Preservation of human heart valves for replacement in children with heart valve disease: past, present and future.

Valvular heart disease affects 30% of the new-borns with congenital heart disease. Valve replacement of semilunar valves by mechanical, bioprosthetic or donor allograft valves is the main treatment approach. However, none of the replacements provides a viable valve that can grow and/or adapt with the growth of the child leading to re-operation throughout life. In this study, we review the impact of donor valve preservation on moving towards a more viable valve alternative for valve replacements in children or young adults.

In vivo acid etching effect on bacteria within caries-affected dentin.

Acid etching procedures may disrupt residual bacteria and contribute to the success of incomplete caries removal followed by adhesive restoration. This study evaluated the in vivo effect of acid etching on cariogenic bacterial activity within affected dentin after minimally invasive treatment of caries lesions. Twenty-eight carious permanent teeth received standardized selective caries removal and random acid etch treatment (E) or not (NE) prior to adhesive restoration. Baseline and 3-month dentin biopsies were collected. The number of bacteria and activity of total bacterial cells and Streptococcus mutans were determined by quantitative PCR and RT-PCR. No statistically significant differences were observed in total bacterial number and activity between E and NE treatments (p > 0.3008). For NE, however, the residual S. mutans bacterial cells were reduced (p = 0.0027), while the activity per cell was significantly increased (p = 0.0010) after reentry at 3 months after restoration. This effect was not observed in group E. Although no significant differences were found between groups, this study suggests that acid etching of affected dentin prior to adhesive restoration may directly or indirectly have an inhibitive effect on the activity of residual cariogenic bacteria. Further research is required to investigate this potential effect.

Efficacy of Proximal Resin Infiltration on Caries Inhibition: Results from a 3-Year Randomized Controlled Clinical Trial.

This study reports 3-y outcomes of a split-mouth randomized clinical trial. Resin infiltration's capacity to arrest caries lesion progression in noncavitated proximal lesions is affirmed. Forty-two consented young adults, blinded to tooth surface allocation, were treated with resin infiltration on 1 randomly selected surface and concurrently experienced a mock infiltration procedure on another. Both treatments were provided as an adjunct to the currently accepted standard-of-care regimen (periodic prophylaxis and serial fluoride varnish applications) appropriate for the management of high caries risk. Challenging periods of low oral hygiene compliance were expected. The primary outcome measure was 3-y radiographic lesion progression. Blinded investigators evaluated each study surface for lesion progression with a series of images obtained at intervals over the 3-y course of study. Proportions of progressing lesions were compared with McNemar's test. Twenty-nine noncavitated lesion pairs in permanent posterior teeth demonstrating caries penetrating into inner enamel or outer dentin were included in the analyses. No adverse events were reported. Radiographic progression was recorded in 4 of 29 infiltrated lesions (14%) and 14 of 29 control lesions (48%, P < .003). Adjunct resin infiltration demonstrated a high 3-y efficacy of 71% (relative risk reduction). The prevented fraction was 86% for infiltration versus 52% for controls. Resin infiltration was 100% successful in arresting caries progression in inner enamel lesions (E2) and 64% in outer dentin lesions (D1). Supplementary microinvasive resin infiltration is significantly more efficacious in reducing proximal lesion progression than management by standard noninvasive therapy alone. Long-term results may shed light on whether this represents the arrest or delay of the caries disease process (ClinicalTrials.gov NCT01584024).

Polymeric system for dual growth factor delivery.

The development of tissues and organs is typically driven by the action of a number of growth factors. However, efforts to regenerate tissues (e.g., bone, blood vessels) typically rely on the delivery of single factors, and this may partially explain the limited clinical utility of many current approaches. One constraint on delivering appropriate combinations of factors is a lack of delivery vehicles that allow for a localized and controlled delivery of more than a single factor. We report a new polymeric system that allows for the tissue-specific delivery of two or more growth factors, with controlled dose and rate of delivery. The utility of this system was investigated in the context of therapeutic angiogenesis. We now demonstrate that dual delivery of vascular endothelial growth factor (VEGF)-165 and platelet-derived growth factor (PDGF)-BB, each with distinct kinetics, from a single, structural polymer scaffold results in the rapid formation of a mature vascular network. This is the first report of a vehicle capable of delivery of multiple angiogenic factors with distinct kinetics, and these results clearly indicate the importance of multiple growth factor action in tissue regeneration and engineering.

