. This work introduces a design that doesn't require grafts for large bone defects and allows for dental prosthesis addition without the need for implants.

Electrical stimulation therapy and rotary jet-spinning scaffold to treat bone defects.

The combination of electrical stimulation (ES) and bone tissue engineering (BTE) has been successful in treatments of bone regeneration. This study evaluated the effects of ES combined with PCL + ß-TCP 5% scaffolds obtained by rotary jet spinning (RJS) in the regeneration of bone defects in the calvaria of Wistar rats. We used 120 animals with induced bone defects divided into 4 groups (n = 30): (C) without treatment; (S) with PCL+ ß-TCP 5% scaffold; (ES) treated with ES (10 µA/5 min); (ES + S) with PCL + ß-TCP 5% scaffold. The ES occurred twice a week during the entire experimental period. Cell viability (in vitro: Days 3 and 7) and histomorphometric, histochemical, and immunohistochemical (in vivo; Days 30, 60, and 90) analysis were performed. In vitro, ES + S increased cell viability after Day 7 of incubation. In vivo, it was observed modulation of inflammatory cells in ES therapy, which also promoted blood vessels proliferation, and increase of collagen. Moreover, ES therapy played a role in osteogenesis by decreasing ligand kappa B nuclear factor-TNFSF11 (RANKL), increasing alkaline phosphatase (ALP), and decreasing the tartarate-resistant acid phosphatase. The combination of ES with RJS scaffolds may be a promising strategy for bone defects regeneration, since the therapy controlled inflammation, favored blood vessels proliferation, and osteogenesis, which are important processes in bone remodeling.

Multiscale stiffness characterisation of both healthy and osteoporotic bone tissue using subject-specific data.

Severe bone fractures are often treated by appending internal fixations. In unhealthy or osteoporotic patients, post-implantation bone fractures can occur due to external impact (e.g. from a fall), day-to-day activities in highly-osteoporotic cases and mismatches in the stiffness of bone and the implant's biomaterial, since this causes stress concentrations. One approach to alleviating this problem is to use biomaterials that closely mimic the effective stiffness of real bone, thereby more seamlessly integrating the fixation. This requires to know the properties target (bone properties) and therefore, it highlights the relevance of the evaluation of the bone's mechanical properties which is impractical via direct measurement. This work presents a methodology (multistage homogenisation) for predicting the anisotropic stiffness of bone given the porosity and mineral fraction, both of which are more readily obtained than the mechanical properties themselves. Unlike previous work we: (i) account for finger-like morphology of the mineral phase at the nanoscale; (ii) use microscopy data to model the osteon geometry and its curvilinear anisotropy at the microscale, and (iii) use data to define the trabecular (microCT) and cortical (microscopy) bone geometries at the mesoscale. The predicts have been shown to agree favourably with experimental data in the literature as well as previous modelling works. The results are summarised in a database containing anisotropic stiffness tensors applicable to a broad range of degrees of bone health (e.g. mineral fractions and mesoscale porosities); thus, this work is a contribution towards being able to design more robust patient-specific bone implants in practice.

Polycaprolactone/Beta-Tricalcium Phosphate Scaffolds Obtained via Rotary Jet-Spinning: in vitro and in vivo Evaluation.

This study aimed to evaluate in vitro and in vivo polymeric membranes obtained by a rotary jet-spinning process for the repair of critical bone defects in the calvaria of Wistar rats, for future use in tissue engineering. Experimental sample collections were performed on the 30, 60 and 90th postoperative days, and the analyses performed were histomorphometric, immunohistochemistry, and western blotting. Reducing inflammatory infiltrate in all groups and experimental periods, angiogenesis on the 30th day did not show any difference between the groups, on the 60th day, 5% polycaprolactone/beta-tricalcium phosphate(PCL/ß-TCP) was high compared to control (C), and on the 90th day, the same group reduced when compared to C and 10% PCL/ß-TCP. The fibroplasia presented oscillations in every segment; on the 30th and 60th day, there was an increase in 5% PCL/ß-TCP, which decreased by the 90th day compared to group C. 10% PCL/ß-TCP decreased compared to C on the 60th and 90th day. The percentage of the collagen area remained high in all groups and all experimental periods. Immunohistochemistry quantifications showed variations in bone metabolism suggesting new bone formation. The 5 and 10% PCL/ß-TCP scaffold were promising for the bone regeneration process because they participated in the modulation of inflammation, angiogenesis, fibroplasia, and collagenosis.

