A novel implantation model for evaluation of bone healing response to dental implants: the goat iliac crest.

OBJECTIVES: Despite the availability of numerous animal models for testing the biological performance of dental and orthopedic implants, the selection of a suitable model is complex. This paper presents a new model for objective and standardized evaluation of bone responses to implants using the iliac crest in goats. MATERIAL AND METHODS: The feasibility of the iliac crest model regarding anatomy and implant positioning was determined using two cadaveric specimens and the bone structure was evaluated and compared with that of the goat femoral condyle. Additionally, the validity of the model was tested by performing an in vivo study. RESULTS: By means of a rather simple, safe, fast and reproducible surgical procedure, the iliac crest in goats could be approached and allowed the implantation of maximally five dental implants per iliac crest. Because of the bilateral implantation possibility, statistical comparisons between groups on either side of the goat could be performed, resulting in a high statistical power, and hence a reduction in the number of animals required to obtain significant data. CONCLUSIONS: In terms of surgical approach, anatomy and implant positioning, the iliac crest is the preferred model over the femoral condyle model. The iliac crest implantation model is suitable for evaluation of the osteogenic response to bone implant materials and represents a justified and deliberate alternative to the already existing animal models.

Effects of implant geometry, surface properties, and TGF-beta1 on peri-implant bone response: an experimental study in goats.

OBJECTIVES: Despite the high success rates in implantology, the desire to use oral implants in more challenging clinical situations drives the need for continuing refinements in implant design and surface properties. In the present study, the effect of implant geometry on implant bone response was evaluated using two geometrically different implant types, i.e. screw type (St) and push-in type(Pi). Furthermore, the potential beneficial effect of an electrosprayed calcium phosphate (CaP) coating, either or not enriched with the osteoinductive growth factor TGF-beta1, on the osteogenic response was examined. MATERIAL AND METHODS: A total of 54 implants, divided into six groups (n=9), were inserted into the femoral condyles of nine goats. After an implantation period of 12 weeks, retrieved specimens were evaluated histologically and histomorphometrically. Measurements were statistically evaluated using SPSS 14.0 and analyzed using a linear regression model. RESULTS: With respect to implant design, St-implants showed an overall superior biological healing response compared with Pi-implants. Considering surface properties, the deposition of an electrosprayed CaP (2-3 microm) coating onto implants significantly increased the amount of bone-implant contact for both implant types. Additional enrichment of the CaP coating with the osteoinductive growth factor TGF-beta1 did not significantly affect peri-implant bone response. CONCLUSIONS: The results of this study indicate that a substantial improvement of the osteogenic response to titanium implants can be achieved by the deposition of an electrosprayed CaP coating. The enrichment of the coating with 1 microg TGF-beta1 has only a marginal effect.

Cleft palate cells can regenerate a palatal mucosa in vitro.

Cleft palate repair leaves full-thickness mucosal defects on the palate. Healing might be improved by implantation of a mucosal substitute. However, the genetic and phenotypic deviations of cleft palate cells may hamper tissue engineering. The aim of this study was to construct mucosal substitutes from cleft palate cells, and to compare these with substitutes from normal palatal cells, and with native palatal mucosa. Biopsies from the palatal mucosa of eight children with cleft palate and eight age-matched control individuals were taken. Three biopsies of both groups were processed for (immuno)histochemistry; 5 were used to culture mucosal substitutes. Histology showed that the substitutes from cleft-palate and non-cleft-palate cells were comparable, but the number of cell layers was less than in native palatal mucosa. All epithelial layers in native palatal mucosa and mucosal substitutes expressed the cytokeratins 5, 10, and 16, and the proliferation marker Ki67. Heparan sulphate and decorin were present in the basal membrane and the underlying connective tissue, respectively. We conclude that mucosal cells from children with cleft palate can regenerate an oral mucosa in vitro.

