Relative effects of wound healing and mechanical stimulus on early bone response to porous-coated implants

We hypothesized that early bone adaptation to well fixed porous-coated implants is influenced more by wound healing than by mechanical loading. To test this hypothesis, two groups of dogs with identical, hydraulically controlled porous-coated implants interference fit within distal femoral trabecular bone were used. One group had no load: the other had 35 N of load applied to the implants. At 5 weeks after surgery, the resulting adaptation of bone around the implants was quantified on a cellular basis by cytochemical analysis of type-I procollagen synthesis and on a structural basis using three-dimensional micro-computed tomography imaging. The percentage of trabecular surfaces covered by osteoblasts expressing type-I procollagen was significantly increased in bone surrounding the implant in both groups compared with contralateral control bone tissue. There was no difference between the groups with no load or 35 N of load. In addition, measures of trabecular bone structure did not differ significantly between the load and no-load groups. Taken together, these results suggest that wound healing plays a much greater role in the early response of bone to well fixed porous-coated implants than does mechanical stimulus.     

Expression of Wnt genes in early wound healing

The effects of ambient temperature (22 degrees C/10 degrees C) and season (summer/winter) on anuran skin allograft and xenograft rejection was tested in frogs (Rana temporaria and R. esculenta) and toads (Bufo bufo, Bombina variegata, and Bombina bombina). Mean graft survival times were significantly prolonged at the low temperature in a species-specific manner, the edible frog (R. esculenta) being the most sensitive and the common toad (Bufo bufo) relatively resistant. Allografts were more temperature-dependent than xenografts; in the latter case, temperature sensitivity was specific to each donor-host combination. Rejection of second-set grafts in R. esculenta was accelerated both in warmth and in cold, but second-set grafts were less temperature-sensitive than sensitizing ones. Both in summer and in winter, R. esculenta rejected allografts promptly at 22 degrees C but slowly at 10 degrees C. In both seasons, Bombina variegata kept at 22 degrees C rejected allografts in a chronic manner. This indicates that amphibian transplantation immunity depends on the donor-host genetic disparity and ambient temperature but is independent of season.     

Histological and mechanical comparison of hydroxyapatite-coated cobalt-chrome and titanium implants in the rabbit femur

The purpose of this study was to compare hydroxyapatite (HA)-coated titanium (Ti) and HA-coated cobalt-chrome (CoCr) implants in the distal femur of the rabbit by evaluating bone apposition and interfacial shear strength. Bilateral cylindrical implants with a plasma sprayed 50-microns thick HA coating were press-fit into the metaphyseal cancellous bone of the lateral femoral condyles in a transverse fashion, and the animals were sacrificed at 2, 4, and 8 weeks postimplantation. Mechanical strength of the interface between HA and bone was measured using the pushout method. For histologic analysis, the fractional linear extent of bone apposition was quantitated. No differences were found in the interfacial shear strength between the Ti and CoCr at any time period. The amount of bone apposition increased significantly at each time interval for both substrate metals, but there were no significant differences between the two substrates at any of the time periods studied. The HA-coated CoCr implants performed in a similar manner to the HA-coated Ti implants, both mechanically and histologically, suggesting that HA-coated CoCr implants deserve further study as a viable alternative to Ti for the biological fixation of total joint components in orthopaedic surgery.     

