Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model

Mesenchymal stem cells (MSCs) provide an important source of pluripotent cells for musculoskeletal tissue repair. This study examined the impact of MSC implantation on cartilage healing characteristics in a large animal model. Twelve full-thickness 15-mm cartilage lesions in the femoropatellar articulations of six young mature horses were repaired by injection of a self-polymerizing autogenous fibrin vehicle containing mesenchymal stem cells, or autogenous fibrin alone in control joints. Arthroscopic second look and defect biopsy was obtained at 30 days, and all animals were euthanized 8 months after repair. Cartilage repair tissue and surrounding cartilage were assessed by histology, histochemistry, collagen type I and type II immunohistochemistry, collagen type II in situ hybridization, and matrix biochemical assays. Arthroscopic scores for MSC-implanted defects were significantly improved at the 30-day arthroscopic assessment. Biopsy showed MSC-implanted defects contained increased fibrous tissue with several defects containing predominantly type II collagen. Long-term assessment revealed repair tissue filled grafted and control lesions at 8 months, with no significant difference between stem cell-treated and control defects. Collagen type II and proteoglycan content in MSC-implanted and control defects were similar. Mesenchymal stem cell grafts improved the early healing response, but did not significantly enhance the long-term histologic appearance or biochemical composition of full-thickness cartilage lesions.

Evaluation of a novel biphasic calcium phosphate in standardized bone defects: a histologic and histomorphometric study in the mandibles of minipigs

OBJECTIVE: A novel biphasic calcium phosphate (CaP) granulate consisting of hydroxyapatite (HA) and beta-tricalciumphosphate (TCP) was compared with pure HA and pure TCP and with autograft as positive control. MATERIALS AND METHODS: Four standardized bone defects were prepared in both mandibular angles of 16 minipigs and grafted with autogenous bone chips, HA, HA/TCP (60% : 40%), or TCP. Histologic and histomorphometric analysis of bone formation and graft degradation followed healing periods of 2, 4, 8, and 24 weeks. RESULTS: 2 weeks: more bone formation in defects filled with autograft than with the three CaP materials (P<0.05). 4 weeks: bone formation differed significantly (P<0.05) between all four materials (autograft>TCP>HA/TCP>HA). 8 weeks: more bone formation in defects with autograft and TCP than with HA/TCP (P<0.05), and HA/TCP had more bone formation than HA (P<0.05). 24 weeks: no difference in bone formation between the groups. Autograft and TCP resorbed quickly and almost completely over 8 weeks, whereas HA/TCP and HA showed limited degradation over 24 weeks. CONCLUSION: All defects healed with mature lamellar bone and intimate contact between bone and the remaining graft material. The rate of bone formation corresponded to the content of TCP in the CaP materials.

Reconstruction of Skull Base and Fronto-orbital Defects following Tumor Resection

Reconstruction of the anterior skull base and fronto-orbital framework following extensive tumor resection is both challenging and controversial. Dural defects are covered with multiple sheets of fascia lata that provide sufficient support and avoid herniation. Plating along the skull base is contraindicated. After resection of orbital walls, grafting is necessary if the periosteum or parts of the periorbital tissue had to be removed, to avoid enophthalmus or strabism. Free bone grafts exposed to the sinonasal or pharyngeal cavity are vulnerable to infection or necrosis: therefore, covering the grafts with vascularized tissue, such as the Bichat fat-pad or pedicled temporalis flaps, should reduce these complications. Alloplastic materials are indispensable in cranial defects, whereas microsurgical free tissue transfer is indicated in cases of orbital exenteration and skin defects. The authors review their experience and follow-up of 122 skull base reconstructions following extensive subcranial tumor resection. Most significant complications were pneumocranium in 4.9%, CSF leaks in 3.2%, and partial bone resorption in 8.1%.

