A New Technique of Open Septal Reduction Using Polydioxanone Plates for Nasoseptal Fracture: Three-Dimensional Volumetric Analysis.

BACKGROUND: In this study, we designed a new technique for open septal reduction using a polydioxanone (PDS) plate and compared it with closed reduction (CR). METHODS: This study included 19 consecutive patients with nasoseptal fracture: 10 receiving open reduction with a PDS plate (PDS group) and 9 undergoing CR group. Open septal reduction was performed after CR for nasal bone fracture. A mucoperichondrial flap was unilaterally elevated, and the deviated septal cartilage was reduced. The PDS plate was inserted horizontally above the vomerine suture. Surgical outcome was analyzed with three-dimensional volumetry and with a quality-of-life scale for nasal obstruction (Nasal Obstruction Symptom Evaluation scale). RESULTS: Complications included 1 case of septal perforation in the CR group and 1 case of PDS exposure and septal hematoma in the PDS group. In the three-dimensional volumetric analysis of the PDS group, the median value of the nasal cavity change significantly differed between 1.14 mL (interquartile range; 0.46-2.4) at the preoperative computed tomography scan and 0.33 mL (interquartile range; -0.22 to 1.29) at the postoperative computed tomography scan (∗∗P = 0.0039). The Nasal Obstruction Symptom Evaluation scale revealed significant improvement in nasal obstruction postsurgically (median value, 42.5-7.5; ∗P = 0.0139) in the PDS group. CONCLUSIONS: Polydioxanone plates potentially present a new concept of open septal reduction in terms of septal reinforcement compared with the subtractive approach of open septal reduction.

Secondary bone grafting for alveolar clefts: surgical timing, graft materials, and evaluation methods.

Alveolar cleft belongs to the spectrum of cleft lip and/or palate, affecting 75% of cleft lip/palate patients. The goals of alveolar cleft treatment are stabilizing the maxillary arch, separating the nasal and oral cavities, and providing bony support for both erupting teeth and the nasal base via the piriform aperture. Secondary alveolar bone grafting is a well-established treatment option for alveolar cleft. Secondary alveolar bone grafting is performed during the period of mixed dentition using autologous bone from various donor sites. There are several issues relevant to maximizing the success of secondary alveolar bone grafting, including the surgical timing, graft material, and surgical technique. In this study, we reviewed issues related to surgical timing, graft materials, and evaluation methods in secondary alveolar bone grafting. Abbreviations: ABG, alveolar bone grafting; CBCT, cone-beam computed tomography; DBM, demineralized bone matrix; GPP, gingivoperiosteoplasty; rhBMP, recombinant human bone morphogenetic protein; 2D, two dimensional; 3D, three dimensional.

Promotion of dermal tissue engineering in a rat model using a composite 3D-printed scaffold with electrospun nanofibers and recipient-site preconditioning with an external volume expansion device.

We hypothesized that use of a composite three-dimensionally (3D) printed scaffold with electrospun nanofibers in conjunction with recipient-site preconditioning with an external volume expansion (EVE) device would enable successful dermal tissue regeneration of a synthetic polymer scaffold. Cell viability, cell infiltration, extracellular matrix deposition, scaffold contraction, and mRNA expression by dermal fibroblasts cultured on three different scaffolds, namely, 3D-printed scaffold with a collagen coating, 3D-printed scaffold with an electrospun polycaprolactone nanofiber and collagen coating, and 3D-printed scaffold with an electrospun polycaprolactone/collagen nanofiber, were measured. Before scaffold implantation, rats were treated for 2 h with an EVE device to evaluate the effect of this device on the recipient site. Cell proliferation rates were significantly higher on the 3D-printed scaffold with electrospun polycaprolactone nanofiber and collagen coating than on the other scaffolds. In cell invasion studies, the 3D-printed scaffold with electrospun polycaprolactone nanofiber and collagen coating showed better cell integration than the other scaffolds. Under stereomicroscopy, fibroblasts adhered tightly to the electrospun area, and the fibroblasts effectively produced both collagen and elastin. Rat skin treated with an EVE device exhibited increased HIF-1α protein expression and capillary neoformation compared with control skin. Invasion of CD8+ cytotoxic lymphocytes surrounding the scaffold decreased when the recipient site was preconditioned with the EVE device. The composite 3D printed scaffold with electrospun nanofibers provided a favorable environment for proliferation, migration, and extracellular matrix synthesis by fibroblasts. Recipient-site preconditioning with an EVE device allowed for scaffold incorporation with less inflammation due to improved angiogenesis.

