Hydrogel-based autologous chondrocyte implantation leads to subjective improvement levels comparable to scaffold based autologous chondrocyte implantation.

PURPOSE: Scaffold-based autologous chondrocyte implantation is a well-established treatment for cartilage defects in the knee joint. Hydrogel-based autologous chondrocyte implantation using an in situ polymerizable biomaterial is a relatively new treatment option for arthroscopic cartilage defects. It is therefore important to determine if there are significant differences in the outcomes. The aim of this study is to compare the outcomes (using subjective parameters) of hydrogel-based autologous chondrocyte implantation (NOVOCART® Inject) with the outcomes of scaffold based autologous chondrocyte Implantation (NOVOCART® 3D) using biphasic collagen scaffold. METHODS: The data of 50 patients, which were paired with 25 patients in each treatment group, was analyzed. The main parameters used for matching were gender, number of defects and localization. Both groups were compared based on Visual Analogue Scale (VAS) and subjective IKDC scores, both of which were examined pre-operatively and after 6, 12 and 24 months. RESULTS: Significant benefits in both VAS and IKDC scores after 2 years of follow-up in both groups were found. Comparing the groups, the results showed that in the hydrogel-based autologous chondrocyte implantation group, significant changes in IKDC scores are measurable after 6 months, while it takes 12 months until they are seen in the scaffold based autologous chondrocyte group. CONCLUSION: Hydrogel-based autologous chondrocyte and scaffold based autologous chondrocyte show comparable improvements and significant benefits to the patients' subjective well-being after a 2-year-follow-up. LEVEL OF EVIDENCE: III.

Third-generation autologous chondrocyte implantation after failed bone marrow stimulation leads to inferior clinical results.

PURPOSE: Third-generation autologous chondrocyte implantation (ACI) is an established and frequently used method and successful method for the treatment of full-thickness cartilage defects in the knee. There are also an increasing number of patients with autologous chondrocyte implantation as a second-line therapy that is used after failed bone marrow stimulation in the patient's history. The purpose of this study is to investigate the effect of previous bone marrow stimulation on subsequent autologous chondrocyte implantation therapy. In this study, the clinical results after the matrix-based autologous chondrocyte implantation in the knee in a follow-up over 3 years postoperatively were analysed. METHODS: Forty patients were included in this study. A total of 20 patients with cartilage defects of the knee were treated with third-generation autologous chondrocyte implantation (Novocart® 3D) as first-line therapy. The mean defect size was 5.4 cm2 (SD 2.6). IKDC subjective score and VAS were used for clinical evaluation after 6, 12, 24 and 36 months postoperatively. The results of these patients were compared with 20 matched patients with autologous chondrocyte implantation as second-line therapy. Matched pair analysis was performed by numbers of treated defects, defect location, defect size, gender, age and BMI. RESULTS: Both the first-line (Group I) and second-line group (Group II) showed significantly better clinical results in IKDC score and VAS score in the follow-up over 3 years compared with the preoperative findings. In addition, Group I showed significantly better results in the IKDC and VAS during the whole postoperative follow-up after 6, 12, 24 and 36 months compared to Group II with second-line autologous chondrocyte implantation (IKDC 6 months p = 0.015, 1 year p = 0.001, 2 years p = 0.001, 3 years p = 0.011). Additionally, we found a lower failure rate in Group I. No revision surgery was performed in Group I. The failure rate in the second-line Group II was 30%. CONCLUSION: This study showed that third-generation autologous chondrocyte implantation is a suitable method for the treatment of full-thickness cartilage defects. Both, Group I and Group II showed significant improvement in our follow-up. However, in comparing the results of the two groups, autologous chondrocyte implantation after failed bone marrow stimulation leads to worse clinical results. LEVEL OF EVIDENCE: III.

The effect of autologous Achilles bursal tissue implants in tendon-to-bone healing of rotator cuff tears in rats.