Oral implants placed in bone defects treated with Bio-Oss, Ostim-Paste or PerioGlas: an experimental study in the rabbit tibiae

OBJECTIVES: To compare the histological features of bone filled with Bio-Oss, Ostim-Paste or PerioGlas placed in defects in the rabbit tibiae by evaluating bone tissue composition and the integration of titanium implants placed in the grafted bone. MATERIAL AND METHODS: Two cylindrical bone defects, about 4 mm in diameter and 6 mm in depth, were created in the tibiae of 10 rabbits. The defects were filled with either Bio-Oss, PerioGlas, Ostim-Paste or left untreated, and covered with a collagen membrane. Six weeks later, one titanium sandblasted and acid-etched (SLA) implant was inserted at the centre of each previously created defect. The animals were sacrificed after 6 weeks of healing. RESULTS: Implants placed in bone previously grafted with Bio-Oss, PerioGlas or Ostim-Paste obtained a larger extent of osseointegration, although not statistically significant, than implants placed in non-grafted bone. The three grafting materials seemed to perform in a similar way concerning their contribution towards implant osseointegration. All grafting materials appeared to be osteoconductive, thus leading to the formation of bridges of mineralized bone extending from the cortical plate towards the implants surface through the graft scaffold. CONCLUSIONS: Grafting with the above-mentioned biomaterials did not add any advantage to the osseointegration of titanium SLA implants in a self-contained defect.

Comparative study of biphasic calcium phosphates with different HA/TCP ratios in mandibular bone defects. A long-term histomorphometric study in minipigs

Three biphasic calcium phosphate (BCP) bone substitute materials with hydroxyapatite (HA)/tricalcium phosphate (TCP) ratios of 20/80, 60/40, and 80/20 were compared to coagulum, particulated autogenous bone, and deproteinized bovine bone mineral (DBBM) in membrane-protected bone defects. The defects were prepared in the mandibles of 24 minipigs that were divided into four groups of six with healing times of 4, 13, 26, and 52 weeks, respectively. The histologic and histomorphometric evaluation focused on differences in amount and pattern of bone formation, filler degradation, and the interface between bone and filler. Collapse of the expanded polytetrafluoroethylene barrier membrane into the coagulum defects underlined the necessity of a filler material to maintain the augmented volume. Quantitatively, BCP 20/80 showed bone formation and degradation of the filler material similar to autografts, whereas BCP 60/40 and BCP 80/20 rather equaled DBBM. Among the three BCP's, the amount of bone formation and degradation of filler material seemed to be inversely proportional to the HA/TCP ratio. The fraction of filler surface covered with bone was highest for autografts at all time points and was higher for DBBM than BCP 80/20 and 60/40 at the early healing phase. TRAP-positive multinucleated cells were identified on BCP and DBBM surfaces without showing typical signs of resorption lacunae.

Adrenal gland development and defects

The network regulating human adrenal development is complex. Studies of patients with adrenal insufficiency due to gene mutations established a central role for transcription factors GLI3, SF1 and DAX1 in the initial steps of adrenal formation. Adrenal differentiation seems to depend on adrenocorticotropic hormone (ACTH) stimulation and signalling, including biosynthesis and action of POMC, PC1, TPIT, MC2R, MRAP and ALADIN, all of which cause adrenocortical hypoplasia when mutated in humans. Studies of knockout mice revealed many more factors involved in adrenal development; however, in contrast to rodents, in humans several of those factors had no adrenal phenotype when mutated (e.g. WT1, WNT4) or, alternatively, human mutations have not (yet) been identified. Tissue profiling of fetal and adult adrenals suggested 69 genes involved in adrenal development. Among them were genes coding for steroidogenic enzymes, transcription and growth factors, signalling molecules, regulators of cell cycle and angiogenesis, and extracellular matrix proteins; however, the exact role of most of them remains to be elucidated.

Composite skin grafts for basal cell carcinoma defects of the nose

Basal cell carcinoma is the most frequent cutaneous cancer of the nose and is characterized by its local spreading and exceptionally rare tendency to metastasize. Since a significant advantage has been seen in surgery compared to other treatments, surgical excision ensuring the highest chance of cure is frequently employed. Excision defects of the nose may be covered with either local flap or a full-thickness skin graft. In resurfacing such defects following excision of basal cell carcinomas, we favor the technique of composite-skin grafting which involves the harvesting of composite-skin graft including the epidermis, dermis and superficial layers of subcutaneous tissue to obtain the required thickness in the recipient site. This technique was used for defects remaining after the excision of basal cell carcinomas in a series of 15 patients. The areas involved were lateral nasal region (5 cases), nasal tip (4 cases), dorsum (3 cases), alar lobule (2 cases), and soft triangle (1 case). The mean follow-up was 14.2 months. The color, texture and thickness of the composite-skin graft harvested from the preauricular site and the neck compare favorably with the skin of the nose region. Satisfactory results, both clinically and in patient appreciation, have been obtained in both the reconstruction site and the appearance of the donor site in all patients.