Clinicopathological correlation of technetium bone scan in vascularization of hydroxyapatite implants. A primate model

OBJECTIVES: To report the histopathological and bone scan characteristics of the stages of hydroxyapatite fibrovascular integration and to consider the implications for the timing of peg drilling in a primate model. DESIGN: Three monkeys received hydroxyapatite implants covered only anteriorly with a fascia lata button to which the rectus muscles were sutured. Weekly bone scans were evaluated quantitatively and qualitatively. The orbits were harvested at 2, 4, and 8 weeks and examined histopathologically. RESULTS: Quantitatively, the implant's technetium uptake increased, then reached a plateau by 4 weeks. Peripheral uptake was present on the images and histologically at 2 weeks. When bone scan images suggested complete vascularization by the fourth week, the implant was 99% vascularized histologically. Completion of vascularization was ascertained at 8 weeks, without further discernible changes in the bone scans. CONCLUSIONS: The technetium bone scan is sensitive to the vascularization of the hydroxyapatite implant and discerns when complete vascularization is approached. This primate study models closely the clinical findings we have recently reported. We advocate at least a 4-week interval between the time the bone scan suggests full vascularization and peg drilling.     

Histological evaluation of bone reactions to aluminium oxide dental implants in man: a case report

Alumina implants have been shown to possess high biocompatibility. The authors present the case of an aluminium oxide ceramic implant removed because of fracture of the abutment after a 30-month loading period. It was possible to observe microscopically that the implant was covered by highly mineralized mature compact lamellar bone; no connective tissue or inflammatory cells were present at the interface. Osteocytes were observed very close to the bone-implant interface. These features indicate the good biocompatibility of the implant.     

Reconstruction of residual alveolar cleft defects with one-stage mandibular bone grafts and osseointegrated implants

PURPOSE: This study evaluates a treatment regimen for reconstruction of residual maxillary alveolar cleft defects consisting of mandibular bone grafting and immediate implant installation. PATIENTS AND METHODS: Sixteen cleft patients (five female and 11 male) had residual cleft defects of the alveolar ridge reconstructed with bone grafts from the mandibular symphyseal region. The bone graft was pretapped at the donor site before fixation in the residual ridge with Br?nemark implants. Twenty implants were installed according to this concept. The period of observation ranged from 36 to 69 months, with a mean of 48 months after implant installation. RESULTS: Five patients developed wound dehiscenses that resulted in total or partial bone graft sequestration. Two implants were lost, one due to sequestration and the other due to mobility at the abutment procedure; 18 implants were still well functioning at the end of the observation period. However, all patients showed significant periimplant bone resorption after this one-stage treatment. CONCLUSION: Because of the observed complication rate, the one-stage procedure may not be optimal for reconstructing residual cleft defects.     

Evaluation of the healing process in fractures using early and delayed bone scanning

Fifty-two fracture sites were evaluated by bone scintigraphy after acquiring similar views of the lesions at 4 and 24 h following technetium-99m methylene diphosphonate administration. After calculating 24/4 h radio-uptake ratio (RUR) and using 1.15 as the critical point of separation, fresh healing lesions could be separated from old healed fractures persisting as 'hot spots' with a sensitivity of 100% and specificity of 82%. The 24/4 h RUR technique is a new approach in measuring the osteoblastic activity at the lesion site. The technique appears to have clinical significance in the detection and follow up of the healing status of occult fractures where radiological procedures are of limited value.     

A quantitative comparison of machined commercially pure titanium and titanium-aluminum-vanadium implants in rabbit bone

BACKGROUND: Grass group I consists of very potent allergenic components which are found in the pollen of all temperate grasses. Several post-translational modifications are predicted from the cDNA data. OBJECTIVE: The aim of this study was to identify sequential IgE-binding sites on the allergen Phl p 1 and to determine their influence on IgE reactivity. METHODS: Based on cDNA data and microsequencing results we synthesized overlapping decapeptides covering the complete Phl p 1 molecule and tested them for immunological reactivity by means of the PEPSCAN technique. In a dot test we determined the frequency of IgE reactivities to post-translationally modified structures (hydroxylated proline residues, carbohydrate structure, and disulphide formations). RESULTS: Screening by overlapping peptides demonstrated an IgE binding site on the 10 N-terminal amino acids. Comprehensive studies showed that the two hydroxyproline residues of the native Phl p 1 allergen (at positions 5 and 8) and the N-glycan (at position 9) can result in an increased IgE reactivity; 3.3% of the sera exclusively bound to the hydroxyproline bearing peptide, while only 0.4% bound to the proline containing peptide. With regard to glycosylation, we estimated that 20% of sera recognized protein and carbohydrate epitopes, while one serum exclusively bound to the glycan. The formation of disulphide bonds has no detectable effect on the IgE reactivity to Phl p 1. CONCLUSION: Our results indicate that the post-translational modifications, the carbohydrate structure and the hydroxylation of proline residues, can enhance the IgE reactivity of Phl p 1.     