BACKGROUND: The aim of this study was to investigate the influence of autologous bursal tissue derived from the Achilles bursa on tendon-to-bone healing after rotator cuff tear repair in a rat model. METHODS: A total of 136 Sprague-Dawley rats were randomly assigned to either an untreated or a bursal tissue application group or biomechanical testing and histologic testing after rotator cuff repair. After separating the supraspinatus tendon close to the greater tuberosity, the tendon was reattached either unaltered or with a bursal tissue interposition sewn onto the interface. Immunohistologic analysis was performed 1 and 7 weeks after supraspinatus tendon reinsertion. Biomechanical testing of the tendon occurred 6 and 7 weeks after reinsertion. RESULTS: Immunohistologic results demonstrated a significantly higher percentage of Type II collagen (P = .04) after 1 and 7 weeks in the tendon-to-bone interface using autologous bursal tissue in comparison to control specimens. The bursa group showed a significantly higher collagen I to III quotient (P = .03) at 1 week after surgery in comparison to the 7-week postsurgery bursa groups and controls. Biomechanical assessment showed that overall tendon stiffness (P = .002) and the tendon viscoelasticity in the bursa group (P = .003) was significantly improved after 6 and 7 weeks. There was no significant difference (P = .55) in force to failure between the bursa group and the control group after 6 and 7 weeks. CONCLUSION: Autologous bursal tissue derived from the Achilles bursa and implanted to the tendon-to-bone interface after rotator cuff repair facilitates a faster healing response to re-establish the biologic and biomechanical integrity of the rotator cuff in rats.

Cell Toxicity in Fibroblasts, Tenocytes, and Human Mesenchymal Stem Cells-A Comparison of Necrosis and Apoptosis-Inducing Ability in Ropivacaine, Bupivacaine, and Triamcinolone.

PURPOSE: To analyze the ability of ropivacaine, bupivacaine, and triamcinolone to induce apoptosis and necrosis in fibroblasts, tenocytes, and human mesenchymal stem cells. METHODS: Human dermal fibroblasts, adipose-derived human mesenchymal stem cells (hMSCs), and tenocytes gained from the rotator cuff tendon were seeded with a cell density of 0.5 × 104/cm2. One specimen of ropivacaine, bupivacaine, and triamcinolone was tested separately on the cells with separate concentrations of 0.5%, 0.25%, and 0.125% for each specimen. The negative control received no agent, only a change of medium. The incubation period for each agent was 30 minutes. After a change of medium and 1 hour, 24 hours, and 7 days of incubation, 104 cells were harvested and analyzed via fluorescence-activated cell sorting with double-staining with annexin V and propidium iodide. Statistical analysis to determine significant difference (P < .05) between the groups with SPSS statistics 23 through one-way analysis of variance with a univariate general linear model was performed. RESULTS: Bupivacaine showed necrosis-inducing effects on fibroblasts and tenocytes, with the necrotic effect peaking at 0.5% and 0.25%. Ropivacaine and triamcinolone caused no significant necrosis. Compared with fibroblasts and tenocytes, hMSCs did not show significant necrotic or apoptotic effects after exposure to bupivacaine. Overall, no significant differences in apoptosis were detected between different cell lines, varying concentrations, or time measurements. CONCLUSIONS: Bupivacaine 0.5% and 0.25% have the most necrosis-inducing effects on fibroblasts and tenocytes. Ropivacaine caused less necrosis than bupivaine. Compared with fibroblasts and tenocytes, hMSCs were not affected by necrosis using any of the tested agents. A significant apoptosis-inducing effect could not be detected for the different cell lines. CLINICAL RELEVANCE: Possible cell toxicity raises questions of concern for intra-articular injections using local anesthetics and corticosteroids. The present study demonstrates the necrotic and apoptotic effects of ropivacaine, bupivacaine, and triamcinolone and may give recommendations for intra-articular use of local anesthetics and corticosteroids.

Rotator Cuff Repair With Autologous Tenocytes and Biodegradable Collagen Scaffold: A Histological and Biomechanical Study in Sheep.

