The Jugaad Technique for Jaw Reconstruction: Denture Based Inverse Planning.

AIM: The aim of this clinical paper is to introduce a technique to plan for functional maxillofacial reconstructions. MATERIALS AND METHODS: Preoperative dental casts were made of the patient and mock surgery performed on the casts. A fibula analogue was then placed in an ideal functional reconstruction position. New dentures were fabricated on the fibula analogue and drill holes for the placement of implants were placed through the denture. This denture formed as a guide to position the fibula transplant during surgery. RESULTS: This technique was useful in producing functional and rehabilitative outcomes in cases of both maxillary and mandibular reconstructive surgeries. CONCLUSION: The Jugaad technique-denture based inverse planning-is a cost effective method for planning and executing maxillofacial reconstructions using mock surgery on casts and interim dentures.

A bar-retained overdenture as an external fixator device in a three-dimensional CAD/CAM-based surgical reconstruction of the mandible.

Large defects of the human face often cause esthetic as well as functional disorders. We present a new technique for reconstruction of the mandible with prosthodontic rehabilitation in a single surgery, using the implant-supported, bar-retained overdenture as an external fixator. A 58-year-old patient presented with a near total defect of the mandible after cancer resection. For rehabilitation, the mandibular condyles were virtually positioned in the centre of the fossae, and four dental implants were planned. The position of the fibula segments as well as their angulation and lengths were adapted to the implant position. To transfer this plan into surgery, a combined cutting/implant drilling guide was computer-aided printed. To provide the correct angulation of the fibula segments, a CAD/CAM dental arch-bar was made from titanium, fulfilling three functions: to bear the provisional prosthesis; to stabilize the molded fibula as an external fixator; and to position the complete fibula with the prosthesis in a correct relation to the upper jaw and occlusion, as indicated by the prosthesis. This innovative approach of combined prosthodontic and reconstructive rehabilitation could shorten the total reconstruction/rehabilitation time and avoid the need for additional extended surgeries.

Comparing calvarial transport distraction with and without radiation and fat grafting.

The purpose of this study is to: a) assess transport distraction to reconstruct cranial defects in radiated and non-radiated fields b) examine adipose grafting's effect on the bony regenerate and overlying wound, and c) elucidate sources of bone formation during transport distraction osteogenesis. Twenty-three male New Zealand white rabbits (3 months; 3.5 kg) were used, 10 non-irradiated and 13 irradiated (17 treatment, 6 control) with a one-time fraction of 35 Gy. A 16 × 16 mm defect was abutted by a 10 × 16 mm transport disc 5 weeks after irradiation, and 11 animals were fat grafted at the distraction site. Latency (1 day), distraction (1.5 mm/day), and consolidation (4 weeks) followed. Fluorochromes were injected subcutaneously and microCT, fluorescence, and histology assessed. In distracted animals without fat grafting, bone density measured 701.87 mgHA/ccm and 2271.95 mgHA/ccm in irradiated and non-irradiated animals. In distracted animals with fat grafting, bone density measured 703.23 mgHA/ccm and 2254.27 mgHA/ccm in irradiated and non-irradiated animals. Fluorescence revealed ossification emanating from the dura, periosteum, and transport segment with decreased formation in irradiated animals. Transport distraction is possible for cranial reconstruction in irradiated fields but short-term osseous fill is significantly diminished. Adipose grafting enhances wound healing in previously irradiated fields but does not enhance ossification.

Evaluation of cranial bone transport distraction with and without adipose grafting.

Transport distraction osteogenesis (DO) can be used to autologously reconstitute calvarial defects. The purpose of this study is to histomorphologically interrogate osteogenic formation during cranial transport distraction using a novel device. We also evaluate the effect of fat grafting on the regenerate and soft-tissue stability during distraction. This study was approved by Yale IACUC. Ten male New Zealand white rabbits (3 mo; 3.5 kg) were used (8 treatment, 2 control). A 16 × 16 mm defect was created abutted by a 10 × 16 mm transport disc. The device was fixated anterioposteriorly. Four animals were fat-grafted using 2 mL of subdermal intrascapular fat deposited along the distraction site. Latency (1 d), active distraction (12-14 d) (1.5 mm/d), and consolidation (4 wk) followed. Calcein and xylene orange fluorochromes were injected subcutaneously during and post-distraction to mark sites of bone formation. Following sacrifice, osteogenesis was assessed using microCT, histology, and fluorescence. Treatment animals demonstrated regenerate bone between distracted segments on microCT. MicroCT analysis of non-fat-grafted and fat-grafted animals revealed a mean density of 2271.95 mgHA/ccm and 2254.27 mgHA/ccm (P = 0.967), respectively, and defect bone versus total volume (BV/TV) of 0.0999 and 0.0766 (P = 0.5979), respectively. Controls had minimal reossification. Histologically, mean densities measured 43.63% and 8.19%, respectively. Fluorescence revealed ossification from the callus as well as from dura and periosteum in the cranial defect. Transport distraction is effective to reconstruct critically sized rabbit calvarial defects. Regenerate bone arises predominantly from the callus with contribution from surrounding dura and periosteum. Adipose grafting is well tolerated but does not enhance osseous regeneration.

