Effect of enamel matrix derivative and parathyroid hormone on bone formation in standardized osseous defects: an experimental study in minipigs

Previous experimental studies have indicated that locally administered enamel matrix derivative (EMD) and parathyroid hormone (PTH) may have a stimulatory effect on bone formation. However, it is not clear if the positive effect of EMD is related to its effect on the periodontium as a whole or directly on the bone-forming cells. In addition, it is not known if the presentation of PTH by adding the amino acid sequence Arg-Gly-Asp (RGD) is essential for its osteopromotive effect. Local delivery of a bioactive substance at the right time and in the right concentration often constitutes a major challenge. Polyethylene glycol-based hydrogel (PEG) is a degradable vehicle developed for delivery of bioactive proteins. To enhance the mechanical stability of the PEG-bioactive substance complex, an osteoconductive bone substitute material is often needed.

Intraoperative Patient-Specific Reconstruction of Partial Bone Flap Defects After Convexity Meningioma Resection

OBJECTIVE: To evaluate implant accuracy and cosmetic outcome of a new intraoperative patient-specific cranioplasty method after convexity meningioma resection. METHODS: The patient's own bone flap served as a template to mold a negative form with the use of polymethyl methacrylate (PMMA). The area of bone invasion was determined and broadly excised under white light illumination with a safety margin of at least 1 cm. The definitive replica was cast within the remaining bone flap frame and the imprint. Clinical and radiologic follow-up examinations were performed 3 months after surgery. RESULTS: Four women and two men (mean age 51.4 years ± 12.8) underwent reconstruction of bone flap defects after meningioma resection. Mean duration of intraoperative reconstruction of the partial bone flap defects was 19 minutes ± 4 (range 14-24 minutes). Implant sizes ranged from 17-35 cm(2) (mean size 22 cm(2) ± 8). Radiologic and clinical follow-up examinations revealed excellent implant alignment and favorable cosmesis (visual analogue scale for cosmesis [VASC] = 97 ± 5) in all patients. CONCLUSIONS: Patient-specific reconstruction of partial bone flap defects after convexity meningioma resection using the presented intraoperative PMMA cast method resulted in excellent bony alignment and a favorable cosmetic outcome. Relatively low costs and minimized operation time for adjustment and insertion of the cranioplasty implant justify use of this method in small bony defects as well.

The transposition advancement flap for repair of postsurgical defects on the upper lip

Skin cancer of the lip is frequent, and reconstruction after Mohs surgery might be challenging mostly when the postsurgical defect has a size of more than 1 cm(2) and is situated adjacent to the philtrum.

Detection of Internal Defects in Concrete Members Using Global Vibration Characteristics

Rock-pocket and honeycomb defects impair overall stiffness, accelerate aging, reduce service life, and cause structural problems in hardened concrete members. Traditional methods for detecting such deficient volumes involve visual observations or localized nondestructive methods, which are labor-intensive, time-consuming, highly sensitive to test conditions, and require knowledge of and accessibility to defect locations. The authors propose a vibration response-based nondestructive technique that combines experimental and numerical methodologies for use in identifying the location and severity of internal defects of concrete members. The experimental component entails collecting mode shape curvatures from laboratory beam specimens with size-controlled rock pocket and honeycomb defects, and the numerical component entails simulating beam vibration response through a finite element (FE) model parameterized with three defect-identifying variables indicating location (x, coordinate along the beam length) and severity of damage (alpha, stiffness reduction and beta, mass reduction). Defects are detected by comparing the FE model predictions to experimental measurements and inferring the low number of defect-identifying variables. This method is particularly well-suited for rapid and cost-effective quality assurance for precast concrete members and for inspecting concrete members with simple geometric forms.

Electrospun PLLA nanofiber scaffolds and their use in combination with BMP-2 for reconstruction of bone defects