Reconstruction of a pathologic fracture following osteomyelitis of the mandible using a fibula osteocutaneous flap.

The use of a fibula osteocutaneous flap is currently the mainstay of segmental mandibular reconstruction. This type of flap is used to treat tumors, trauma, or osteoradionecrosis of the mandible. However, a fibula osteocutaneous flap may also be a good option for reconstructing the mandible to preserve oropharyngeal function and facial appearance in cases of pathological fracture requiring extensive segmental bone resection. Chronic osteomyelitis is one of the various causes of subsequent pathologic mandibular fractures; however, it is rare, and there have been few reports using free flaps in osteomyelitis of the mandible. We share our experience with a 76-year-old patient who presented with a pathologic fracture following osteomyelitis of the mandible that was reconstructed using a fibula osteocutaneous flap after wide segmental resection.

Safety verification for polysorbate 20, pharmaceutical excipient for intramuscular administration, in Sprague-Dawley rats and New Zealand White rabbits.

Human serum albumin (HSA) has been widely used as a pharmaceutical excipient in Botulinum toxin serotype A (BoNT/A) products that are indicated for use in therapeutics and cosmetics. However, HSA as a human-derived material has some concerns, such as the potential risk of transmission of infectious agents, an insufficient supply, and difficulty in maintaining a certain quality. For those reasons, newly developed BoNT/A products (CORETOX®, Medytox, Inc., Republic of Korea) contained polysorbate 20, a non-human-derived excipient, to replace the HSA. However, most safety studies of polysorbate 20 have been conducted with non-invasive routes of administration, and thus there are a few studies on the safety of polysorbate 20 when administered intramuscularly. To secure the in vivo safety profile of polysorbate 20, a four-week repeated intramuscular dose toxicity study (0.02, 0.1, and 0.4 mg/kg, one injection every two weeks for a total of three injections) was conducted in 66 Sprague-Dawley (SD) rats. An intradermal irritation study was further conducted with 18 New Zealand White (NZW) rabbits. The toxicological evaluation of HSA (0.06 and 0.12 mg/kg) was also carried out as a comparative substance. Systemic and local toxicities were not observed in any of the SD rats or NZW rabbits based on clinical signs, body weight, hematology, clinical biochemistry, macroscopic findings on necropsy, histopathology of the injection site, and allergic reactions. The current study suggested that intramuscular administration of polysorbate 20 was considered to be safe at a level similar to that of HSA, which has an in vivo safety profile accumulated over the years. This provided the basis for the in vivo safety profile of polysorbate 20 administered intramuscularly and the scientific reliability of the use of polysorbate 20 as an alternative to HSA, which is used as an excipient for various pharmaceuticals in terms of its safety.

Preparation of Stretchable Nanofibrous Sheets with Sacrificial Coaxial Electrospinning for Treatment of Traumatic Muscle Injury.

Traumatic muscle injury with massive loss of muscle volume requires intramuscular implantation of proper scaffolds for fast and successful recovery. Although many artificial scaffolds effectively accelerate formation and maturation of myotubes, limited studies are showing the therapeutic effect of artificial scaffolds in animal models with massive muscle injury. In this study, improved myotube differentiation is approved on stepwise stretched gelatin nanofibers and applied to damaged muscle recovery in an animal model. The gelatin nanofibers are fabricated by a two-step process composed of co-axial electrospinning of poly(ɛ-caprolactone) and gelatin and subsequent removal of the outer shells. When stepwise stretching is applied to the myoblasts on gelatin nanofibers for five days, enhanced myotube formation and polarized elongation are observed. Animal models with volumetric loss at quadriceps femoris muscles (>50%) are transplanted with the myotubes cultivated on thin and flexible gelatin nanofiber. Treated animals more efficiently recover exercising functions of the leg when myotubes and the gelatin nanofiber are co-implanted at the injury sites. This result suggests that mechanically stimulated myotubes on gelatin nanofiber is therapeutically feasible for the robust recovery of volumetric muscle loss.

DNA aptamer immobilized hydroxyapatite for enhancing angiogenesis and bone regeneration.