Decrease in inflammatory hyperalgesia by herpes vector-mediated knockdown of Nav1.7 sodium channels in primary afferents.

Induction of peripheral inflammation increases the expression of the Nav1.7 sodium channel in sensory neurons, potentially increasing their excitability. Peripheral inflammation also produces hyperalgesia in humans and an increase in nociceptive responsiveness in animals. To test the relationship between these two phenomena we applied a recombinant herpes simplex-based vector to the hindpaw skin of mice, which encoded both green fluorescent protein (GFP) as well as an antisense sequence to the Nav1.7 gene. The hindpaw was subsequently injected with complete Freund's adjuvant to induce robust inflammation. Application of the vector, but not a control vector encoding only GFP, prevented an increase in Nav1.7 expression in GFP-positive neurons and prevented development of hyperalgesia in both C and Adelta thermonociceptive tests. These results provide clear evidence of the involvement of an increased expression of the Nav1.7 channel in nociceptive neurons in the development of inflammatory hyperalgesia.

Peripheral and central p38 MAPK mediates capsaicin-induced hyperalgesia.

The stress-activated mitogen-activated protein kinase (MAPK) p38 is emerging as an important mediator of pain. The present study examined the possible involvement of peripheral and spinal p38 MAPK in capsaicin-induced thermal hyperalgesia. Topical capsaicin produced phosphorylation of p38 MAPK in the skin from the affected hindpaw as well as the corresponding lumbar spinal cord in a time dependent manner. Topical capsaicin produced robust C-fiber mediated thermal hyperalgesia that was inhibited by systemic, local peripheral, or central intrathecal pre-treatment with the p38 MAPK inhibitor, SD-282. Intraperitoneal SD-282 (10-60 mg/kg) significantly and dose-dependently attenuated capsaicin-induced C-fiber mediated thermal hyperalgesia. Similarly, 0.1-5mg/kg subcutaneous SD-282 in the hindpaw dose-dependently attenuated capsaicin-induced thermal hyperalgesia. Intrathecal administration of 1microg SD-282 was also anti-hyperalgesic in this model. Functionally, SD-282 decreased capsaicin-induced release of calcitonin gene related peptide in an in vitro skin release assay, consistent with a role for p38 MAPK in peripheral nerve function. These results suggest that p38 MAPK plays a role in the development of hyperalgesic states, exerting effects both centrally in the spinal cord and peripherally in sensory C fibers.

Sustained release of vascular endothelial growth factor from mineralized poly(lactide-co-glycolide) scaffolds for tissue engineering.

Strategies to engineer bone tissue have focused on either: (1) the use of scaffolds for osteogenic cell transplantation or as conductive substrates for guided bone regeneration; or (2) release of inductive bioactive factors from these scaffold materials. This study describes an approach to add an inductive component to an osteoconductive scaffold for bone tissue engineering. We report the release of bioactive vascular endothelial growth factor (VEGF) from a mineralized, porous, degradable polymer scaffold. Three dimensional, porous scaffolds of the copolymer 85 : 15 poly(lactide-co-glycolide) were fabricated by including the growth factor into a gas foaming/particulate leaching process. The scaffold was then mineralized via incubation in a simulated body fluid. Growth of a bone-like mineral film on the inner pore surfaces of the porous scaffold is confirmed by mass increase measurements and quantification of phosphate content within scaffolds. Release of 125I-labeled VEGF was tracked over a 15 day period to determine release kinetics from the mineralized scaffolds. Sustained release from the mineralized scaffolds was achieved, and growth of the mineral film had only a minor effect on the release kinetics from the scaffolds. The VEGF released from the mineralized and non-mineralized scaffolds was over 70% active for up to 12 days following mineralization treatment, and the growth of mineral had little effect on total scaffold porosity.

Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery.