Laparoscopic versus open posterior adrenalectomy: comparison of acute-phase response and wound healing in the cushingoid porcine model

This prospective randomized study examined the acute-phase response and wound healing, comparing laparoscopic (LA) and open posterior (PA) adrenalectomy in a cushingoid porcine model. Repository corticotropin gel was given to 40 pigs for 21 days. Biochemical and tissue parameters of Cushing syndrome were confirmed. The pigs were randomized to undergo LA or PA. In addition to operating time and morbidity, the acute-phase response was compared by measuring the postoperative white blood cell count, fasting glucose, C-reactive protein, and nitrogen balance. Wound healing was assessed by (1) scored (1-4) gross appearance at 48 hours and 1 and 2 weeks; (2) histologic examination; and (3) tensile strength. There was no difference in operating time (mean +/- SD) (36 +/- 9 minutes open vs. 37 +/- 7 minutes laparoscopic), perioperative mortality, degree of leukocytosis, fasting glucose, or C-reactive protein (p > 0.05). Nitrogen balance, wound scores, and tensile strength at 24 hours and 1 week were more favorable in the LA group than in the PA group (p < 0.05). In the cushingoid porcine model, laparoscopic adrenalectomy was less catabolic and was associated with fewer wound complications than the open posterior adrenalectomy. These findings provide support for continued pursuit of laparoscopic methods for adrenalectomy in the clinical setting.     

Expression of wound healing and stress-related proteins in keratoconus corneas

PURPOSE: Keratoconus is characterized by thinning and scarring of the central portion of the cornea. This study was performed on keratoconus corneas to examine the expression of proteins related to wound healing including vimentin, an intermediate filament protein, and tenascin, and extracellular matrix protein. The expression of stress-related cytokines, heat shock proteins and ubiquitin was also investigated. METHODS: Corneal buttons were collected from patients with keratoconus, normal subjects and patients with other corneal diseases such as pseudophakic bullous keratopathy. Immunofluorescence staining was performed on frozen sections for vimentin and tenascin, and immunoperoxidase staining was carried out on paraffin sections for cytokines, heat shock proteins and ubiquitin. RESULTS: To varying degrees, all proteins examined, except tenascin and heat shock protein 90, were found to be expressed in normal human corneas. The expression of vimentin, tenascin, transforming growth factor-beta, interleukin-1, heat shock protein 27, and ubiquitin was enhanced in keratoconus corneas. A similar enhancement however was also observed in other diseased corneas. CONCLUSIONS: Altered expression of several wound healing or stress-related proteins was noted in keratoconus corneas. The alterations appear to be nonspecific injury or wound responses in association with corneal diseases.     

A comparison of vascularized and nonvascularized bone grafts for reconstruction of mandibular continuity defects