In this study, we developed aptamer-conjugated hydroxyapatite (Apt-HA) that promotes bone regeneration and angiogenesis. The 3R02 bivalent aptamer specific to vascular endothelial growth factor (VEGF) was grafted to the hydroxyapatite (HA) surface. Apt-HA was tested for its VEGF protein capture ability to determine the optimal aptamer concentration immobilized on the HA. Apt-HA showed higher VEGF protein capture ability, and faster growth of human umbilical vein endothelial cell (HUVEC) compared to a neat HA with no cytotoxic effects on human osteoblasts. To examine in vivo angiogenesis and bone regeneration, Apt-HA and HA were bilaterally implanted into rabbit tibial metaphyseal defects and analyzed after eight weeks using micro-CT, histology, and histomorphometry. Apt-HA showed significantly increased the volume of new bones, the percentage of bone, and the density of bone mineral in cortical bone. Apt-HA also exhibited the enhanced bone formation at the cortical region in a histomorphometric analysis. Finally, Apt-HA showed significantly increased blood vessel number compared to a neat HA. In summary, the engineered Apt-HA has potential as a bone graft material that may simultaneously promote bone regeneration and angiogenesis. STATEMENT OF SIGNIFICANCE: This work presents a functional hydroxyapatite bone graft using a DNA-based aptamer which overcomes the limitations of existing bone graft materials, which use bound signaling peptides. DNA aptamer immobilized hydroxyapatite enhances the in vitro proliferation of human umbilical vascular endothelial cells as well as in vivo angiogenesis and bone regeneration. DNA aptamer immobilized hydroxyapatite shows no cytotoxic effect on human osteoblasts.

An evaluation of buccal infiltrations and inferior alveolar nerve blocks in pulpal anesthesia for mandibular first molars.

We compared the anesthetic efficacy of inferior alveolar nerve blocks (IANBs) with that of buccal infiltrations (BIs) in mandibular first molars. Using a crossover design, all subjects received a standard IANB or a BI of 1.7 mL of 4% articaine with 1:100,000 adrenaline (Septanest; Septodont, Saint-Maru-des-Fosses, France) on two appointments separated by at least 1 week. Pulpal anesthesia was determined by using an electric pulp tester. Electric pulp testing was repeated at 5, 8, 11, 15, 20, 25, and 30 minutes after the injections. Anesthesia was considered successful if the subject did not respond to the maximum output of the pulp tester at two or more consecutive time points. Fifty-four percent of the BI and 43% of the IANB were successful; the difference was not significant (p = 0.34). The onset of pulpal anesthesia was significantly faster with BI (p = 0.03). In conclusion, BI with 4% articaine for mandibular first molars can be a useful alternative for clinicians because compared with IANB it has a faster onset and a similar success rate.

Repair of rabbit radial bone defects using bone morphogenetic protein-2 combined with 3D porous silk fibroin/ß-tricalcium phosphate hybrid scaffolds.

Our study aimed to investigate the effect of bone morphogenetic protein-2 (BMP-2) bound to silk fibroin and ß-tricalcium phosphate (SF/ß-TCP) hybrid on the healing of critical-size radial defects in rabbits. A 15-mm critical-size defect was induced at mid-diaphysis in the left radius of 20 New Zealand white rabbits (average age, 3.5 months; weight, 2.5-3.0 kg). The animals were randomized into Group 1 (SF/ß-TCP combined with BMP-2), Group 2 (SF/ß-TCP alone), and Group 3 (nothing implanted). Radiographs were obtained every 2 weeks and euthanasia was performed after 8 weeks for visual, radiological, micro-computed tomography (micro-CT), and histological studies. Eight weeks after implantation (SF/ß-TCP combined with BMP-2), radiographs showed that new bone formed on the surface of the implant and had bridged the defect in Group 1. Micro-CT imaging also confirmed the formation of new bone around the implant, and the newly formed bone was quantified. Histological examination revealed newly formed bone in the implanted area. Meanwhile, there was no formation of new bone in Group 3. Among the groups, most active formation of new bones was found in Group 1, while there was no difference between Group 2 and Group 3. Based on these results, we concluded that BMP-2-SF/ß-TCP showed significant improvement in healing of critical-size defects. Therefore, the combination of BMP-2 and SF/ß-TCP would be useful in the field of bone tissue engineering.

Long-term results of secondary alveolar bone grafting using a technique to harvest pure calvarial cancellous bone: Evaluation based on plain radiography and computed tomography.