Orthotopic bone formation in titanium fiber mesh loaded with platelet-rich plasma and placed in segmental defects.

The effect of platelet-rich plasma (PRP) on bone formation was investigated in a rabbit segmental radial defect model. The purpose of the study was to evaluate the bone inductive properties of PRP with titanium fiber mesh and autologous bone chips in a 15-mm rabbit radial defect model. Eighteen New Zealand white rabbits were divided into three groups: I, PRP with autologous bone (PRP-Ti-Bone); II, autologous bone (Ti-Bone); III, control group (Ti). The implants were placed in the radial defect for 12 weeks. After sacrifice, all specimens were harvested for histological, histomorphometrical and radiographic analysis. Histomorphometrical analysis showed that bone formation was higher in the implants with PRP (PRP-Ti-Bone: 37+/-8%) than in those without PRP (Ti-bone: 25+/-6% and Ti: 25+/-5%) after 12 weeks of implantation. It was concluded that PRP has a stimulatory effect on bone formation in titanium fiber mesh filled with autologous bone graft in segmental bone defects. Titanium fiber mesh was also shown to be an excellent scaffold material for the application of autologous bone grafts with or without PRP.

Closing capacity of cranial bone defects using porous calcium phosphate cement implants in a rabbit animal model.

Calcium phosphate (Ca-P) cement is a well established material for bone repair. The bone biological properties of Ca-P cement can even be further improved by creating porosity in the material. The current study aimed on the evaluation of the osteoconductive behavior of porous Ca-P cement. Therefore, circular defects (6, 9, and 15 mm in diameter) were created in the cranium of 3 months old rabbits and filled with porous Ca-P cement implants. The total porosity of implants was calculated to be 71, 74 and 74% respectively and the average pore diameter was 150 microm. In addition, empty control defects were prepared. After 12 weeks implantation time the animals were sacrificed and radiographic, histological, and histomorphometrical evaluation was performed. The Critical Size Defect (CSD) of this species at this location for an implantation time of 12 weeks was confirmed to be 15 mm. Bone was observed to be present over and through almost all porous Ca-P cement implants. Only, in one out of eight animals with a 15 mm implant complete bone bridging of the defect did not occur. The size of the defect was found not to affect the total percentage of bone formation in the cement; (17 +/- 7)%, (18 +/- 6)% and (17 +/- 3)% for respectively 6, 9, and 15 mm diameter implants. We concluded that porous Ca-P cement is an excellent osteoconductive material in non weight bearing situations and complete bridging of a critical sized skull defect occurs in this rabbit model after 12 weeks of implantation.

Influence of RGD-loaded titanium implants on bone formation in vivo.

Little is known about the ability of peptide-coated surfaces to influence cell responses in vivo. Many studies have demonstrated that peptide-modified surfaces influence cell responses in vitro. Integrins, which bind specifically short peptide sequences, are responsible for these cell responses. In this way, information can be transmitted to the nucleus through several cytoplasmic signaling pathways. The peptide sequence Arg-Gly-Asp (RGD peptide) plays an important role in osteoblast adhesion. The present study was designed to investigate new bone formation in a porous titanium (Ti) fiber mesh implant, which was coated with cyclic RGD peptide. The RGD-Ti implants were inserted into the cranium of a rabbit and were compared with porous titanium fiber mesh disks without RGD sequence (Ti) and with an open control defect. Histologic and histomorphometric examinations were performed 2, 4, and 8 weeks postoperatively. A significant increase in bone formation, or bone ingrowth, was seen in the RGD-Ti group compared with the Ti group after 4 and 8 weeks. All control defects stayed open in all three periods. It was concluded that the use of cyclic RGD peptide in combination with titanium fiber mesh has a positive effect on bone formation in vivo in a rabbit animal model.

Controlled release of rhBMP-2 loaded poly(dl-lactic-co-glycolic acid)/calcium phosphate cement composites in vivo.