Engineering new tissues utilizing cell transplantation on biodegradable polymer matrices is an attractive approach to treat patients suffering from the loss or dysfunction of a number of tissues and organs. The matrices must maintain structural integrity during the process of tissue formation, and promote the vascularization of the developing tissue. A number of molecules (angiogenic factors) have been identified that promote the formation of new vascular beds from endothelial cells present within tissues, and the localized, controlled delivery of these factors from a matrix may allow an enhanced vascularization of engineered tissues. We have developed a gas foaming polymer processing approach that allows the fabrication of three-dimensional porous matrices from bioabsorbable materials (e.g., copolymers of lactide and glycolide [PLG]) without the use of organic solvents or high temperatures. The effects of several processing parameters (e.g., gas type, polymer composition and molecular weight) on the process were studied. Several gases (CO(2), N(2), He) were utilized in the fabrication process, but only CO(2) resulted in the formation of highly porous, structurally intact matrices. Crystalline polymers (polylactide and polyglycolide) did not form porous matrices, while amorphous copolymers (50:50, 75:25, and 85:15 ratio of lactide:glycolide) foamed to yield matrices with porosity up to 95%. The mechanical properties of matrices were also regulated by the choice of PLG composition and molecular weight. Angiogenic factors (e.g., vascular endothelial growth factor) were subsequently incorporated into matrices during the fabrication process, and released in a controlled manner. Importantly, the released growth factor retains over 90% of its bioactivity. In summary, a promising system for the incorporation and delivery of angiogenic factors from three-dimensional, biodegradable polymer matrices has been developed, and the fabrication process allows incorporation under mild conditions.

Distributed crack analysis of ceramic inlays.

In all-ceramic restorations, crack formation and propagation phenomena are of major concern, since they may result in intra-oral fracture. The objective of this study was calculation of damage in porcelain MOD inlays by utilization of a finite-element (FE) implementation of the distributed crack theory. "Damage" is defined as the parameter that describes the local decrease of stiffness caused by microdefects. In the simulated MOD ceramic inlay, the crack initiation starts at the internal occlusal surface near the pulpo-axial line angle. This initiation is invisible from the external surface and cannot be detected by the clinician. The crack initiation at the internal surface started as soon as 55-60% of the loading needed for complete fracture was reached. The use of FE techniques for calculation of the fracture in loaded ceramic inlays offers prospects for further detailed study of the crack behavior, including three-dimensional modeling and cyclic loading situations.

Fracture-mechanics parameters of the composite-enamel bond.

In a previous study, the critical values of the opening mode stress intensity factor (K1), its equivalent, the strain energy-release rate (G1), and the J integral (J1) (in the elastic case being equal to that of G1) were determined for resin composite. In this study, the strength of the composite-tooth interface was investigated. The critical values of K1 and J1 were measured with single-edge notched-bend (SENB) specimens of resin composite bonded to enamel, with the notch at midspan at the bonded interface. Due to enamel's anisotropy, the values of Klc and Jlc to be used in a fracture-mechanics application for failure prediction of a structure depend on the enamel prism orientation relative to the adhesive interface. Where interfacial failure is to be expected, the following values for Jlc and Klc can be used: Silux, Jlc = 145 +/- 35 Jm-2 and Klc = 0.84 +/- 0.16 MNm-3/2; P-30, Jlc = 163 +/- 13 Jm-2 and Klc = 1.02 +/- 0.07 MNm-3/2. Where enamel failure is expected or where the failure mode cannot be predicted, the following values can be applied: Silux, Jlc = 89 +/- 15 Jm-2 and Klc = 0.84 +/- 0.16 MNm-3/2; P-30, Jlc = 89 +/- 15 Jm-2 and Klc = 0.75 +/- 0.10 MNm-3/2.

Verification of theoretical modeling of heat transmission in teeth by in vivo experiments.

A theoretical axisymmetric tooth model, simulating the conditions involved in the drinking of a liquid of a certain temperature, was compared with results of a similar in vivo experiment. The temperature changes as a result of one draught of a hot/cold liquid were recorded within the model as well as in the surrounding environment. The experimental data obtained were compared with the calculated results for the theoretical model as determined by the Finite Element Analysis. The temperatures recorded experimentally agreed reasonably with the calculated results. It can be concluded that the assumptions which have been made concerning the described thermal loading conditions lead to a good approximation of the physical reality.

Fracture mechanics parameters for failure prediction of composite resins.

