Improved tendon healing using bFGF, BMP-12 and TGFß1 in a rat model.

Several growth factors (GFs) are expressed as tendons heal, but it remains unknown whether their combined application enhances the healing process. This matter was addressed by applying a combination of basic fibroblast growth factor (bFGF), bone morphogenetic protein 12 (BMP-12) and transforming growth factor beta 1 (TGFß1) in a rat Achilles tendon transection model. GFs were applied in one of the three following ways: i) direct application of all three factors at the time of surgery; ii) sequential, tiered percutaneous injection of individual factors immediately after surgery, 48 h and 96 h later; iii) load of all three factors onto a collagen sponge implanted at the time of surgery. After 1, 2, 4 and 8 weeks, healing was assessed based on tendon length and thickness, mechanical strength, stiffness and histology. Best results were achieved when GFs were loaded onto a collagen sponge - with a rapid increase in mechanical strength (load to failure, 71.2 N vs. 7.7 N in controls), consistent tendon length over time (9.9 mm vs. 16.2 mm in controls) and faster tendon remodelling, as measured by histology - followed by tiered injection therapy over 96 h. In conclusion, implantation of a GF-loaded collagen sponge could provide a promising treatment, especially in high-performance athletes and revision cases prone to re-rupture. For conservative treatment, tiered percutaneous GF application could be an option for improving clinical outcome.

Prediction of surface area size in orbital floor and medial orbital wall fractures based on topographical subregions.

OBJECTIVE: This retrospective study evaluates the occurrence and frequency of different fracture patterns in a series of computed tomography (CT) scans in terms of the AOCMF Trauma Classification (TC) orbit module and correlates the assigned defects with measurements of the fracture area in order to get an approximate guideline for fracture size predictions on the basis of the classification. MATERIAL AND METHODS: CT scans of patients with orbital floor fractures were evaluated using the AOCMFTC to determine the topographical subregions. The coding consisted of: W = orbital wall, 1 = anterior orbit, 2 = midorbit, i = inferior, m = medial. The 3-dimensional surface area size of the fractures was quantified by the "defect body" method (Brainlab, Munich, Germany). The fracture area size and its confidence and prediction interval within each topographical subregion was estimated by regression analysis. RESULTS: A total of 137 CT scans exhibited 145 orbital floor fractures, which were combined with 34 medial orbital wall fractures in 31 patients. The floor fractures - W1(i)2(i) (n = 86) and W1(i) (n = 19) were the most frequent patterns. Combined floor and medial wall fractures most frequently corresponded to the pattern W1 (im)2 (im) (n = 15) ahead of W1 (im) 2(i) (n = 10). The surface area size ranged from 0.11 cm2 to 6.09 cm2 for orbital floor and from 0.29 cm2 to 5.43 cm2 for medial wall fractures. The prediction values of the mean fracture area size within the subregions were computed as follows: W1(i) = 2.25 cm2, W2(i) = 1.64 cm2, W1(i)2(i) = 3.10 cm2, W1(m) = 1.36 cm2, W2(m) = 1.65 cm2, W1(m)2(m) = 2.98 cm2, W1 (im) = 3.35 cm2, W1 (im) 2(i) = 4.63 cm2, W1 (im)2(m) = 4.06 cm2 and W1 (im)2 (im) = 7.16 cm2. CONCLUSION: The AOCMFTC orbital module offers a suitable framework for topographical allocation of fracture patterns inside the infero-medial orbital cavity. The involvement of the subregions is of predictive value providing estimations of the mean 3-D fracture area size.

Towards an intraoperative engineering of osteogenic and vasculogenic grafts from the stromal vascular fraction of human adipose tissue.

Grafts generated by cultivation of progenitor cells from the stromal vascular fraction of human adipose tissue have been proven to have osteogenic and vasculogenic properties in vivo. However, in vitro manufacture of such implants is challenged by complex, impractical and expensive processes, and requires implantation in a separate surgery. This study investigates the feasibility of an intraoperative approach to engineer cell-based bone grafts with tissue harvest, cell isolation, cell seeding onto a scaffold and subsequent implantation within a few hours. Freshly isolated adipose tissue cells from a total of 11 donors, containing variable fractions of mesenchymal and endothelial progenitors, were embedded at different densities in a fibrin hydrogel, which was wrapped around bone substitute materials based on beta-tricalcium phosphate (ChronOS), hydroxyapatite (Engipore), or acellular xenograft (Bio-Oss). The resulting constructs, generated within 3 hours from biopsy harvest, were immediately implanted ectopically in nude mice and analysed after eight weeks. All explants contained blood vessels formed by human endothelial cells, functionally connected to the recipient's vasculature. Human origin cells were also found within osteoid structures, positively immunostained for bone sialoprotein and osteocalcin. However, even with the highest loaded cell densities, no frank bone tissue was detected, independently of the material used. These results provide a proof-of-principle that an intraoperative engineering of autologous cell-based vasculogenic bone substitutes is feasible, but highlight that - in the absence of in vitro commitment--additional cues (e.g., low dose of osteogenic factors or orthotopic environmental conditions) are likely needed to support complete osteoblastic cell differentiation and bone tissue generation.

Reconstruction of orbital wall defects: critical review of 72 patients.