The release kinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded poly(dl-lactic-co-glycolic acid)/calcium phosphate cement (PLGA/Ca-P cement) composites were studied in vivo. RhBMP-2 was radiolabeled with (131)I and entrapped within PLGA microparticles or adsorbed onto the microparticle surface. PLGA microparticles were prepared of high molecular weight (HMW) PLGA (weight average molecular weight [M(w)] 49,100+/-1700) or low molecular weight (LMW) PLGA (M(w) 5,900+/-300) and used for preparation of 30:70 wt.% PLGA/Ca-P cement composite discs. Release of 131I-rhBMP-2 loaded composites was assessed by scintigraphic imaging according to a 2(2) two-level full factorial design in the rat ectopic model during four weeks. In vivo release kinetics varied among formulations. All formulations showed slow release without initial burst, and displayed a linear release from 3 to 28 days. Release of LMW entrapped rhBMP-2 composites (1.7+/-0.3%/day) was significantly faster than release from other formulations (p<0.01). After 28 days, retention within the composites was 65+/-5%, 75+/-4%, 50+/-4% and 70+/-6% of the initial rhBMP-2 for HMW entrapped, HMW adsorbed, LMW entrapped and LMW adsorbed rhBMP-2 composites, respectively. Release from the composite was probably slowed down by an interaction of rhBMP-2 and Ca-P cement after rhBMP-2 release from PLGA microparticles. We conclude that PLGA/Ca-P cement composites can be considered as sustained slow release vehicles and that the release and retention of rhBMP-2 can be modified according to the desired profile to a limited extent.

The oncological implications of immediate breast reconstruction.

AIMS: The timing of breast reconstruction following mastectomy has been an area of contention. The purpose of this study was to report the oncologic safety of mastectomy and immediate breast reconstruction, primarily with a tissue expander. METHODS: We offered 54 patients (58 reconstructions) an immediate breast reconstruction after a modified radical mastectomy was done for invasive breast cancer. RESULTS: Fifty-eight mastectomies were done for an invasive cancer. Thirteen out of 54 women suffered relapse of their cancer and nine patients died of their disease during the follow-up period. Only in one patient a local recurrence was detected at an early stage and treated without removal of the prosthesis. Disease free survival for all patients was 93% at 5 years. CONCLUSION: Immediate breast reconstruction after mastectomy is an oncologically safe approach and represents a clear improvement in the quality of life for patients with breast cancer. Thus this procedure can safely be offered to appropriately selected women.

Bone formation in CaP-coated and noncoated titanium fiber mesh.

The osteogenic activity of calcium phosphate (CaP)-coated and noncoated porous titanium (Ti) fiber mesh loaded with cultured syngeneic osteogenic cells after prolonged in situ culturing was compared in a syngeneic rat ectopic assay model. Rat bone marrow (RBM) cells were loaded onto the CaP-coated and noncoated Ti scaffolds using either a droplet or a suspension loading method. After loading, the RBM cells were cultured for 8 days in vitro. Thereafter, implants were subcutaneously placed in 39 syngeneic rats. The rats were euthanized and the implants retrieved at 2, 4, and 8 weeks postoperatively. Further, in the 8 week group fluorochrome bone markers were injected at 2, 4, and 6 weeks. Histological analysis demonstrated that only the CaP-coated meshes supported bone formation. The amount of newly formed bone varied between single and multiple spheres to filling a significant part of the mesh porosity. In the newly formed bone, osteocytes embedded in a mineralized matrix could be observed clearly. On the other hand, in the noncoated titanium implants, abundant deposition of calcium-containing material was seen. This deposit lacked a bonelike tissue organization. Further analysis revealed that the cell-loading method did not influence the final amount of bone formation. In CaP-coated implants the accumulation sequence of the fluorochrome markers showed that bone formation started on the mesh fibers. In conclusion, our results prove that the combination of a thin CaP coating, Ti-mesh, and RBM cells can indeed generate ectopic bone formation after prolonged in vitro culturing. No effect of the loading method was observed on the final amount of bone.

