Christian Albrecht

The influence of scaffold architecture on chondrocyte distribution and behavior in matrix-associated chondrocyte transplantation grafts.

Scaffold architecture and composition are important parameters in cartilage tissue engineering. In this in vitro study, we compared the morphology of four different cell-graft systems applied in clinical cartilage regeneration and analyzed the cell distribution (DAPI nuclei staining) and cell-scaffold interaction (SEM, TEM). Our investigations revealed major differences in cell distribution related to scaffold density, pore size and architecture. Material composition influenced the quantity of autogenous matrix used for cellular adhesion. Cell bonding was further influenced by the geometry of the scaffold subunits. On scaffolds with widely spaced fibers and a thickness less than the cell diameter, chondrocytes surrounded the scaffold fibers with cell extensions. On those fibers, chondrocytes were spherical, suggesting a differentiated phenotype. Fiber sizes smaller than chondrocyte size, and widely spaced, are therefore beneficial in terms of improved adhesion by cell shape adaptation. They also support the differentiated stage of chondrocytes by preventing the fibroblast-like and polygonal cell shape, at least briefly.

Strongly enhanced levels of sclerostin during human fracture healing

Sclerostin (SOST), an antagonist of Wnt signaling, is an important negative regulator of bone formation. However, no data on the role of SOST in the human fracture healing have been published so far. This study addressed this issue. Seventy‐five patients with long bone fractures were included into the study and divided in two groups. The first group contained 69 patients with normal fracture healing. Six patients with impaired fracture healing formed the second group. Thirty‐four volunteers donated blood samples as control. Serum samples were collected over a period of 1 year following a standardized time schedule. In addition, SOST levels were measured in fracture hematoma and serum of 16 patients with bone fractures. Fracture hematoma contained significantly higher SOST concentrations compared to patients serum. SOST levels in fracture hematoma and in patients serum were both significantly higher than in the serum of controls. Highly elevated SOST serum concentrations were found in patients with physiological fracture healing. SOST levels were decreased in patients with impaired fracture healing. However, this difference was not statistically significant. This is the first study to provide evidence of strongly enhanced SOST levels in patients with bone fracture. The results indicate local and systemic involvement of SOST in humans during fracture healing.

Results 2 Years After Matrix-Associated Autologous Chondrocyte Transplantation Using the Novocart 3D Scaffold An Analysis of Clinical and Radiological Data

Background: A range of scaffolds is available from various manufacturers for cartilage repair through matrix-associated autologous chondrocyte transplantation (MACT), with good medium- to long-term results. Purpose: To evaluate clinical and magnetic resonance imaging (MRI) outcomes 2 years after MACT on the knee joint using the Novocart 3D scaffold based on a bilayered collagen type I sponge. Study Design: Case series; Level of evidence, 4. Methods: Of 28 initial patients, 23 were clinically and radiologically evaluated 24 months after transplantation. Indications for MACT were chondral or osteochondral lesions on the knee joint with a defect size >2 cm2, no instability, and no malalignment (axis deviation <5°). Then, MRI was performed on a 3-T scanner to assess the magnetic resonance observation of cartilage repair tissue (MOCART) and 3-dimensional (3D) MOCART scores. A variety of subjective scores (International Knee Documentation Committee [IKDC], Knee injury and Osteoarthritis Outcome Score [KOOS], Noyes sports activity rating scale, Tegner activity scale, and visual analog scale [VAS] for pain) were used for clinical evaluation. Results: Two years after MACT, the MRI evaluation showed a mean MOCART score of 73.2 ± 12.4 and a 3D MOCART score of 73.4 ± 9.7. Clinical results showed mean values of 69.8 ± 15.2 for the IKDC; 51.6 ± 21.2, 86.5 ± 13.9, 54.5 ± 23.6, 65.0 ± 8.0, and 91.5 ± 10.6 for the KOOS subscales (Quality of Life, Pain, Sports and Recreation, Symptoms, and Activities of Daily Living, respectively); 77.5 ± 12.7 for the Noyes scale; 4.4 ± 1.6 for the Tegner activity scale; and 1.8 ± 1.7 for the VAS, with statistically significant improvement in all scores other than KOOS-Symptoms. Conclusion: Undergoing MACT using the Novocart 3D scaffold is an applicable method to treat large focal chondral and osteochondral defects, with good short-term clinical and radiological results.