Cell investigation into the biocompatibility of adult human dermal fibroblasts with PCL nanofibers/TiO2 nanotubes on the surface of Ti-30Ta alloy for biomedical applications.

The polymer poly(ε-caprolactone) (PCL) has been used in the biomaterial field for its relatively inexpensive price and suitability for modification. Also, its chemical and biological properties are desirable for biomedical applications. The electrospinning process has been used for producing polymer fibers of PCL due in large part to an increased interest in nanoscale properties and technologies. Moreover, the use of biocompatible polymers for the viability of cell growth is a promising alternative to improve osseointegration. Characterization techniques such as scanning electron microscopy and contact angle were used for analyses of samples. Adult human dermal fibroblasts (neonatal) were utilized to evaluate the biocompatibility of the association of the electrospinning process of the biocompatible polymer (PCL) with TiO2 nanotubes on the Ti-30Ta alloy surface. The results of this study showed a favorable response for adhesion on the surface. This promising material is due to the modulation of the biological response.

Fatty acid is a potential agent for bone tissue induction: In vitro and in vivo approach.

Our hypothesis was to investigate the fatty acid potential as a bone induction factor. In vitro and in vivo studies were performed to evaluate this approach. Oleic acid was used in a 0.5 wt.% concentration. Polycaprolactone was used as the polymeric matrix by combining solvent-casting and particulate-leaching techniques, with a final porosity of 70 wt.%, investigated by SEM images. Contact angle measurements were produced to investigate the influence of oleic acid on polycaprolactone chains. Cell culture was performed using adipocyte-derived stem cells to evaluate biocompatibility and bioactivity properties. In addition, in vivo studies were performed to evaluate the induction potential of oleic acid addition. Adipocyte-derived stem cells were used to provide differentiation after 21 days of culture. Likewise, information were obtained with in vivo data and cellular invagination was observed on both scaffolds (polycaprolactone and polycaprolactone /oleic acid); interestingly, the scaffold with oleic acid addition demonstrated that cellular migrations are not related to the surrounding tissue, indicating bioactive potential. Our hypothesis is that fatty acid may be used as a potential induction factor for bone tissue engineering. The study's findings indicate oleic acid as a possible agent for bone induction, according to data on cell differentiation, proliferation, and migration. Impact statement The biomaterial combined in this study on bone regeneration is innovative and shows promising results in the treatment of bone lesions. Polycaprolactone (PCL) and oleic acid have been studied separately. In this research, we combined biomaterials to assess the stimulus and the speed of bone healing.

Influence of Si substitution on the reactivity of α-tricalcium phosphate.

Silicon substituted calcium phosphates have been widely studied over the last ten years due to their enhanced osteogenic properties. Notwithstanding, the role of silicon on α-TCP reactivity is not clear yet. Therefore, the aim of this work was to evaluate the reactivity and the properties of Si-α-TCP in comparison to α-TCP. Precursor powders have similar properties regarding purity, particle size distribution and specific surface area, which allowed a better comparison of the Si effects on their reactivity and cements properties. Both Si-α-TCP and α-TCP hydrolyzed to a calcium-deficient hydroxyapatite when mixed with water but their conversion rates were different. Si-α-TCP exhibited a slower setting rate than α-TCP, i.e. kSSA for Si-TCP (0.021g·m-2·h-1) was almost four times lower than for α-TCP (0.072g·m-2·h-1). On the other hand, the compressive strength of the CPC resulting from fully reacted Si-α-TCP was significantly higher (12.80±0.38MPa) than that of α-TCP (11.44±0.54MPa), due to the smaller size of the entangled precipitated apatite crystals.

Oleic acid surfactant in polycaprolactone/hydroxyapatite-composites for bone tissue engineering.

Bone substitutes are required to repair osseous defects caused by a number of factors, such as traumas, degenerative diseases, and cancer. Autologous bone grafting is typically used to bridge bone defects, but suffers from chronic pain at the donor-site and limited availability of graft material. Tissue engineering approaches are being investigated as viable alternatives, which ideal scaffold should be biocompatible, biodegradable, and promote cellular interactions and tissue development, need to present proper mechanical and physical properties. In this study, poly(ε-caprolactone) (PCL), oleic acid (OA) and hydroxyapatite (HAp) were used to obtain films whose properties were investigated by contact angle, scanning electron microscopy, atomic force microscopy, tensile mechanical tests, and in vitro tests with U2OS human osteosarcoma cells by direct contact. Our results indicate that by using OA as surfactant/dispersant, it was possible to obtain a homogenous film with HAp. The PCL/OA/Hap sample had twice the roughness of the control (PCL) and a lower contact angle, indicating increased hydrophilicity of the film. Furthermore, mechanical testing showed that the addition of HAp decreased the load at yield point and tensile strength and increased tensile modulus, indicating a more brittle composition vs. PCL matrix. Preliminary cell culture experiments carried out with the films demonstrated that U2OS cells adhered and proliferated on all surfaces. The data demonstrate the improved dispersion of HAp using OA and the important consequences of this addition on the composite, unveiling the potentially of this composition for bone growth support. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1076-1082, 2016.