PURPOSE: This study compared vascularized and nonvascularized bone grafts for the reconstruction of segmental defects of the mandible. PATIENTS AND METHODS: The results in 39 patients having vascularized bone grafts (38 fibulas and one iliac crest) and 29 patients having nonvascularized bone grafts (26 iliac crest [22 corticocancellous block grafts, four cancellous bone grafts in a tray] and three rib grafts) for segmental mandibular reconstruction were evaluated in terms of overall success rate, total number of surgeries performed, total blood loss, total number of hospital days, and total number of hours in the operating room. RESULTS: Of 39 vascularized bone grafts, two failed (95% success rate), whereas of 29 nonvascularized bone grafts, seven failed (76% success rate). Failure for the nonvascularized bone grafts was closely correlated to the length of the defect. Nonvascularized bone graft patients underwent an average of one more surgical procedure for total reconstruction than vascularized bone graft patients, including osseointegrated implants. However, vascularized bone graft patients spent a mean of over 14 additional days in the hospital for all of their reconstructive procedures and an additional 3 hours in the operating room as compared with nonvascularized bone graft patients. Blood loss was similar in both groups (1,100 mL). Only 20% to 24% of patients in each treatment group have completed reconstruction to include osseointegrated implants. CONCLUSIONS: The success rate for vascularized bone grafting is high and is the treatment of choice when primary reconstruction is required, when the patient has been previously irradiated, or when simultaneous replacement of soft tissue is required. Vascularized bone grafts are also the treatment of choice for mandibular replacements over 9 cm in length. Nonvascularized bone grafts create a better contour and bone volume for facial esthetics and subsequent implant insertion, and may be the treatment of choice for secondary reconstruction of defects less than 9 cm in length.     

The effects of guided bone regeneration and grafting on implants placed into immediate extraction sockets. An experimental study in dogs

Guided bone regeneration (gbr) for the treatment of insufficient bone volume around implants can be performed using membranes with or without grafting materials (i.e., autogenous, allogenous, xenogenous, or alloplastic grafts). A possible way to evaluate the quality of implant osseointegration is the torque necessary to remove implants from their bony housing. The aim of this study was to compare the torques necessary to remove dental implants from implant beds reconstructed with different bone substitutes and GBR or GBR alone in 6 adult mongrel dogs. All mandibular premolars were extracted and 3 extraction sockets on each side were enlarged using a trephine bur. A 13 mm titanium screw-type dental implant (3.75 mm diameter) was placed in each enlarged extraction socket so that only the apical 3 to 4 mm were engaged in bone. The 3 defects were then randomly treated with either 1) canine demineralized freeze-dried bone allograft (DFDBA) plus GBR using an expanded polytetrafluoroethylene membrane (DFDBA+GTAM); 2) bioabsorbable hydroxyapatite and GBR (HA+GTAM); or 3) GBR (GTAM alone). After 6 months, the torque to remove the implants was measured in 4 animals and analyzed using ANOVA. There were no statistically significant differences between the 3 groups (GTAM alone: 46.37+/-16.41 Ncm; HA+GTAM: 46.00+/-16.59 Ncm; DFDBA+ GTAM: 52.15+/-29.24 Ncm). In addition, the influence of early removal of barriers on the torque values was evaluated with the t-test. Comparing exposed versus retained membranes by treatment modality, the only statistically significant difference was found in the DFDBA+GTAM group. When the torque values of all implants with exposed and retrieved membranes were compared to all those with retained membranes a significant difference could be detected. Histologic sections were prepared from the 2 dogs not included in the removal torque testing. In the histometric analysis the GTAM alone group showed a mean mineralized bone-to-implant-contact of 27.1%, the DFDBA+GTAM group of 34.6%, and the HA+GTAM of 39.3%. The mineralized bone-to-implant-contact of the HA+GTAM group was significantly higher than that of the GTAM alone group. In addition, the mineralized bone-to-implant-contact was divided into an apical and coronal part using the apical seventh thread as the dividing landmark. In the apical region, there was no significant difference between the groups regarding mineralized bone-to-implant-contact. In the coronal part the mineralized bone-to-implant-contact of the GTAM alone group was significantly lower compared to the other 2 groups. Within the limits of this investigation, it can be concluded that the type of grafting material will not influence torque removal values, but that early membrane exposure and removal will negatively influence the torque measurements. The combination of GBR with a bone substitute increased the mineralized bone-to-implant contact.     