Clinical and Radiological Long-term Outcomes After Matrix-Induced Autologous Chondrocyte Transplantation A Prospective Follow-up at a Minimum of 10 Years

Background: It is unclear whether matrix-associated autologous chondrocyte transplantation (MACT) results in objective and subjective clinical improvements at 10 years after surgery. Hypothesis: Matrix-associated autologous chondrocyte transplantation will result in clinical and radiological improvements in patients with symptomatic, traumatic chondral defects of the knee joint. Study Design: Case series; Level of evidence, 4. Methods: A total of 16 patients with chondral defects of the knee were treated with MACT between November 2000 and April 2002 and evaluated for up to 10 years after the intervention. The International Knee Documentation Committee (IKDC) form, Knee Injury and Osteoarthritis Outcome Score (KOOS), Tegner activity score, Brittberg score, Noyes sports activity rating scale, and visual analog scale (VAS) for pain as well as 3-T magnetic resonance imaging (MRI) using the magnetic resonance observation of cartilage repair tissue (MOCART) score and functional evaluation by the limb symmetry index (LSI) formed the basis of this study. The Friedman test and the Wilcoxon signed-rank test were performed for a comparison between all time points and 2 separate time points, respectively. If significant differences were revealed, a Bonferroni adjustment to the α level was applied so that P values <.007 (<.05/7) were regarded as significant in the paired comparisons. Results: Significant improvements (P < .05) from baseline to 120 months postoperatively were observed for the IKDC score (mean, 44.1 ± 26.9 to 59.0 ± 27.4), Noyes sports activity rating score (mean, 37.7 ± 30.1 to 62.1 ± 31.3), and KOOS Quality of Life and Pain subscores, whereas no statistically significant improvement was detected for the Brittberg score, Tegner activity score, or VAS score. After 5 years, a slight downward tendency of all clinical scores was evident. After 10 years, the mean MOCART score was 70.4 ± 16.1. Complete filling of the defect was observed in 73.9% of cases, and osteophytes were present in 78.3%. In 65.2% of the cases, a subchondral bone edema <1 cm was visible, whereas in 21.7% of the cases, a subchondral bone edema >1 cm was seen. The mean LSI for the single-legged hop test was 95.6% ± 16.2% and for the triple hop test for distance was 91.3% ± 12.2%. The mean VAS score for self-perceived stability was 60.2 ± 3.5 (range, 0-9.5) for the injured and 60.7 ± 3.8 (range, 0-10) for the uninjured leg. No adhesions or effusions were seen regarding the clinical and radiological outcomes. Conclusion: The significantly improved results on 3 outcome measures after 10 years suggest that MACT represents a suitable option in the treatment of local cartilage defects in the knee.

Ability to Return to Sports 5 Years After Matrix-Associated Autologous Chondrocyte Transplantation in an Average Population of Active Patients

Background: Cartilage injuries often occur during sports activities, and return to sports after cartilage surgery is an important outcome parameter for different treatment methods in the competitive as well as the recreationally active population. Hypothesis: At the time of midterm follow-up after matrix-associated autologous chondrocyte transplantation (MACT), return to recreational sports at the preinjury level will be possible. Study Design: Case series; Level of evidence, 4. Methods: Seventy patients (51 men, 19 women; age [mean ± standard deviation], 34.9 ± 8.6 y; range, 18-55 y) were clinically evaluated 5 years after MACT through subjective clinical scores such as the Knee Injury and Osteoarthritis Outcome Score (KOOS) sport and recreation subscales, the Tegner activity scale, and the Noyes sports activity rating scale. The level of sports participation was included in the investigation. Results: The results 5 years after MACT showed mean values of 60.1 for the KOOS–sport, 67.4 for the Noyes, and 3.8 for the Tegner scores, meaning that regular sports activity such as cycling or running on flat ground, as well as medium-level manual labor, is possible. We noted that 74.3% of our patients returned to at least their preinjury sports level. Conclusion: Midterm postoperative results after MACT show that in a moderately active population, participation in regular sports is possible for most patients, at least at their preinjury recreational level and intensity, and there is a good rate of return to sports.

IGF expression patterns and regulation in growth plate chondrocytes

IGF-I and IGF-II are key regulators of growth and metabolism. Still, data about their expression and distribution within the growth plate in different animal models remain contradictory. Inferences drawn from rodent animal models can only be applied to human conditions to a limited extent as the rodents growth plate never fuses. In this study, we compared the expression of IGF-I and IGF-II in native growth plates of prepubertal piglets and under different cell culture conditions. We detected IGF-I mRNA expression and abundantly expressed IGF-II within the growth plate. IGF-I expression increased during monolayer cell culture while IGF-II expression dramatically decreased. Our studies revealed that these expression patterns remained unaffected by growth hormone stimulation in vitro. The abundant expression of IGF-II in porcine growth plate tissue, both on the mRNA and on the protein level, suggests that IGF-II also has a role in growth regulation at the early postnatal stage.