Between January 1996 and December 2001, 72 out of 354 patients were included in a retrospective study analysing the outcome of repaired orbital wall defects. Selection was dependent on the availability of pre and postoperative CT scans and on ophthalmologic examination. In particular, orthoptical assessment was performed up to 1 year after operation. In 72 patients, 83 orbital wall defects were analysed and allocated to one of five categories. Accuracy and type of reconstruction were assessed in unilateral orbital wall defects (n=61) and compared with functional outcome. Reconstruction was performed by using PDS membrane (39%), calvarian bone (13%), titanium mesh (7%) or a combination of these materials (37%). Postoperatively, 91% of the patients had normal vision without double images within 20 degrees at every gaze. Accuracy of reconstruction correlated with severity of orbital injury and functional outcome. Functional outcome between category II and III fractures showed no significant difference. The medial margin of the lateral infraorbital fissure being preserved (category II fracture) facilitates reconstruction technically. Accuracy of orbital reconstruction is one important factor to obtain best functional outcome, but other determinants like displacement and/or atrophy of intramuscular cone fat should be considered.

Non-surgical treatment of mandibular fractures--survey of 28 patients.

Between January 1996 and January 2001 28 patients (nine females, nineteen males) with 35 fractures were treated by observation and soft diet only. Patients with isolated high condylar neck fractures were not included. The mean age at time of trauma was 35.6 years (5/80). Only patients with normal occlusion and radiologically undisplaced fractures were included. The follow-up time was 15 weeks on average (8/33). The patients did not undergo any active treatment. They just received the instruction to reduce mouth opening and to take a soft diet for 4 weeks. During the first 2 weeks after the trauma the patients were seen twice a week. Follow-up X-rays were performed after 4 and after 8 to 12 weeks. As a preemptive therapy antibiotics (amoxicillin plus clavulanic acid 2 x 1g/day) were given for 5 days. Spontaneous healing of all fractures was observed. In two patients a tooth had to be removed out of the fracture line. One patient complained about an occlusal problem after 1 week. In his case intermaxillary fixation was installed for 2 weeks. For forensic reasons the patients have to be fully informed about possible complications before indicating this type of management. Patient selection is crucial and requires a highly experienced surgeon. Patient inconvenience due to frequent consultations must be taken into consideration. This type of treatment can be recommended only in selected cases.

Intracranial application of free fasciocutaneous flaps in a novel sandwich technique for skull base reconstruction.

Free tissue transfer has been the gold standard of extensive skull base reconstruction, but the onlay of free flaps onto skull base defects carries the risk of cerebrospinal fluid (CSF) leakage. The purpose of this study was the evaluation of a novel technique of a combined sub- and onlay concept with a partially intracranially positioned folded free fasciocutaneous flap in terms of flap applicability, versatility and complication rate. Within 5 years, 7 patients with anterior (n=4), middle (n=2) or posterior (n=1) skull base defects were reconstructed with free extended lateral arm (n=3) or anterolateral thigh (n=4) flaps. The flaps were partially intracranially positioned and fixed with osteo-dermal sutures. Both flaps proved to be applicable in terms of sealing efficiency, minimizing intracranial flap volume and folding. No flap loss was observed. Specific complications consisted of one pneumocranium via an accessory frontal sinus and one cerebellar herniation due to lumbar CSF loss. No flap failure or haematoma of the intracranial flap part occurred. This new concept of intracranial positioning of fasciocutaneous flaps in a sandwich technique using osteo-dermal sutures should be considered as a primary treatment for skull base reconstruction rather than merely as a salvage manoeuvre.

Engineering of osteoinductive grafts by isolation and expansion of ovine bone marrow stromal cells directly on 3D ceramic scaffolds.

In this work, we investigated whether osteoinductive constructs can be generated by isolation and expansion of sheep bone marrow stromal cells (BMSC) directly within three-dimensional (3D) ceramic scaffolds, bypassing the typical phase of monolayer (2D) expansion prior to scaffold loading. Nucleated cells from sheep bone marrow aspirate were seeded into 3D ceramic scaffolds either by static loading or under perfusion flow and maintained in culture for up to 14 days. The resulting constructs were exposed to enzymatic treatment to assess the number and lineage of extracted cells, or implanted subcutaneously in nude mice to test their capacity to induce bone formation. As a control, BMSC expanded in monolayer for 14 days were also seeded into the scaffolds and implanted. BMSC could be isolated and expanded directly in the 3D ceramic scaffolds, although they proliferated slower than in 2D. Upon ectopic implantation, the resulting constructs formed a higher amount of bone tissue than constructs loaded with the same number of 2D-expanded cells. Constructs cultivated for 14 days generated significantly more bone tissue than those cultured for 3 days. No differences in bone formation were found between samples seeded by static loading or under perfusion. In conclusion, the culture of bone marrow nucleated cells directly on 3D ceramic scaffolds represents a promising approach to expand BMSC and streamline the engineering of osteoinductive grafts.

[Long-term follow-up of 37 patients with retrofixation of the temporomandibular joint disk 1987-1995]. / Langzeitkontrolle von 37 Patienten mit Diskusretrofixation im Zeitraum von 1986-1995.

Between January 1986 and December 1995 64 patients with anterior disc displacement were operated on, the technique being disc retrofixation. Follow-up of 37 patients was possible. Successful treatment was determined using the following criteria: one single operation, the clinical examination and the patient's opinion. The operative treatment was considered as unsuccessful if the patient had to undergo more than one operation or if, postoperatively, the clinical symptoms remained unchanged or even increased. 6 out of 37 patients were operated on twice or three times, another four patients postoperatively complained of unchanged or increased clinical symptoms. Using these criteria, disc retrofixation was ineffective in 30%. Using the correct anatomic position as an additional criterion of effective treatment, unsuccessful retrofixation would be even more than 30%. As a consequence we no longer recommend this technique.