Influence of osteotomy procedure and surgical experience on early complications after orthognathic surgery in the mandible.

INTRODUCTION: This study evaluated the influence of osteotomy procedure and surgical experience on early complication rates following orthognathic surgery in the mandible. MATERIALS AND METHODS: In a retrospective study, patients who underwent a mandibular osteotomy (Obwegeser-Dal Pont (ODP) and Hunsuk-Epker (HE)) were included. Incidence of "bad splits", "bleeding episodes", "delayed wound healing", "failed osteosynthesis" and "nerve lesions" at 2 months post-operatively were recorded. Surgical experience was classified as: beginner (<10), intermediate (10-40) and expert (>40). Complications were correlated to the surgical approach and the experience level of the surgeon. RESULTS: 400 patients were included. 200 underwent a bimaxillary approach. 186 patients were operated using the ODP technique, 214 according to HE. Multivariate analysis confirmed significantly more unwanted fractures and bleeding events for ODP when compared to HE (p = 0.28, p = 0.003). Experienced surgeons had more osteosynthesis failures (0.047) and significantly more nerve lesions than the other groups (p = 0.01). DISCUSSION: The HE osteotomy showed a more reliable fracture mechanism with less relevant bleeding episodes. Differences between the surgeons of varying training status were marginal with exception of a higher rate of osteosynthesis failure and temporary hypoesthesia in the experienced group.

"Fibonacci's route" to regioregular oligo(3-hexylthiophene)s.

We describe a new synthetic approach to regioregular monodisperse oligo(3-alkylthiophene)s allowing for simple separation of regioregular material in gram quantities. The number of repeat units follows the Fibonacci numbers up to a length of 21. In a small adaption of this approach, introduction of a protecting group was used to synthesize an oligo(3-hexylthiophene) with 36 repeating units, the longest regioregular 3-hexylthiophene oligomer synthesized to date.

A general relationship between disorder, aggregation and charge transport in conjugated polymers.

Conjugated polymer chains have many degrees of conformational freedom and interact weakly with each other, resulting in complex microstructures in the solid state. Understanding charge transport in such systems, which have amorphous and ordered phases exhibiting varying degrees of order, has proved difficult owing to the contribution of electronic processes at various length scales. The growing technological appeal of these semiconductors makes such fundamental knowledge extremely important for materials and process design. We propose a unified model of how charge carriers travel in conjugated polymer films. We show that in high-molecular-weight semiconducting polymers the limiting charge transport step is trapping caused by lattice disorder, and that short-range intermolecular aggregation is sufficient for efficient long-range charge transport. This generalization explains the seemingly contradicting high performance of recently reported, poorly ordered polymers and suggests molecular design strategies to further improve the performance of future generations of organic electronic materials.

The influence of bisphosphonates on viability, migration, and apoptosis of human oral keratinocytes--in vitro study.

Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is one of the most often seen side effects in patients treated with bisphosphonates, presenting clinically as a non-healing wound. One theory of BP-ONJ etiology describes a negative effect on soft tissues, especially on keratinocytes, which play an important role in oral wound healing and oral soft tissue regeneration. A high cell viability of keratinocytes, which can migrate to the affected location, is essential for wound healing. The aim of this in vitro study was to investigate the effect of differently potent bisphosphonates on human oral keratinocytes (HOK).Three nitrogen-containing bisphosphonates (ibandronate, pamidronate, and zoledronate) and one non-nitrogen-containing bisphosphonate (clodronate) were compared concerning their potency on cell viability (calcein assay and MTT assay), migration ability (Boyden chamber migration assay and scratch wound proliferation assay), and apoptosis (TUNEL assay) of HOK.The nitrogen-containing bisphosphonates, particularly highly potent pamidronate and zoledronate preparations, had a strong negative influence on cell viability, migration ability, and apoptosis of HOK. The non-nitrogen-containing clodronate even increased cell viability in higher concentrations.This study demonstrates that bisphosphonates have a strong influence on HOK on different cellular levels like cell viability, migration ability, and apoptosis rate. The results support the theory that BP-ONJ is a multifactorially caused disease.Furthermore, this in vitro study confirms the theory that perioperative interruption of bisphosphonate application during dental surgical procedures might be feasible to promote better tissue regeneration and wound healing.