The dynamics of interlip coupling in speakers with a repaired unilateral cleft-lip history.

In this paper, data are presented on individual movement characteristics of the upper and lower lip and on interlip coordination in speakers with a repaired unilateral cleft upper lip history and age-matched control participants. The data were acquired using the AG100 EMMA system while the participants produced a selection of nonspeech and speech tasks. The participants with a repaired unilateral cleft upper lip history showed reduced upper-lip movement ranges and peak velocities and a more variable spatiotemporal pattern for individual upper-lip movement cycles, in addition to a more variable interlip coupling. The latter difference also proved to be more pronounced for the younger speakers with a repaired cleft upper lip. Overall, for both groups, the linguistically more complex task showed more variability in the individual upper- and lower-lip movement cycles and their coupling. In the discussion, we address the potential relationships between the kinematic data for upper lip in the repaired-cleft-lip speakers and the findings on movement and coordination stability as they might fit within current notions of coordination dynamics theory.

Subchondral bone mineral density patterns representing the loading history of the wrist joint.

Ten cadaver wrists were examined with CT-Absorptiometry in order to assess bone density in the subchondral bone. In normal wrists the distal radius contained two centroids of bone density, one in the lunate fossa and another in the scaphoid fossa. Pathologically altered wrists showed a shift in bone density towards the scaphoid fossa, with the subchondral bone in the lunate fossa and distal ulna becoming less dense. Bone density patterns in the wrist reflect the long-term force transmission. As bone density alters according to loading conditions, this method can be used to determine force transmission patterns before and after wrist surgery.

[Haemangiomas and congenital vascular malformations: their classification and diagnosis]. / Hemangiomen en congenitale vasculaire malformaties; classificatie en diagnostiek.

Mulliken and Glowacki's classification of peripheral blood- and lymph-vessel abnormalities is based on their clinical course and cellular characteristics, and is therefore clear to and readily usable by the practising physician. In order to make the diagnostic process more accessible, the Haemangiomas and Congenital Vascular Malformations Nijmegen working group has developed a system of diagnostic guidelines on the basis of this classification. The anamnesis should be directed at the following six distinguishing characteristics: presence of the anomaly at birth, growth, involution, change in volume, pain and outflow. The physical examination is directed at the following five characteristics: the possibility of emptying or pushing aside the anomaly, changes in volume during engorgement, murmur/'thrill'/pulsation, phleboliths, and hyper- or hypotrophy. If a diagnosis still cannot be made, then additional investigations may be carried out. Duplex scanning is usually sufficient for this purpose, after which the nature and extent of the malformation can be determined with MRI. On the basis of the results, the persons involved can be informed as to the prognosis of the malformation and a plan of treatment can be proposed.

The treatment of soft-tissue defects of the lower leg after a traumatic open tibial fracture.

The treatment of large soft-tissue defects of the lower leg remains a challenge. The timing of the operation, the most suitable type of tissue, and the decision between local or free flap coverage still remains under discussion. Fifty-two patients were treated with local or free flap coverage after a traumatic soft-tissue defect of the lower leg. We compared the results after treatment with local versus free flaps and fasciocutaneous flaps versus musculocutaneous flaps. In the case of primary reconstruction, we also compared the results regarding the timing of the operation: patients treated within 72 h after the trauma versus patients treated after 72 h. Thirty-five patients (67%) have been treated because of posttraumatic soft-tissue defects and, therefore, insufficient fracture coverage. Seventeen patients (33%) were treated because of a chronic osteomyelitis that arose after the trauma. In our study, we did not find a statistically significant difference between the postoperative complications of local and free flaps. A significant increase could be demonstrated in the number of revisions after treatment with a free flap. Treatment with a fasciocutaneous flap in the entire study group was associated with significantly more postoperative complications than treatment with a musculocutaneous flap. There was no significant difference in results after early or late flap coverage. Patients treated with local or free flaps achieved equal outcomes, except for the number of postoperative revisions in which local flaps required lesser revisions. Treatment with a musculocutaneous flap is preferable to treatment with a fasciocutaneous flap regarding postoperative complications. The timing of operation proved not to be a discriminating factor.