A new method to monitor visual field defects caused by photoreceptor degeneration by quantitative optical coherence tomography

PURPOSE: To correlate the dimension of the visual field (VF) tested by Goldman kinetic perimetry with the extent of visibility of the highly reflective layer between inner and outer segments of photoreceptors (IOS) seen in optical coherence tomography (OCT) images in patients with retinitis pigmentosa (RP). METHODS: In a retrospectively designed cross-sectional study, 18 eyes of 18 patients with RP were examined with OCT and Goldmann perimetry using test target I4e and compared with 18 eyes of 18 control subjects. A-scans of raw scan data of Stratus OCT images (Carl Zeiss Meditec, AG, Oberkochen, Germany) were quantitatively analyzed for the presence of the signal generated by the highly reflective layer between the IOS in OCT images. Starting in the fovea, the distance to which this signal was detectable was measured. Visual fields were analyzed by measuring the distance from the center point to isopter I4e. OCT and visual field data were analyzed in a clockwise fashion every 30 degrees , and corresponding measures were correlated. RESULTS: In corresponding alignments, the distance from the center point to isopter I4e and the distance to which the highly reflective signal from the IOS can be detected correlate significantly (r = 0.75, P < 0.0001). The greater the distance in VF, the greater the distance measured in OCT. CONCLUSIONS: The authors hypothesize that the retinal structure from which the highly reflective layer between the IOS emanates is of critical importance for visual and photoreceptor function. Further research is warranted to determine whether this may be useful as an objective marker of progression of retinal degeneration in patients with RP.

Comparison between confocal scanning laser tomography, scanning laser polarimetry and optical coherence tomography on the ability to detect localised retinal nerve fibre layer defects in glaucoma patients

BACKGROUND/AIM: To compare the ability of confocal scanning laser tomography (CSLT), scanning laser polarimetry (SLP) and optical coherence tomography (OCT) in recognising localised retinal nerve fibre layer (RNFL) defects. METHODS: 51 eyes from 43 patients with glaucoma were identified by two observers as having RNFL defects visible on optic disc photographs. 51 eyes of 32 normal subjects were used as controls. Three masked observers evaluated CSLT, SLP and OCT images to determine subjectively the presence of localised RNFL defects. RESULTS: Interobserver agreement was highest with OCT, followed by SLP and CSLT (mean kappa: 0.83, 0.69 and 0.64, respectively). RNFL defects were identified in 58.8% of CSLT, 66.7% of SLP and 54.9% of OCT (p = 0.02 between SLP and OCT) by at least two observers. In the controls, 94.1% of CSLT, 84.3% of SLP and 94.1% of OCT scans, respectively, were rated as normal (p = 0.02 between CSLT and SLP, and SLP and OCT). CONCLUSION: Approximately 20-40% of localised RNFL defects identified by colour optic disc photographs are not detected by CSLT, SPL or OCT. SLP showed a higher number of false-positive results than the other techniques, but also had a higher proportion of correctly identified RNFL defects in the glaucoma population.

Prenatal diagnosis and treatment planning of congenital heart defects-possibilities and limits

BACKGROUND: Newborns with hypoplastic left heart syndrome (HLHS) or right heart syndrome or other malformations with a single ventricle physiology and associated hypoplasia of the great arteries continue to be a challenge in terms of survival. The vast majority of these forms of congenital heart defects relate to abnormal morphogenesis during early intrauterine development and can be diagnosed accurately by fetal echocardiography. Early knowledge of these conditions not only permits a better understanding of the progression of these malformations but encourages some researchers to explore new minimally invasive therapeutic options with a view to early pre- and postnatal cardiac palliation. DATA SOURCES: PubMed database was searched with terms of "congenital heart defects", "fetal echocardiography" and "neonatal cardiac surgery". RESULTS: At present, early prenatal detection has been applied for monitoring pregnancy to avoid intrauterine cardiac decompensation. In principle, the majority of congenital heart defects can be diagnosed by prenatal echocardiography and the detection rate is 85%-95% at tertiary perinatal centers. The majority, particularly of complex congenital lesions, show a steadily progressive course including subsequent secondary phenomena such as arrhythmias or myocardial insufficiency. So prenatal treatment of an abnormal fetus is an area of perinatal medicine that is undergoing a very dynamic development. Early postnatal treatment is established for some time, and prenatal intervention or palliation is at its best experimental stage in individual cases. CONCLUSION: The upcoming expansion of fetal cardiac intervention to ameliorate critically progressive fetal lesions intensifies the need to address issues about the adequacy of technological assessment and patient selection as well as the morbidity of those who undergo these procedures.