Bone marrow concentrate and bovine bone mineral for sinus floor augmentation: a controlled, randomized, single-blinded clinical and histological trial--per-protocol analysis.

PURPOSE: The purpose of this work was to evaluate the potential of substituting autogenous bone (AB) by bone marrow aspirate concentrate (BMAC). Both AB and BMAC were tested in combination with a bovine bone mineral (BBM) for their ability of new bone formation (NBF) in a multicentric, randomized, controlled, clinical and histological noninferiority trial. MATERIALS AND METHODS: Forty-five severely atrophied maxillary sinus from 26 patients were evaluated in a partial cross-over design. As test arm, 34 sinus of 25 patients were augmented with BBM and BMAC containing mesenchymal stem cells. Eleven control sinus from 11 patients were augmented with a mixture of 70% BBM and 30% AB. Biopsies were obtained after a 3-4-month healing period at time of implant placement and histomorphometrically analyzed for NBF. RESULTS: NBF was 14.3%±1.8% for the control and nonsignificantly lower (12.6%±1.7%) for the test (90% confidence interval: -4.6 to 1.2). Values for BBM (31.3%±2.7%) were significantly higher for the test compared with control (19.3%±2.5%) (p<0.0001). Nonmineralized tissue was lower by 3.3% in the test compared with control (57.6%; p=0.137). CONCLUSIONS: NBF after 3-4 months is equivalent in sinus, augmented with BMAC and BBM or a mixture of AB and BBM. This technique could be an alternative for using autografts to stimulate bone formation.

The influence of bisphosphonates on human osteoblast migration and integrin aVb3/tenascin C gene expression in vitro.

BACKGROUND: Bisphosphonates are therapeutics of bone diseases, such as Paget's disease, multiple myeloma or osteoclastic metastases. As a severe side effect the bisphosphonate induced osteonecrosis of the jaw (BONJ) often requires surgical treatment and is accompanied with a disturbed wound healing.Therefore, the influence on adhesion and migration of human osteoblasts (hOB) after bisphosphonate therapy has been investigated by morphologic as well as gene expression methods. METHODS: By a scratch wound experiment, which measures the reduction of defined cell layer gap, the morphology and migration ability of hOB was evaluated. A test group of hOB, which was stimulated by zoledronate 5 × 10(-5)M, and a control group of unstimulated hOB were applied. Furthermore the gene expression of integrin aVb3 and tenascin C was quantified by Real-Time rtPCR at 5 data points over an experimental period of 14 days. The bisphosphonates zoledronate, ibandronate and clodronate have been compared with an unstimulated hOB control. RESULTS: After initially identical migration and adhesion characteristics, zoledronate inhibited hOB migration after 50 h of stimulation. The integrinavb3 and tenascin C gene expression was effected by bisphosphonates in a cell line dependent manner with decreased, respectively inconsistent gene expression levels over time. The non-nitrogen containing bisphosphonates clodronate led to decreased gene expression levels. CONCLUSION: Bisphosphonates seem to inhibit hOB adhesion and migration. The integrin aVb3 and tenascin C gene expression seem to be dependent on the cell line. BONJ could be enhanced by an inhibition of osteoblast adhesion and migration. The gene expression results, however, suggest a cell line dependent effect of bisphosphonates, which could explain the interindividual differences of BONJ incidences.

Amphiphilic, low molecular weight poly(ethylene imine) derivatives with enhanced stability for efficient pulmonary gene delivery.