Pedicled prelaminated capsular flaps for coverage of skin defect in a rat model.

SUMMARY: In reconstructive surgery defects are closed using pedicled or free flaps. By raising these flaps the reconstructive surgeon creates new defects, which in turn are closed primarily or with the use of skin grafts. Inevitably, this results in extra scars that may be visible and may also lead to diminished function. In an attempt to avoid full-thickness donor site skin defects in reconstructive surgery, the principle of prefabrication has been modified to produce capsular flaps. In a rat model, we created prefabricated and prelaminated pedicled capsular flaps to fill a full-thickness skin defect. Both femoral vascular bundles in 10 Wistar rats were sandwiched between two silicone sheets. The capsule formed between the two sheets received its main blood supply from this vascular pedicle, and was used as carrier for a skin graft. After ligation of the distal femoral vessels a pedicled prelaminated capsular flap was raised on the proximal femoral vessels. The flap was brought to the surface for closure of an experimentally created abdominal skin defect. All 20 flaps survived, and there were no surgery-related complications. Comparison with controls indicated that flap survival was attributable to the blood supply from the vascular axis. Pedicled prelaminated capsular flaps can be created reliably and reproducibly, confirming the results of earlier studies, and are of value in reconstructive surgery.

Influence of controlled hypotension versus normotension on amount of blood loss during breast reduction.

SUMMARY: Controlled hypotension employed during surgical procedures results in a beneficial reduction in blood loss during the operation. Breast reduction is a common cosmetic surgical procedure. Yet, in the Netherlands, controlled hypotension is not standard during breast reduction procedures, and in fact is only occasionally employed. Our research aimed to establish a set of guidelines which would outline the application of controlled hypotension during breast reduction surgery. The set up of the study was prospective. The patients were randomised into two groups. In the test group, controlled hypotension with an average of 30% reduction in systolic tension was established during the first operative phase. For the control group, normotension was maintained during the entire procedure. The blood loss in the test group (n=23; mean 318 cc) was reduced by 54.1% compared to control (n=28; mean 598 cc), and this difference was significant. A significant positive correlation was also found between blood loss and total incision time. An overall complication rate of 5.1% was observed; however, there was no significant difference between the two groups. A trend in favour of hypotension does suggest it may also help reduce postoperative complications. Our data indicate that a reduction in blood loss of more than 50% can be achieved by employing controlled hypotension in the first operative phase of breast reduction. A reduction in systolic pressure of 20-25% with the use of nitroprusside is sufficient to achieve this reduced blood loss.

Surgeons underestimate their patients' desire for preoperative information.

BACKGROUND: Provision of adequate patient information may contribute to a "satisfying" surgical treatment. The patient's views on successful transfer of information concerning operative characteristics may not be in concert with the surgeon's. The aim of the present study was to determine opinions of both surgeons and patients about issues of surgical information. METHODS: A group of surgeons (n = 24) and surgical patients (n = 125) responded to a questionnaire that included 80 topics involving domains of information on disease, physical examination, preoperative period, anesthesia, operation, postoperative period, self care, and general hospital issues. Both groups were asked for their opinion on what they considered important and useful preoperative information for patients. Questions were scored with a visual analog scale. The reliability of the questionnaire was calculated with Cronbach's alpha. Differences in opinions between surgeons and patients were analyzed with Student's t-test. RESULTS: The Cronbach's alpha of the questionnaire was high (0.91), indicating its high reliability. Patients scored significantly higher (p < 0.001) in most domains, including preoperative period, anaesthesia, operation, postoperative period, self care, and general hospital information. Women demonstrated a significantly higher need for information than men did. These findings were independent of patient age or complexity of operation. In contrast, surgeons thought that their patients desired more extensive information on cause, effect, and prognosis of the disease itself (p < 0.001). CONCLUSION: Surgeons generally underestimate their patients' desire for receiving extensive information prior to a surgical procedure of any complexity. Surgeons should develop strategies to bridge this informational mismatch.