Maxillary sinus augmentation using different grafting materials and dental implants in monkeys. Part I. Evaluation of anorganic bovine-derived bone matrix

The aim of this study was to evaluate clinically, histologically and histometrically the use of anorganic bovine bone matrix (i.e. Bio-oss) as a grafting material for maxillary sinus augmentation procedures. In 4 adult male rhesus monkeys (i.e. Macaca mulatta) the 1st, 2nd and 3rd maxillary molars on one side of the jaws were extracted. The remaining bone between the alveolar crest and the bottom of the sinus was then reduced to 3-4 mm. After 3 months, maxillary sinus augmentation procedures were performed on one side of the jaws in each monkey and the sinuses were grafted with the bovine bone matrix. At that time, 2 IMZ pure titanium plasma coated implants were immediately placed into the augmented sinuses (i.e. simultaneous implants-loaded group). After 4 months, 2 additional similar implants were placed into these previously augmented sinuses (i.e. delayed implants-loaded group). Four months later, the abutment connection was performed and all 4 implants were loaded with a gold-alloy bridge for 6 months (i.e. until sacrifice of the animals). The contralateral side of each monkey received the same treatment with the exception that the extractions were performed 7 months after those in the opposite side and that the implants in this side were not loaded. Thus, 2 additional study groups (i.e. simultaneous implants-unloaded group and delayed implants-unloaded group) were obtained. Clinically, all loaded implants were stable at the day of sacrifice. Histologically, the grafted sinuses exhibited significant bone formation with integration of the bovine bone matrix particles to the new bone. Direct mineralized bone-to-implant contact was greater for the delayed implant placement groups than for the implants installed simultaneously with the sinus augmentation. Furthermore, the percentage of direct mineralized bone-to-implant contact was greater in the residual bone than in the augmented area. It was concluded that the anorganic bovine bone matrix facilitated bone formation and implant osseointegration in the augmented sinuses and that the delayed implant placement in combination with the sinus augmentation procedure seemed to be preferable.     

Comparison of demineralized allogeneic bone matrix grafting (the Urist procedure) and the Ilizarov procedure in large diaphyseal defects in sheep

The bone inductive capability of the Urist and Ilizarov procedures was compared in the repair of large diaphyseal defects in sheep. In 30 animals, a 4 cm segmental defect was created in the middle portion of the right femur and was stabilized with an external fixator. The sheep were divided into four groups according to the type of reconstruction of the defect. In group 1, a demineralized allogeneic bone matrix (DABM) cylinder was used; in group 2, DABM chips; and in group 3, gradual transport of a piece of bone detached from the proximal femoral fragment was used to fill the defect. Group 4 served as a control (the defect was left empty). New bone formation was assessed by serial radiographs until the time of death at 2 or 4 months. Postmortem specimens were analyzed with respect to bone mineral content, uptake of isotopes (45Ca and 3H-proline), and histology. The first signs of new bone formation were radiographically evident at 4 weeks. In the two groups in which reconstruction involved DABM (Urist procedures), new bone failed to form in eight of the 13 animals. Full bridging of the defect was observed at 8 weeks in one animal with a DABM cylinder and two with DABM chips. No decisive difference in bone yield could be demonstrated between the two Urist procedures. In the group treated with the Ilizarov procedure, new bone formation consistently occurred at a high rate; full bridging of the defect was observed in seven of the eight animals. Bone mineral scanning and histologic analysis essentially confirmed the radiographic results. Uptake of isotopes was selectively analyzed in two sheep from each experimental group in which new bone formation was exhibited in the defect; new bone formation was increased compared with that in the contralateral femur but was equal among the three experimental groups. Our study shows that gradual transport of a detached piece of autogeneic bone (Ilizarov procedure) is more effective than implantation of DABM (Urist procedure) in eliciting new bone formation in large diaphyseal defects in sheep. The variable bone induction by DABM may be explained by differences in host immune responses to the implants.     