Paired evaluation of calvarial reconstruction with prototyped titanium implants with and without ceramic coating.

PURPOSE: To investigate the osseointegration properties of prototyped implants with tridimensionally interconnected pores made of the Ti6Al4V alloy and the influence of a thin calcium phosphate coating. METHODS: Bilateral critical size calvarial defects were created in thirty Wistar rats and filled with coated and uncoated implants in a randomized fashion. The animals were kept for 15, 45 and 90 days. Implant mechanical integration was evaluated with a push-out test. Bone-implant interface was analyzed using scanning electron microscopy. RESULTS: The maximum force to produce initial displacement of the implants increased during the study period, reaching values around 100N for both types of implants. Intimate contact between bone and implant was present, with progressive bone growth into the pores. No significant differences were seen between coated and uncoated implants. CONCLUSION: Adequate osseointegration can be achieved in calvarial reconstructions using prototyped Ti6Al4V Implants with the described characteristics of surface and porosity.

Cranial reconstruction: 3D biomodel and custom-built implant created using additive manufacturing.

Additive manufacturing (AM) technology from engineering has helped to achieve several advances in the medical field, particularly as far as fabrication of implants is concerned. The use of AM has made it possible to carry out surgical planning and simulation using a three-dimensional physical model which accurately represents the patient's anatomy. AM technology enables the production of models and implants directly from a 3D virtual model, facilitating surgical procedures and reducing risks. Furthermore, AM has been used to produce implants designed for individual patients in areas of medicine such as craniomaxillofacial surgery, with optimal size, shape and mechanical properties. This work presents AM technologies which were applied to design and fabricate a biomodel and customized implant for the surgical reconstruction of a large cranial defect. A series of computed tomography data was obtained and software was used to extract the cranial geometry. The protocol presented was used to create an anatomic biomodel of the bone defect for surgical planning and, finally, the design and manufacture of the patient-specific implant.

Paired evaluation of calvarial reconstruction with prototyped titanium implants with and without ceramic coating

PURPOSE: To investigate the osseointegration properties of prototyped implants with tridimensionally interconnected pores made of the Ti6Al4V alloy and the influence of a thin calcium phosphate coating. METHODS: Bilateral critical size calvarial defects were created in thirty Wistar rats and filled with coated and uncoated implants in a randomized fashion. The animals were kept for 15, 45 and 90 days. Implant mechanical integration was evaluated with a push-out test. Bone-implant interface was analyzed using scanning electron microscopy. RESULTS: The maximum force to produce initial displacement of the implants increased during the study period, reaching values around 100N for both types of implants. Intimate contact between bone and implant was present, with progressive bone growth into the pores. No significant differences were seen between coated and uncoated implants. CONCLUSION: Adequate osseointegration can be achieved in calvarial reconstructions using prototyped Ti6Al4V Implants with the described characteristics of surface and porosity. .

Novel hybrid membrane of chitosan/poly (ε-caprolactone) for tissue engineering.

We investigated the potential use of 3D hybrid membrane: poly (ε-caprolactone) (PCL) mesh using rotary jet spinning with subsequent chitosan (CH) coating. The morphological examinations by scanning electron microscopy (SEM) were proved the efficiency of this technique on obtaining relative homogeneous PCL fiber mats (15,49±4,1µm), with high surface porosity (1,06±0,41µm) and effective CH coating. The feasibility of rotary jet spinning allowed the solvent evaporation during the process; this fact was verified by differential scanning calorimetry (DSC), indeed also had verified changes in thermal properties on the hybrid membrane, since the present of CH. It was investigated the mechanical properties of the hybrid membrane and CH film, the data were that the samples presents good tensile modulus but low strain at the break. In addition, it was verified the biocompatibility properties in vitro using Vero cells. PCL mesh demonstrated cells more spread vastly in the pore surface, with attachments in between fibers indicating the potential for cell adhesion. The films samples (CH and hybrid membrane) resulted in a cells layer on the surfaces with an intense staining (metachromasy), which is the result of cells more active. The cell counting -5 days of culture- and the MTT assay -21 days of culture- demonstrated that the materials tested proved to be different from the positive control and equal to each other and this fact, in our view, this indicates a satisfactory proliferation. Thus, based on the results here, this novel hybrid membrane provides an attractive material for tissue engineering applications.