Introduction Adequate migration and differentiation of mesenchymal stem cells is essential for regeneration of large bone defects. To achieve this, modern graft materials are becoming increasingly important. Among them, electrospun nanofiber scaffolds are a promising approach, because of their high physical porosity and potential to mimic the extracellular matrix (ECM). Materials and Methods The objective of the present study was to examine the impact of electrospun PLLA nanofiber scaffolds on bone formation in vivo, using a critical size rat calvarial defect model. In addition we analyzed whether direct incorporation of bone morphogenetic protein 2 (BMP-2) into nanofibers could enhance the osteoinductivity of the scaffolds. Two critical size calvarial defects (5 mm) were created in the parietal bones of adult male Sprague-Dawley rats. Defects were either (1) left unfilled, or treated with (2) bovine spongiosa, (3) PLLA scaffolds alone or (4) PLLA/BMP-2 scaffolds. Cranial CT-scans were taken at fixed intervals in vivo. Specimens obtained after euthanasia were processed for histology, histomorphometry and immunostaining (Osteocalcin, BMP-2 and Smad5). Results PLLA scaffolds were well colonized with cells after implantation, but only showed marginal ossification. PLLA/BMP-2 scaffolds showed much better bone regeneration and several ossification foci were observed throughout the defect. PLLA/BMP-2 scaffolds also stimulated significantly faster bone regeneration during the first eight weeks compared to bovine spongiosa. However, no significant differences between these two scaffolds could be observed after twelve weeks. Expression of osteogenic marker proteins in PLLA/BMP-2 scaffolds continuously increased throughout the observation period. After twelve weeks osteocalcin, BMP-2 and Smad5 were all significantly higher in the PLLA/BMP-2 group than in all other groups. Conclusion Electrospun PLLA nanofibers facilitate colonization of bone defects, while their use in combination with BMP-2 also increases bone regeneration in vivo and thus combines osteoconductivity of the scaffold with the ability to maintain an adequate osteogenic stimulus.

Funduscopy in adult zebrafish and its application to isolate mutant strains with ocular defects

Funduscopy is one of the most commonly used diagnostic tools in the ophthalmic practice, allowing for a ready assessment of pathological changes in the retinal vasculature and the outer retina. This non-invasive technique has so far been rarely used in animal model for ophthalmic diseases, albeit its potential as a screening assay in genetic screens. The zebrafish (Danio rerio) is well suited for such genetic screens for ocular alterations. Therefore we developed funduscopy in adult zebrafish and employed it as a screening tool to find alterations in the anterior segment and the fundus of the eye of genetically modified adult animals.A stereomicroscope with coaxial reflected light illumination was used to obtain fundus color images of the zebrafish. In order to find lens and retinal alterations, a pilot screen of 299 families of the F3 generation of ENU-treated adult zebrafish was carried out.Images of the fundus of the eye and the anterior segment can be rapidly obtained and be used to identify alterations in genetically modified animals. A number of putative mutants with cataracts, defects in the cornea, eye pigmentation, ocular vessels and retina were identified. This easily implemented method can also be used to obtain fundus images from rodent retinas.In summary, we present funduscopy as a valuable tool to analyse ocular abnormalities in adult zebrafish and other small animal models. A proof of principle screen identified a number of putative mutants, making funduscopy based screens in zebrafish feasible.

Four-year results following treatment of intrabony periodontal defects with an enamel matrix derivative alone or combined with a biphasic calcium phosphate

The aim of this study was to evaluate the 4-year clinical outcomes following regenerative surgery in intrabony defects with either EMD + BCP or EMD. Twenty-four patients with advanced chronic periodontitis, displaying one-, two-, or three-walled intrabony defect with a probing depth of at least 6 mm, were randomly treated with either EMD + BCP (test) or EMD alone (control). The following clinical parameters were evaluated at baseline, at 1 year and at 4 years after regenerative surgery: plaque index, gingival index, bleeding on probing, probing depth, gingival recession, and clinical attachment level (CAL). The primary outcome variable was CAL. No differences in any of the investigated parameters were observed at baseline between the two groups. The test group demonstrated a mean CAL change from from 10.8 ± 1.6 mm to 7.4 ± 1.6 mm (p < 0.001) and to 7.6 ± 1.7 mm (p < 0.001) at 1 and 4 years, respectively. In the control group, mean CAL changed from 10.4 ± 1.3 at baseline to 6.9 ± 1.0 mm (p < 0.001) at 1 year and 7.2 ± 1.2 mm (p < 0.001) at 4 years. At 4 years, two defects in the test group and three defects in the control group have lost 1 mm of the CAL gained at 1 year. Compared to baseline, at 4 years, a CAL gain of ≥3 mm was measured in 67% of the defects (i.e., in 8 out of 12) in the test group and in 75% of the defects (i.e., in 9 out of 12) in the control group. There were no statistically significant differences in any of the investigated parameters at 1 and at 4 years between the two groups. Within their limits, the present results indicate that: (a) the clinical improvements obtained with both treatments can be maintained over a period of 4 years, and (b) in two- and three-walled intrabony defects, the addition of BCP did not additionally improve the outcomes obtained with EMD alone. In two- and three-walled intrabony defects, the combination of EMD + BCP did not show any advantage over the use of EMD alone.