Effect of two bioabsorbable barrier membranes on bone regeneration of standardized defects in calvarial bone: a comparative histomorphometric study in pigs

BACKGROUND: The effect of two different bioabsorbable collagen membranes on bone regeneration was assessed in standardized, membrane-protected calvarial defects in pigs. METHODS: Two standardized defect types (6 x 6 x 6 mm and 9 x 9 x 9 mm) were produced in the calvaria of pigs: empty defects without a membrane (group 1; eight defects per size); defects filled with deproteinized bovine bone mineral (DBBM) without a membrane (group 2; eight defects per size); defects filled with DBBM and covered by a collagen membrane (group 3; eight defects per size); and defects filled with DBBM and covered by a cross-linked collagen membrane (CCM) (group 4; eight defects per size). Sacrifice took place 16 weeks after surgery, and the following parameters were analyzed: descriptive histology; semiquantitative histology (SQH), assessing bone regeneration in the whole defect area; and histomorphometric analysis of the percentage of bone and DBBM in the regenerated area at three different depth levels of the defect. RESULTS: Using SQH, both membrane types resulted in significantly better bone regeneration compared to groups 1 and 2, irrespective of the defect size (P <0.005), with no difference between the two membranes. In the histomorphometric analysis, the layer immediately below the surface exhibited a significantly higher percentage of bone in groups 3 (27%) and 4 (36%) versus the two other groups for the 9 x 9 x 9-mm defects. No such differences were apparent for the 6 x 6 x 6-mm defects or the other two depth levels (bottom and middle layer) for either defect size. CONCLUSIONS: The two collagen membranes tested significantly enhanced bone regeneration, especially in the superficial level of the calvarial bone defects. The prototype CCM did not provide any further advantage in the present animal model.

Failures and complications in patients with birth defects restored with fixed dental prostheses and single crowns on teeth and/or implants

OBJECTIVES: To assess retrospectively, over at least 5 years, the incidences of technical and biological complications and failures in young adult patients with birth defects affecting the formation of teeth. MATERIAL AND METHODS: All insurance cases with a birth defect that had crowns and fixed dental prostheses (FDPs) inserted more than 5 years ago were contacted and asked to participate in a reexamination. RESULTS: The median age of the patients was 19.3 years (range 16.6-24.7 years) when prosthetic treatment was initiated. Over the median observation period of 15.7 years (range 7.4-24.9 years) and considering the treatment needs at the reexamination, 19 out of 33 patients (58%) with reconstructions on teeth remained free from all failures or complications. From the patients with FDPs and single unit crowns (SCs) on implants followed over a median observation period of 8 years (range 4.6-15.3 years), eight out of 17% or 47% needed a retreatment or repair at some point due to a failure or a complication. From the three groups of patients, the cases with amelogenesis/dentinogenesis imperfecta demonstrated the highest failure and complication rates. In the cases with cleft lip, alveolus and palate (CLAP) or hypodontia/oligodontia, 71% of the SCs and 73% of the FDPs on teeth (FDP T) remained complication free over a median observation period of about 16 years. Sixty-two percent of the SCs and 64% of the FDPs on implants remained complication free over 8 years. Complications occurred earlier with implant-supported reconstructions. CONCLUSIONS: Because healthy, pristine teeth can be left unprepared, implant-supported SCs and FDPs are the treatment choice in young adults with birth defects resulting in tooth agenesis and in whom the edentulous spaces cannot be closed by means of orthodontic therapy. However, the trend for earlier and more frequent complications with implant-supported reconstructions in young adults, expecting many years of function with the reconstructions, has to be weighed against the benefits of keeping teeth unprepared. In cases with CLAP in which anatomical conditions render implant placement difficult and in which teeth adjacent to the cleft require esthetic corrections, the conventional FDP T still remains the treatment of choice.