In vivo evaluation of centrifugal blood pump for cardiopulmonary bypass-Spiral Pump.

The Spiral Pump (SP), a centrifugal blood pump for cardiopulmonary bypass (CPB), has been developed at the Dante Pazzanese Institute of Cardiology/Adib Jatene Foundation laboratories, with support from Sintegra Company (Pompeia, Brazil). The SP is a disposable pump with an internal rotor-a conically shaped fuse with double entrance threads. This rotor is supported by two ball bearings, attached to a stainless steel shaft fixed to the housing base. Worm gears provide axial motion to the blood column, and the rotational motion of the conically shaped impeller generates a centrifugal pumping effect, improving pump efficiency without increasing hemolysis. In vitro tests were performed to evaluate the SP's hydrodynamic performance, and in vivo experiments were performed to evaluate hemodynamic impact during usual CPB. A commercially available centrifugal blood pump was used as reference. In vivo experiments were conducted in six male pigs weighing between 60 and 90 kg, placed on CPB for 6 h each. Blood samples were collected just before CPB (T0) and after every hour of CPB (T1-T6) for hemolysis determination and laboratory tests (hematological and biochemical). Values of blood pressure, mean flow, pump rotational speed, and corporeal temperature were recorded. Also, ergonomic conditions were recorded: presence of noise, difficulty in removing air bubbles, trouble in installing the pump in the drive module (console), and difficulties in mounting the CPB circuit. Comparing the laboratory and hemolysis results for the SP with those of the reference pump, we can conclude that there is no significant difference between the two devices. In addition, reports made by medical staff and perfusionists described a close similarity between the two devices. During in vivo experiments, the SP maintained blood flow and pressure at physiological levels, consistent with those applied in cardiac surgery with CPB, without presenting any malfunction. Also, the SP needed lower rotational speed to obtain average blood flow and pressure, compared with the reference pump.

Injectable biodegradable polycaprolactone-sebacic acid gels for bone tissue engineering.

Tissue engineering constitutes a promising alternative technology to transplantation medicine by creating viable substitutes for failing tissues or organs. The ability to manipulate and reconstitute tissue function has tremendous clinical implications and will most likely play a key role in cell and gene therapies in the coming years. In the present work, a novel injectable and biodegradable biomaterial is reported that could be injected on the human body with a surgical syringe. The material prepared is a blend of polycaprolactone (PCL), a biodegradable and elastic biomedical polymer, and sebacic acid, a natural polymer part of castor oil with low molecular weight to accelerate the slow degradation rate of PCL. The biocompatibility of the blend was evaluated in vitro and its in vivo behavior was also assessed through subcutaneous and bone implantation in rats to evaluate its tissue-forming ability and degradation rate. The results allowed the conclusion that the gel is biocompatible, promotes the differentiation of mesenchymal stem cells, and presents an adequate degradation rate for use in bone tissue engineering. In vivo the gel blends promoted tissue regeneration and adverse reactions were not observed on subcutaneous and bone implants.

Biocompatibility and biodegradation of polycaprolactone-sebacic acid blended gels.

Tissue engineering aims at creating biological body parts as an alternative for transplanting tissues and organs. A current new approach for such materials consists in injectable biodegradable polymers. Their major advantages are the ability to fill-in defects, easy incorporation of therapeutic agents or cells, and the possibility of minimal invasive surgical procedures. Polycaprolactone (PCL) is a promising biodegradable and elastic biomaterial, with the drawback of low-degradation kinetics in vivo. In this work a biodegradable injectable gel of PCL blended with sebacic acid (SA) was prepared, to improve the degradation rate of the biomaterial. SA is known for its high degradation rate, although in high concentrations it could originate a pH decrease and thus disturb the biocompatibility of PCL. Degradation tests on phosphate buffered saline were carried out using 5% of SA on the blend and the biomaterial stability was evaluated after degradation using differential scanning calorimetry, dynamical mechanical analysis, and scanning electronic microscopy. After degradation the elastic properties of the blend decreased and the material became more crystalline and stiffer, although at a lower extent when compared with pure PCL. The blend also degraded faster with a loss of the crystalline phase on the beginning (30 days), although its thermal and mechanical properties remained comparable with those of the pure material, thus showing that it achieved the intended objectives. After cell assays the PCL-SA gel was shown to be cytocompatible and capable of maintaining high cell viability (over 90%).