BACKGROUND: Poly(ethylene imine) (PEI) is a widely used transfection reagent for mammalian cells, but in vivo application of PEI 25 kDa is restricted by its toxicity. Low molecular weight (LMW) PEI is less toxic, but also less efficient than its high molecular weight equivalent, and prone to aggregation. METHOD: A set of polymers was synthesized by coupling poly(ethylene glycol) (PEG) that contained either C(16/18) -chains (Cx-EO) or butyl-poly(propylene oxide)-co-poly(ethylene glycol) (ButPP). Critical micelle concentration (CMC) was determined for copolymers. Polyplexes were characterized by DNA binding ability, polyplex size and aggregation, hemolysis, and cytotoxicity. Transfection efficiency was tested in vitro and in vivo in mouse lungs. RESULTS: Copolymers formed stable complexes with DNA, and showed enhanced complex stability in isotonic solution for at least 1 h. CMC was determined for Cx-EO-PEI 4.7 and 8.3 at 0.0019 and 0.0037 mM, respectively; membrane activity in a haemolysis assay was demonstrated for ButPP-PEI: both factors possibly enhance endosomal escape effect after PEGylation. IC(50) values of all synthesized polymers were in the range 6-33 ng/ml. Transfection efficiency of unmodified LMW-PEIs was equivalent or better than that of PEI 25 as a result of aggregation in vitro. Cells treated with polyplexes of amphiphilic polymers showed reduced transfection compared to PEI 25. After instillation in mouse lungs, highest transfection efficiency was demonstrated with Cx-EO copolymer of lowest molecular weight PEI. CONCLUSIONS: A new set of polymers with low toxicity and high stability was synthesized, which contains promising candidates for pulmonary gene transfer, as documented by in vivo experiments in mice.

Osteonecrosis of the jaw related to sunitinib.

CASE REPORT: A 59-year-old male patient was referred to the hospital with exposed bone measuring 10 mm in diameter in the posterior, left-side region of the lower jaw. Two months previous, the first molar had been extracted. The patient had contracted renal cell carcinoma and had been treated by nephrectomy in 2003. Soft tissue metastases occurred. After initial therapy with interferon and vinblastine, a relapse occurred and the therapy was changed to sorafenib, followed by sunitinib. Osteonecrosis of the lower jaw appeared 1 year after initial and exclusive therapy with sunitinib. CONCLUSIONS: Bisphosphonates had never been applied. With increasing application of multi-kinase inhibitors, complications due to osteonecrosis could occur more frequently.

A prospective, randomized pilot study on the safety and efficacy of recombinant human growth and differentiation factor-5 coated onto ß-tricalcium phosphate for sinus lift augmentation.

OBJECTIVES: The aim of this prospective, randomized clinical trial was to investigate the potential of recombinant human growth and differentiation factor-5 (rhGDF-5) coated onto ß-tricalcium phosphate (ß-TCP) (rhGDF-5/ß-TCP) to support bone formation after sinus lift augmentation. MATERIAL AND METHODS: In total, 31 patients participated in this multicenter clinical trial. They required a two-stage unilateral maxillary sinus floor augmentation (residual bone height <5 mm). According to a parallel-group design, the patients were randomized to three treatment groups: (a) augmentation with rhGDF-5/ß-TCP and a 3-month healing period, (b) augmentation with rhGDF-5/ß-TCP and a 4-month healing period and (c) medical device ß-TCP mixed with autologous bone and a 4-month healing period. The primary study objective was the area of newly formed bone within the augmented area as assessed by histomorphometric evaluation of trephine bur biopsies. RESULTS: The osseous regeneration was similar in each treatment group; the amount of newly formed bone ranged between 28% (± 15.5%) and 31.8% (± 17.9%). Detailed analysis of histological data will be published elsewhere. As secondary efficacy variables, the augmentation height at the surgery site was measured by radiography. The largest augmentation was radiologically achieved in the rhGDF-5/ß-TCP - 3-month and the rhGDF-5/ß-TCP - 4-month treatment groups. As safety parameters, adverse events were recorded and anti-drug antibody levels were evaluated. Most of the adverse events were judged as unrelated to the study medication. Four out of 47 (8.5%) implants failed in patients treated with rhGDF-5/ß-TCP, a result that is in agreement with the general implant failure rate of 5-15%. Transiently very low amounts of anti-rhGDF-5 antibodies were detected in some patients who received rhGDF-5, which was not related to the bone formation outcome. CONCLUSION: rhGDF-5/ß-TCP was found to be effective and safe as the control treatment with autologous bone mixed ß-TCP in sinus floor augmentation. Thus, further investigation regarding efficacy and safety will be carried out in larger patient populations.