This study contains the first part of a research project in which the applicability of fracture mechanics parameters to predict failure of a restored tooth was investigated. Fracture mechanics parameters have been used in dental research before, but were restricted to comparative studies between various brands of composites. The critical values of the opening mode stress intensity factor (KI), its equivalents, the strain energy release rate (GI), and the J integral (JI), were measured with single-edge notched-bend (SENB) specimens of dental composite in a three-point bend test. The measured values of KIc for Silux (KIc = 0.99 +/- 0.03 MNm-3/2) and P-30 (KIc = 1.88 +/- 0.12 MNm-3/2), compared with values from the literature, show quantitative agreement. The J integral was computed by means of finite element analysis (FEA) on a two-dimensional model of the SENB specimens. The critical value of the J integral (measured with SENB specimens, notch depth-to-width ratio (a/W) = 1/2) was used to predict failure of specimens having an arbitrary geometry. In this study, failure was predicted for SENB specimens with notch depth-to-width ratio (a/W) = 1/4 and 3/4. The predicted deflection and load at failure correspond well with the measured deflection and load.

The influence of modification of cavity design on distribution of stresses in a restored molar.

In this study, two different cavity designs were compared from a mechanical point of view: (a) an axisymmetric model of a conventional class 1 cavity preparation and restoration; and (b) an axisymmetric model of a modified cavity design. The modified design was characterized by a cavo-surface angle (c.s.a.) of approximately 90 degrees and a stepped cavity wall. Using a mathematical model, stresses were calculated by finite element analysis to compare the force distribution. It is concluded that the clinical superiority of the modified cavity design, with respect to the marginal breakdown of the amalgam restoration, can be supported by stress calculations.

Stress analysis of a tooth restored with a post and core.

An idealized axisymmetric finite element model of a second premolar restored with a post and core was used to study the distribution and magnitude of stresses as a function of the following parameters: the diameter of the post, the length and the shape of the post, and finally the interface characteristics between post and cement. Emphasis was directed toward the cement layer interposed between the post and the tooth. Bonding between the post and the cement appeared to be the most important parameter to achieve optimal mechanical behavior of the tooth-prosthesis combination.

Failure stress criteria for composite resin.

In previous work (Peters and Poort, 1983), the stress distribution in axisymmetric models of restored teeth was analyzed by finite element analysis (FEA). To compare the tri-axial stress state at different sites, they calculated the Von Mises equivalent stress and used it as an indication for weak sites. However, the use of Von Mises' theory for material failure requires that the compressive and tensile strengths be equal, whereas for composite resin the compressive strength values are, on the average, eight times larger than the tensile strength values. The objective of this study was to investigate the applicability of a modified Von Mises and the Drücker-Prager criterion to describe mechanical failure of composite resin. In these criteria, the difference between compressive and tensile strength is accounted for. The stress criteria applied to an uni-axial tensile stress state are compared with those applied to a tri-axial tensile stress state. The uni-axial state is obtained in a Rectangular Bar (RB) specimen and the tri-axial state in a Single-edge Notched Bend (SENB) specimen with a chevron notch at midspan. Both types of specimens, made of light-cured composite, were fractured in a three-point bend test. The size of the specimens was limited to 16 mm x 2 mm x 2 mm (span, 12 mm). Load-deflection curves were recorded and used for linear elastic FEA. The results showed that the Drücker-Prager criterion is a more suitable criterion for describing failure of composite resins due to multi-axial stress states than are the Von Mises criterion and the modified Von Mises criterion.

The influence of restorative dental materials on heat transmission in human teeth.

Using the finite element method, we analyzed the temperature distribution and heat flow patterns in an axisymmetric tooth model. The models of an unrestored tooth and three teeth restored with different restorative materials were evaluated comparatively. The insulating ability of a calcium hydroxide cement base (Ca(OH)2) is low, which is inherent in its insufficient thermal and poor mechanical properties. In the given conditions, the Ca(OH)2 base reduces the temperature increase at the cement-dentin interface by 12.5% with respect to a restoration of amalgam only. By using a double base (Ca(OH)2 + polymer-modified zinc oxide-eugenol), the reduction is 21.9%. With respect to a sound tooth model, the presence of a double base in the restored tooth caused a temperature increase of only 0.1 degree C at the pulpo-dentinal junction. The thermal conductivity coefficient (lambda) of amalgam does not have any influence on the results of the calculations. The heat transfer coefficient (alpha) turned out to be an essential parameter in this mathematical model.

Aging affects two modes of nanoleakage expression in bonded dentin.