Cumulative costs for the prosthetic reconstructions and maintenance in young adult patients with birth defects affecting the formation of teeth

OBJECTIVES: To assess retrospectively the cumulative costs for the long-term oral rehabilitation of patients with birth defects affecting the development of teeth. METHODS: Patients with birth defects who had received fixed reconstructions on teeth and/or implants > or =5 years ago were asked to participate in a comprehensive clinical, radiographic and economic evaluation. RESULTS: From the 45 patients included, 18 were cases with a cleft lip and palate, five had amelogenesis/dentinogenesis imperfecta and 22 were cases with hypodontia/oligodontia. The initial costs for the first oral rehabilitation (before the age of 20) had been covered by the Swiss Insurance for Disability. The costs for the initial rehabilitation of the 45 cases amounted to 407,584 CHF (39% for laboratory fees). Linear regression analyses for the initial treatment costs per replaced tooth revealed the formula 731 CHF+(811 CHF x units) on teeth and 3369 CHF+(1183 CHF x units) for reconstructions on implants (P<.001). Fifty-eight percent of the patients with tooth-supported reconstructions remained free from failures/complications (median observation 15.7 years). Forty-seven percent of the patients with implant-supported reconstructions remained free from failures/complications (median observation 8 years). The long-term cumulative treatment costs for implant cases, however, were not statistically significantly different compared with cases reconstructed with tooth-supported fixed reconstructions. Twenty-seven percent of the initial treatment costs were needed to cover supportive periodontal therapy as well as the treatment of technical/biological complications and failures. CONCLUSION: Insurance companies should accept to cover implant-supported reconstructions because there is no need to prepare healthy teeth, fewer tooth units need to be replaced and the cumulative long-term costs seem to be similar compared with cases restored on teeth.

Effect of platelet-rich plasma on the healing of intrabony defects treated with an anorganic bovine bone mineral: a pilot study

BACKGROUND: Periodontal therapy using the combination of platelet-rich plasma (PRP) and different grafting materials has been suggested as a modality to enhance the outcome of regenerative surgery. In most clinical studies, a barrier membrane was used to cover the defects, and thus, the effects of PRP may have been masked by the effects of the barrier. The data from controlled clinical studies evaluating the effect of regenerative therapy using various grafting materials with or without PRP are still limited. The purpose of this study was to clinically compare the healing of intrabony defects treated with either a combination of an anorganic bovine bone mineral (ABBM) and PRP to those obtained with ABBM alone. METHODS: Thirty patients with advanced chronic periodontal disease and displaying one intrabony defect were randomly treated with PRP + ABBM or ABBM alone. The following clinical parameters were evaluated at baseline and 1 year after treatment: plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), gingival recession (GR), and clinical attachment level (CAL). The primary outcome variable was CAL. RESULTS: No statistical significant differences in any of the investigated parameters between the two groups were observed at baseline. Healing was uneventful in all patients. In the PRP + ABBM group, mean PD decreased from 8.6 +/- 1.8 mm to 3.4 +/- 1.4 mm (P <0.001) and mean CAL changed from 9.9 +/- 1.7 mm to 5.3 +/- 1.8 mm (P <0.001). In the ABBM group, mean PD decreased from 8.5 +/- 2.0 mm to 3.2 +/- 1.3 mm (P <0.001) and mean CAL changed from 9.6 +/- 1.9 mm to 4.9 +/- 1.5 mm (P <0.001). CAL gains >or=3 mm were measured in 80% (12 of 15 defects) of cases treated with PRP + ABBM and in 87% (13 of 15 defects) of cases treated with ABBM alone. No statistically significant differences in any of the investigated parameters were observed between the two groups at the 1-year reevaluation. CONCLUSIONS: Within the limits of the present study, it can be concluded that 1) at 1 year after regenerative surgery with PRP + ABBM and ABBM alone, significant PD reductions and CAL gains were found, and 2) the use of PRP failed to improve the results obtained with ABBM alone.