Formation of a reliable capsular flap in a rat model.

UNLABELLED: Prefabrication can be used to produce capsular flaps; other researchers have confirmed the feasibility of such flaps. Before the possibilities of capsular flaps can be explored, a reliable method to create these flaps has to be established first. METHODS: To produce capsular flaps in a rat model, the femoral vascular bundle was sandwiched between two silicone sheets. Three different methods were used and described. The capsule that formed between the two silicone sheets receives its main blood supply from that vascular pedicle. In this way pedicled capsular flaps were created. These flaps were used as a carrier for a skin graft, thus pre-laminating them, to test their ability for reconstructive surgery. The results of the three different methods of creating capsular flaps in a rat model were described and their results were evaluated. Especially the amount of capsule formation and the viability of the skin grafts was observed and compared. The feasibility of pre-laminated capsular flaps is confirmed and the most reliable method of creating them is described.

Guideline proposal to reconstructive surgery for complex perineal sinus or rectal fistula.

AIM: To evaluate a guideline approach of reconstructive surgery for complex perineal sinus or rectal fistula. METHODS: pre-, per-, and postoperative data of 28 patients undergoing transposition of rectus abdominis muscle (TRAM), gracilis muscle (GM), gluteal thigh flap (GTF), or omentoplasty (OP) for complex perineal sinus or rectal fistula were analyzed. A fistula higher than 10 cm and a sinus with a length of >10 cm were treated with TRAM or OP. If <8 cm, the first choice was GM or GTF. The operative team made choice between 8 and 10 cm. Vacuum assisted closure (VAC) therapy was used as adjunct therapy before and after muscle transposition in huge sinus. Success was defined as no residual or recurrent sinus or fistula within 6 months, postoperatively. Long-term complaints of perineum and muscle donor site were assessed. RESULTS: Twenty-five out of 28 patients (90%) were treated according to the guideline. VAC therapy was done in six. Three patients died during mean follow up of 40 months (6-90). Initial success rate was 61% (17/28). After secondary surgery in seven, four (57%) were successful. Overall success rate, including VAC therapy, was 79% (22/28). Success was highest with GM and GTF and in small sinus or fistula. CONCLUSION: A guideline approach to complex perineal sinus or fistula based on length or height of the sinus or rectal fistula, respectively, is successful in about 80% of cases. Large defects may best be downsized by VAC therapy, followed by muscle flap. Long-term complaints are acceptable.

The influence of a PHI-5-loaded silicone membrane, on cutaneous wound healing in vivo.

This study investigated whether a novel ionogenic substance, containing amongst others zinc and rubidium (PHI-5; Dermagenics Inc, Memphis, TN, USA), could improve the healing of full-thickness skin wounds. Uniform wounds were created on the right flank of guinea pigs. Micro-grooved silicone rubber membranes, containing 0 (controls), 1.25, 5.00, or 10.00 microg PHI-5, were sutured onto this wound. Standardized digital wound photographs were made after 1, 3, and 6 weeks. Also, wound biopsies were taken after 3 and 6 weeks for histological and histomorphometrical evaluation. For all study groups, 6 animals were used. Analysis of the 1-week digital photographs showed that the surface area of the wounds decreased significantly, with an increasing PHI-5 concentration. No other differences were found in the wound photographs. Also, no differences were measured in histomorphometry at 3 and 6 weeks. Concluding, in our study model a single application of PHI-5 did have a significant positive influence on initial wound healing.