Water sorption into resin-dentin interfaces precedes hydrolytic degradation. We hypothesized that these processes are morphologically manifested by the uptake of ammoniacal silver nitrate, which is thought to trace hydrophilic domains and water-filled channels within matrices. Water sorption is thought to be nonuniform and can be traced by the use of silver nitrate. Human teeth bonded with an experimental filled-adhesive were aged in artificial saliva (experimental) or non-aqueous mineral oil (control). Specimens retrieved for up to a 12-month period were immersed in 50 wt% ammoniacal silver nitrate and examined by transmission electron microscopy for identification of the changes in their silver uptake. Reticular silver deposits initially identified within the bulk of hybrid layers in the experimental group were gradually reduced over time, but were subsequently replaced by similar deposits that were located along the hybrid layer-adhesive interface. Silver uptake in water-binding domains of the adhesive layers increased with aging, resulting in water tree formation. These water-filled channels may act as potential sites for hydrolytic degradation of resin-dentin bonds.

Fatigue behavior of direct post-and-core-restored premolars.

Evaluation of long-term mechanical behavior of new types of restorations in clinical trials is time-consuming. A partial alternative can be found in experimental fatigue-testing, which simulates accelerated mechanical deterioration. The aim of this study was to determine the feasibility of using fatigue-testing of a complex dental restoration and to evaluate the mechanical fatigue behavior of premolar teeth restored with a titanium alloy post and an amalgam or composite core. Eighty-seven human upper premolar teeth were decoronated, embedded, and restored with a prefabricated post of 1 mm diameter. The teeth were randomly assigned to one of two groups corresponding with a core build-up of amalgam or chemically-cured core composite, respectively. Five to 21 days after restoration, the specimens were subjected to cyclic loading (frequency, 5 Hz), at an angle of 45 degrees to the long axis of the tooth. The boundary technique was used for determination of the mean fatigue strengths of the restorations at 10(4), 10(5), and 10(6) cycles, simulating up to 1-3 years of clinical functioning. Mean fatigue strength was expressed in percentage of initial strength: For 10(4), 10(5), and 10(6) cycles, the results were 66%, 58%, and 52%, respectively, for the amalgam and 62%, 62%, and 53% for the composite group. It is concluded that fatigue-testing of more complex systems is possible, if a suitable testing method is selected. The restorations showed a comparable strength reduction after 10(6) cycles of about 50% of their initial strength. The composite core build-up showed a behavior less predictable than that of the amalgam, which might be attributed to handling parameters.

Development of technologies aiding large-tissue engineering.

There are many clinical situations in which a large tissue mass is required to replace tissue lost to surgical resection (e.g., mastectomy). It is possible that autologous cell transplantation on biodegradable polymer matrices may provide a new therapy to engineer large tissue which can be used to treat these patients. A number of challenges must be met to engineer a large soft tissue mass. These include the design of (1) a structural framework to maintain a space for tissue development, (2) a space-filling matrix which provides for localization of transplanted cells, and (3) a strategy to enhance vascularization of the forming tissue. In this paper we provide an overview of several technologies which are under development to address these issues. Specifically, support matrices to maintain a space for tissue development have been fabricated from polymers of lactide and glycolide. The ability of these structures to resist compressive forces was regulated by the ratio of lactide to glycolide in the polymer. Smooth muscle cell seeding onto polyglycolide fiber-based matrices has been optimized to allow formation of new tissues in vitro and in vivo. Finally, polymer microsphere drug delivery technology is being developed to release vascular endothelial growth factor (VEGF), a potent angiogenic molecule, at the site of tissue formation. This strategy, which combines several different technologies, may ultimately allow for the engineering of large soft tissues.

Estimation of the mechanical lifetime of dental restorations: method and preliminary results.

To assess the clinical performance of restorative materials with respect to mechanical failure, the shape of the restoration, the strength and fatigue properties and the loading history are important. This study deals with the feasibility of a method to estimate the mechanical lifetime of dental restorations. The method takes into account that the mechanical lifetime is a stochastic quantity determined by shape, strength and fatigue properties and by the cyclic nature of the mastication forces. The general outline of the method is described and the necessary experimental data are discussed. Preliminary estimates of the lifetime of a composite and an amalgam restoration are made. The method is found to be feasible and the estimated lifetimes of the restoration are of the same order of magnitude as found clinically.