Wound healing following regenerative procedures in furcation degree III defects: histomorphometric outcomes

Degree III furcation involvements were surgically created at four first molars in each of three monkeys. Following 6 weeks of healing, full-thickness flaps were elevated. Following 24% EDTA gel conditioning, the defects were treated with one of the following: (1) enamel matrix proteins (EMD), (2) guided tissue regeneration (GTR) or (3) a combination EMD and GTR. The control defects did not receive any treatment. After 5 months of healing, the animals were sacrificed. Three 8 μm thick histological central sections, 100 μm apart, were used for histomorphometric analysis in six zones of each tooth either within the furcation area or on the pristine external surface of the root. In all specimens, new cementum with inserting collagen fibres was formed. Following GTR or GTR + EMD, cementum was formed up to and including the furcation fornix indicating complete regeneration on the defect periphery. Periodontal ligament fibres were less in all four modalities compared to pristine tissues. In the teeth treated with GTR and GTR + EMD a higher volume of bone and periodontal ligament tissues was observed compared to EMD. After 5 months of healing, regenerated tissues presented quantitative differences from the pristine tissues. In the two modalities where GTR alone or combined with EMD was used, the regenerated tissues differed in quantity from the EMD-treated sites.

Reconstruction of large supra-eyebrow and forehead defects using the hatchet flap principle and sparing sensory nerve branches

To reconstruct a forehead defect, a plastic surgeon must be knowledgeable about the neural, vascular, and muscular anatomy. The position of fixed structures such as eyebrows and hairline should be respected. For the past 5 years, we have used double hatchet flaps for reconstruction of relatively large supra-eyebrow and forehead defects. Because this flap does not appear to be among the techniques used by young plastic surgeons, we thought that it would be valuable to report our experience.

Repair of superficial osteochondral defects with an autologous scaffold-free cartilage construct in a caprine model: implantation method and short-term results

OBJECTIVE: To compare four different implantation modalities for the repair of superficial osteochondral defects in a caprine model using autologous, scaffold-free, engineered cartilage constructs, and to describe the short-term outcome of successfully implanted constructs. METHODS: Scaffold-free, autologous cartilage constructs were implanted within superficial osteochondral defects created in the stifle joints of nine adult goats. The implants were distributed between four 6-mm-diameter superficial osteochondral defects created in the trochlea femoris and secured in the defect using a covering periosteal flap (PF) alone or in combination with adhesives (platelet-rich plasma (PRP) or fibrin), or using PRP alone. Eight weeks after implantation surgery, the animals were killed. The defect sites were excised and subjected to macroscopic and histopathologic analyses. RESULTS: At 8 weeks, implants that had been held in place exclusively with a PF were well integrated both laterally and basally. The repair tissue manifested an architecture similar to that of hyaline articular cartilage. However, most of the implants that had been glued in place in the absence of a PF were lost during the initial 4-week phase of restricted joint movement. The use of human fibrin glue (FG) led to massive cell infiltration of the subchondral bone. CONCLUSIONS: The implantation of autologous, scaffold-free, engineered cartilage constructs might best be performed beneath a PF without the use of tissue adhesives. Successfully implanted constructs showed hyaline-like characteristics in adult goats within 2 months. Long-term animal studies and pilot clinical trials are now needed to evaluate the efficacy of this treatment strategy.

An in vivo study of a growth-factor enhanced, cell free, two-layered collagen-tricalcium phosphate in deep osteochondral defects

Focal osteochondral defects are still a challenging problem in joint surgery. We have developed a two-layered implant consisting of a basal porous beta-tricalcium phosphate (TCP) for bone reconstruction and a superficial fibrous collagen type I/III layer for cartilage regeneration. Fifty-four osteochondral defects in the trochlear groove of 27 Göttinger Minipigs were created and either left untreated, treated with the implant alone, or the implant augmented with an additional growth factor mixture, which was assumed to stimulate cell and tissue differentiation. Follow-up was 6, 12 and 52 weeks with n=6 for each group. The repair tissue was evaluated for its gross appearance and biomechanical properties. Histological sections were semi-quantitatively scored for their histomorphological structure. Treatment with the two-layered implant improved defect filling and subchondral bone repair at 6 and 12 weeks follow-up. The TCP was replaced by cancellous bone at 52 weeks. Cartilage repair tissue mainly consisted of fibrocartilage and showed a moderate cell density up to the joint surface. Growth factor treatment improved the mechanical and histomorphological properties of the cartilage repair tissue at 12, but not at 52 weeks postoperatively. In conclusion, the two-layered collagen-TCP implant augmented with chondroinductive growth factors seems a promising new option for the treatment of deep osteochondral defects in joint surgery.