Poly(ε-caprolactone) and poly(D,L-lactic acid-co-glycolic acid) scaffolds used in bone tissue engineering prepared by melt compression-particulate leaching method.

Porous bioresorbable polymers have been widely used as scaffolds in tissue engineering. Most of the bioresorbable scaffolds are aliphatic polyesters and the methods employed to prepare the porous morphology may vary. This work describes and evaluates the in vitro degradation of porous and dense scaffolds of poly(ε-caprolactone) (PCL) and poly(D,L-lactic acid-co-glycolic acid) (50/50) (PLGA50) prepared by particulate leaching-melt compression process. Biological evaluation was carried out using osteoblast cell cultures. The results showed an autocatalytic effect on the dense samples. Osteoblasts presented intermediate adhesion and the cell morphology on the surface of these materials was dispersed, which indicated a good interaction of the cells with the surface and the material.

Effects of pH on the electrochemical behaviour of titanium alloys for implant applications.

The electrochemical behaviour of two commercial titanium alloys Ti-6Al-4 V (ASTM F136) and Ti-13Nb-13Zr (ASTM F1713) was investigated in Ringer physiological solution at two pH values (5.5 and 7.0). The corrosion properties were examined by using electrochemical techniques: Potentiodynamic anodic polarization, cyclic polarization and electrochemical impedance spectroscopy (EIS). The electrochemical corrosion properties of both alloys at different conditions were measured in terms of corrosion potential (E (corr)), corrosion current density (i (corr)) and passivation current density (i (pass)). Equivalent electrical circuits were used to modulate EIS data, in order to characterize alloys surface and better understanding the pH effect on the interface alloy/solution.

Glutaraldehyde-treated bovine pericardium: effects of lyophilization on cytotoxicity and residual aldehydes.

This work assesses the effect of lyophilization on the cytotoxicity and residual aldehyde concentration of glutaraldehyde-treated and lyophilized bovine pericardium (group A), comparing it to conventional glutaraldehyde-treated bovine pericardium (group B). Cytotoxicity was measured by incubating a pericardium sample from each group in saline and assessing the eluant's influence on cellular growth. Residual aldehydes were measured by HPLC. Although both groups' eluants exhibited some cytotoxicity, the eluant from group A was less cytotoxic, with a cytotoxicity index (IC50(%)) of 41%. Group B eluants all had marked cytotoxic effects; cell growth was 24.15% of the negative control at the most dilute eluant concentration (6.25%). The mean residual glutaraldehyde level was less in group A than in group B (2.36 +/- 0.11 and 9.90 +/- 3.70 g/l, respectively; n=3, P < 0.05), but residual formaldehyde levels did not differ. These results demonstrate that compared with conventional glutaraldehyde-treated bovine pericardium, lyophilized pericardium is less cytotoxic, with fewer glutaraldehyde residues.

The monomeric formulation optimization of dental composite: mechanical and kinetic studies.

The optimization of the monomer composition, using a polymerization kinetic study and the mechanical behavior study of the composites, was the principal objective of this work. The monomeric mixture analyzed is a part of the composite that has been in development at the University of Campinas, Brazil. Parameters such as initiator, accelerator, and macro-components composition were optimized. The infrared spectroscopy was the analytical technique used in the kinetic study. On the mechanical characterization, the stress strain, flexure stress and its modulus, were the properties analyzed. The dependency between the polymeric reaction and the physical behavior of the composites and the monomer composition was observed and studied. Finally, the monomer optimum composition was determined.

Bioreabsorbable polymer scaffold as temporary meniscal prosthesis.

Menisci have an important role in load bearing, shock absorption, knee joint stability, and joint lubrication. Meniscal lesions and meniscectomy are followed by osteoarthritis in a high percentage of patients. At present, there is no ideal prosthesis for meniscal substitution. In this work, a bioreabsorbable polymer scaffold made of poly(L-lactic acid) (PLLA) and poly(p-dioxanone) (PPD) blend was developed to be used as a temporary meniscal prosthesis to stimulate the formation of an in situ meniscal replication while the scaffold is reabsorbed by the organism. Total meniscectomy of medial meniscus and arthrotomy was made in both back knees of 34 adult New Zealand white rabbits by medial parapatellar incision. The scaffolds were sutured in one of the knees, and other was used as a control. A meniscal replica was developed, suggesting that this material has great potential to be used as a meniscal prosthesis, especially because the new meniscus promoted a significant protection of cartilage, and cartilage degeneration in the control condyles was observed.