BACKGROUND: We introduce a method to extract the maximum amount of cancellous bone from the calvarium and analyze the outcomes using plain radiography and computed tomography. METHODS: We retrospectively analyzed the medical records of patients who underwent secondary alveolar bone grafts using a maximal harvesting technique for calvarial cancellous bone. Bone survival was determined based on Enemark's grading system using plain radiographs. Alveolar thickness and height were analyzed by computed tomography and compared with radiographic measurements. RESULTS: Our study enrolled 27 patients, 22 unilateral and 5 bilateral, for a total of 32 alveolar clefts. The mean age at surgery was 9.04 ± 0.41 years (range: 6-12 years). Donor sites were successfully recovered without complications, such as hematomas, seromas, infections, or tears in the dura mater. The mean follow-up duration for obtaining plain radiographs was 6.90 ± 0.61 years (range: 2.0-18.50 years). The mean follow-up duration for computed tomography was 6.51 ± 0.99 years (range: 2.0-14.83 years). A canine tooth erupted in 30 cases. Success (Enemark's grades I or II) was achieved in 26 cases. Alveolar height was strongly correlated with the Enemark scale results (γ = 0.878, p < 0.001), but alveolar thickness was not correlated (γ = 0.4575, p = 0.08). CONCLUSION: Our cancellous bone harvesting technique resulted in successful graft survival without serious complications, including dural or brain injuries. Although the ilium is widely accepted as the optimal donor site for secondary alveolar bone grafting, the calvarium could be an alternative donor site that results in equivalent outcomes.

Co-effect of silk and amniotic membrane for tendon repair.

The objective of the present study was to determine the feasibility and biocompatibility of a silk scaffold and a composite silk scaffold in terms of new tendon generation using a rabbit Achilles tendon model. The silk scaffold was constructed using a weaving machine, then soaked in a 1% collagen-hyaluronan (HA) solution and air-dried, whereas the composite silk scaffold was composed of a silk scaffold containing a lyophilized collagen-HA substrate. Tenocytes were cultured in vitro to compare cell populations in the two groups. The cellular densities on composite silk scaffolds were 40% higher on average than those on silk scaffolds in 30-day tenocyte cultures. The tendon scaffolds had implanted into Achilles tendon defects in 16 white New Zealand rabbits. Rabbits were randomly divided into the following three groups: group I, silk scaffold alone; group II, composite silk scaffold; and group III, composite silk scaffold wrapped by an amniotic membrane. Implants were harvested 2, 8, and 12 weeks post-implantation. Histological examinations were conducted using hematoxylin-eosin (H&E), Masson's trichrome, and by performing immunohistochemical staining for CD34. After 12 weeks, the three groups were distinguishable based on gross examination. The histological examination revealed more organized collagen fibrils in groups III, which showed a dense, parallel, linear organization of collagen bundles. CD34 staining revealed neoangiogenesis in groups III. The results of this research showed that collagen-HA substrates with amniotic membrane accelerate cellular migration and angiogenesis in neotendons.

An anthropometric and three-dimensional computed tomographic evaluation of two-point fixation of zygomatic complex fractures.

BACKGROUND: Maintaining stability and restoring the aesthetic appearance are the fundamental goals when managing zygomatic fractures. We aimed to evaluate the stability and anthropometric outcomes of zygomatic fracture patients who underwent two-point fixation involving the infraorbital rim and zygomaticomaxillary buttress via the transconjunctival and gingivobuccal approaches without any skin incisions. METHODS: We examined 15 zygomatic fracture patients who underwent two-point fixation during a 3-year period. Stability was evaluated using three-dimensional facial bone computed tomography. Superoinferior and anteroposterior displacement of the zygoma was quantified. The aesthetic appearance of the periorbital region was evaluated using indirect anthropometry with standardized clinical photographs. The ratios between the eye fissure height and width, and lower iris coverage ratio were used to evaluate aesthetical changes. The bony displacement and aesthetic ratios were analyzed using Wilcoxon or Friedman tests. The correlation between the preoperative zygoma position and anthropometric values was analyzed. RESULTS: The positions of the zygoma were similar to those on the contralateral side at the long-term follow-up. The preoperative anthropometric measurements on the fractured side differed from those on the contralateral side, although these values were close to the normal values at the long-term follow-up. Furthermore, we noted that the anteroposterior displacement strongly positively correlated with the lower iris coverage rate (Spearman's coefficient= 0.678, P=0.005). CONCLUSIONS: Two-point fixation of zygomatic fractures achieved stable outcomes on long-term follow-up, and also appeared to be reliable in restoring the aesthetic appearance of the periorbital region.