Role of serum nonsuppressible insulin-like activity (NSILA) in wound healing. I. Influence of thyroparathyroidectomy on serum NSILA and wound healing in the rat

Serum contains a 90,000 molecular weight glycoprotein that exhibits insulin-like activity on adipocytes, skeletal muscle, and fibroblasts in tissue culture; however, this protein is physicochemically and immunochemically distinct from insulin and presently is termed "nonsuppressible insulin-like activity ("nsilA)." This study was designed to assess the response of serum NSILA to thyroparathyroidectomy (TPTHX) and to associate this response with tissue repair processes in the injured rat. It was postulated that NSILA modulates the fibroblastic response in wound healing. TPTHX decreased NSILA to 40 percent of control levels (p less than 0.001); 90 male animals subsequently were wounded by either a 10 percent third-degree burn or skin excision. Following injury, NSILA significantly increased in both control and TPTHX groups, but this acute-phase response was attenuated in TPTHX animals. Light microscopy of granulation tissue demonstrated a diminution in the fibroblastic response in TPTHX animals. Hydroxyproline analysis of granulation tissue revealed a significant decrease (p less than 0.025) in collagen content in TPTHX animals with low NSILA levels. The results suggest that serum NSILA levels are controlled, in part, by thyroid hormone and that NSILA may modulate the fibroblastic response of connective tissue repair processes.     

TGF-beta1 influences early gingival wound healing in rats: an immunohistochemical evaluation of stromal remodelling by extracellular matrix molecules and PCNA

The effect of topically applied transforming growth factor beta1 (TGF-beta1) on the rat gingival wound healing process after flap surgery was evaluated by immunohistochemistry for extracellular matrix molecules (ECM), such as tenascin, heparan sulfate proteoglycan (HSPG) and type IV collagen, and for proliferating cell nuclear antigen (PCNA) in fibroblasts. TGF-beta1 solution was applied to the surgical wound experimental sites. Two microg/microl were applied at the time of the operation, and 1 microg/microl at days 1 and 2 after surgery, with contralateral control sites receiving the vehicle alone. Periodontal tissues were histologically examined at 3 and 7 days post-surgery. Tenascin was found to be more strongly stained in the granulation tissue from experimental sites at 3 days post-surgery. At 7 days postsurgery, HSPG-positive areas in granulation tissue had become smaller and there was a prominent proliferation of PCNA-positive fibroblast-like cells and type IV collagen-positive blood vessels. These results suggest that TGF-beta1 applied to surgical wounds influences early proliferation of gingival fibroblast-like cells, the formation of blood vessels, and ECM remodelling. In conclusion, TGF-beta1 application appears to promote granulation tissue formation in periodontal wound healing.     

A comparison of bone scintigraphy and MRI in the early diagnosis of the occult scaphoid waist fracture

OBJECTIVE: To determine the accuracy of MRI in the assessment of the radiographically occult scaphoid fracture. DESIGN: This prospective study compared the sensitivity and specificity of MRI for detection of radiographically occult scaphoid fractures with bone scintigraphy (BS), the currently accepted imaging modality of choice. Consecutive patients with clinical signs of a scaphoid injury but no evidence of fracture on plain radiographs at presentation and after 7-10 days were evaluated by MRI and BS. All images were reported in masked fashion and the sensitivities and specificities of the imaging modalities determined. All patients with a scaphoid fracture demonstrated by MRI or BS were followed for at least a year after injury. PATIENTS: Forty-three subjects (aged 12-74 years) had both MRI and BS carried out on average 19 days from the injury date. RESULTS AND CONCLUSIONS: Six patients (14%) had scaphoid waist fractures. There were other bony injuries in a further six. In 40 patients there was agreement between the BS and MRI findings. In three cases there was discrepancy between the imaging modalities; in all three MRI was found to be the more sensitive and specific. MRI could become the investigation of choice for this injury.