Influence of Cell Differentiation and IL-1β Expression on Clinical Outcomes After Matrix-Associated Chondrocyte Transplantation

Background: Several patient- and defect-specific factors influencing clinical outcomes after matrix-associated chondrocyte transplantation (MACT) have been identified, including the patient’s age, location of the defect, or duration of symptoms before surgery. Little is known, however, about the influence of cell-specific characteristics on clinical results after transplantation. Purpose: The aim of the present study was to investigate the influence of cell differentiation and interleukin-1 β (IL-1β) expression on clinical outcomes up to 5 years after MACT. Study Design: Case series; Level of evidence, 4. Methods: Twenty-seven patients who underwent MACT of the tibiofemoral joint area of the knee were included in this study. Clinical assessments were performed preoperatively as well as 6, 12, 24, and 60 months after transplantation by using the following scores: the Knee injury and Osteoarthritis Outcome Score (KOOS), the International Knee Documentation Committee (IKDC) Subjective Knee Form, the Noyes sports activity rating scale, the Brittberg clinical score, and a visual analog scale (VAS) for pain. The quality of repair tissue was assessed by magnetic resonance imaging using the magnetic resonance observation of cartilage repair tissue (MOCART) score at 1 and 5 years. Cell differentiation (defined as collagen type II:type I expression ratio), aggrecan, and IL-1β expression were determined by real-time polymerase chain reaction in transplant residuals and were correlated with clinical outcomes. Results: The largest improvements in clinical scores were found during the first year. Two years postoperatively, a stable improvement was reached until 5 years after transplantation, with a mean IKDC score of 34.4 ± 8.6 preoperatively to 77.9 ± 16 after 24 months (P < .001). Cell differentiation showed a significant positive correlation with nearly all clinical scores at different time points, especially after 12 months (P < .05). IL-1β expression negatively influenced clinical outcomes at 24 months (Brittberg score) and 60 months (Brittberg and VAS scores) after surgery (P < .05). No correlation was found between the MOCART score and clinical outcomes or gene expression. Conclusion: Our data demonstrate that cell differentiation and IL-1β expression influence clinical outcomes up to 5 years after MACT.

Risk factors for humeral head necrosis and non-union after plating in proximal humeral fractures

AIM The aim of this study was to evaluate risk factors for the development of humeral head necrosis and non-union after proximal humeral fractures-in particular, general risk factors that exist independent of fracture type. MATERIALS AND METHODS This study included patients (n=154) treated for proximal humeral fracture by means of open reduction and internal fixation (ORIF) using the Philos plate at a single level I trauma centre between January 2005 and December 2013. Follow-up monitoring included radiographic examination before hospital discharge, and again at 6 weeks, 12 weeks, and 6 months after surgery. At a minimum follow-up time of 6 months, radiographs taken in the anteroposterior and axial projection were evaluated in regard to the development of humeral head necrosis, non-union, and secondary screw cut out. RESULTS A total of 154 patients (61 males, 93 females) were available for radiological checkup. Mean age was 55.8 years (range: 19-91 years). There were statistically significant correlations between the development of avascular necrosis (AVN) and fracture type, non-union and smoking, and screw cut out - as well as overall complication rate - and age. The time to surgery did not influence the risk for AVN or non-union, independent of fracture type. In this study population, the risk of developing non-union after ORIF was 3.9-fold higher in heavy smokers (i.e., >20 cigarettes per day). The risk for screw cut out was 4.1-fold higher in patients over 60 years of age, and the overall risk for complications was 3.3-fold higher. CONCLUSION The older the patient, the more carefully one must consider the decision between conservative and operative treatments. If surgical treatment is performed, screw length should be selected depending on the patients age. Heavy smokers must be informed preoperatively of the increased risk for bony non-union after ORIF.

Neurofilament distribution in the superior labrum and the long head of the biceps tendon

BackgroundThe postoperative course after arthroscopic superior labrum anterior to posterior (SLAP) repair using suture anchors is accompanied by a prolonged period of pain, which might be caused by constriction of nerve fibres. The purpose was to histologically investigate the distribution of neurofilament in the superior labrum and the long head of the biceps tendon (LHBT), i.e. the location of type II SLAP lesions.MethodsTen LHBTs including the superior labrum were dissected from fresh human specimen and immunohistochemically stained against neurofilament (NF). All slides were scanned at high resolution and converted into tagged image file format, and regions of interest (ROIs) were defined as follows: ROI I—superior labrum anterior to the LHBT origin, ROI II—mid-portion of the superior labrum at the origin of the LHBT, ROI III—superior labrum posterior to the LHBT origin and ROI IV—the most proximal part of the LHBT before its attachment to the superior labrum. The entire images were automatically segmented according to the defined ROIs and measured using a programmed algorithm specifically created for this purpose. The NF-positive cells were counted, and their total size and the area of other tissue were measured separately for the different ROIs.ResultsDistribution of NF-positive cells in absolute numbers revealed a clear but insignificantly higher amount in favour of ROI I, representing the superior labrum anterior to the LHBT origin. Setting ROI I at 100%, a significant difference could be seen compared to ROI III, representing the superior labrum posterior to the LHBT origin (ROI I vs. ROI III with a p value < 0.05).ConclusionsSummarizing, the density of neurofilament is inhomogeneously distributed throughout the superior labrum with the highest number of neurofilament in the anterior superior labrum. Thus, suture placement in type II SLAP repair could play an important role for the postoperative pain-related outcome.