BACKGROUND: Large rotator cuff tears still represent a challenging problem in orthopaedics. The use of tenocytes on biomaterials/scaffolds for the repair of large rotator cuff defects might be a promising approach in the field of tendon regeneration. HYPOTHESIS: Cultivated autologous tenocytes seeded on a collagen scaffold lead to enhanced histological and biomechanical results after rotator cuff repair in a sheep model as compared with unseeded scaffolds in an acute setting. STUDY DESIGN: Controlled laboratory study. METHODS: At the tendon-bone junction of the infraspinatus tendon of the right foreleg of 24 sheep, a 3.5 × 1.5-cm tendon defect was created. Sheep were randomly allocated to group 1, a defect; group 2, where an unseeded collagen scaffold was implanted; or group 3, which received the implantation of a collagen scaffold seeded with autologous tenocytes. Twelve weeks postoperatively, tendon regeneration was examined histologically and biomechanically. RESULTS: The histology of the neotendons of group 3 showed better fiber patterns, a higher production of proteoglycans, and an increased genesis of collagen III in contrast to groups 1 and 2. Immunostaining revealed less tissue dedifferentiation, a more structured cartilage layer, and homogeneous cartilage-bone transition in group 3 in comparison with groups 1 and 2. Biomechanically, the tensile strength of the reconstructed tendons in group 3 (mean load to failure, 2516 N; SD, 407.5 N) was approximately 84% that of the native tendons (mean load to failure, 2995 N; SD, 223.1 N) without statistical significance. A significant difference (P = .0095) was registered between group 1 (66.9% with a mean load to failure of 2004 N; SD, 273.8 N) and the native tendons, as well as between group 2 (69.7% with a mean load to failure of 2088 N; SD, 675.4 N) and the native tendons for mean ultimate tensile strength. In breaking stress, a significant difference (P = .0095) was seen between group 1 (mean breaking stress, 1335 N/mm2; SD, 182.7 N/mm2) and the native tendons, as well as between group 2 (breaking stress, 1392 N/mm2; SD, 450.2 N/mm2) and the native tendons (mean breaking stress, 1996 N/mm2; SD, 148.7 N/mm2). Again, there was no significant difference between group 3 (mean breaking stress, 1677 N/mm2; SD, 271.7 N/mm2) and the native tendons. CONCLUSION: Autologous tenocytes seeded on collagen scaffolds yield enhanced biomechanical results after tendon-bone reconstruction as compared with unseeded scaffolds in an acute setting. Biomechanical results and histological outcomes were promising, showing that the use of autologous tenocytes with specific carrier matrices could be a novel approach for repairing rotator cuff tears. CLINICAL RELEVANCE: This study supports the use of tenocytes and scaffolds for improving the quality of tendon-bone regeneration.

Migration of Mesenchymal Stem Cells of Bursal Tissue after Rotator Cuff Repair in Rats.

Purpose The purpose of this study is to verify migration of mesenchymal stem cells of bursal tissue into the healing site after rotator cuff repair in rats. Methods Fischer rats and green fluorescent protein (GFP)-transgenic rats were used. Bursal tissue from GFP rats was isolated and transplanted into tendon repair sites in Fischer rats. We examined the histology of the rotator cuff and the proportion of GFP-positive cells in the repaired rotator cuff 1, 3, and 6 weeks after surgery. Results Cell migration was observed during the third and sixth week after surgery. We also found mesenchymal stem cells and formed bursal cluster patterns in the repaired rotator cuff tendons. Conclusion Mesenchymal stem cells migrated from bursal tissue and infiltrated the repaired rotator cuff tendons. Clinical Relevance Mesenchymal stem cells from bursal tissue can contribute to the healing progress of the repaired rotator cuff.

Spinal cord damage after resection of destructive spinal lipoma resembling liposarcoma: case report.

A 39-year-old inpatient at a tumor orthopedic department with a history of a chondrosarcoma in the scapula presented with a destructive tumorous lesion in the staging computed tomography (CT). After ambiguous results in CT-guided biopsy and an open biopsy, a surgical removal of a tumorous lesion was performed. The histological findings showed a lipoma of the spine. Intraosseous lipomas with predisposition to pathological fracture or compression of the spinal cord with neurological symptoms should be removed. We report a case in which the patient presented with complete paraplegia due to an edema in the spinal cord immediately after removal surgery. The necessity of resection of a spinal lipoma with postoperative spinal cord damage needs to be discussed. To our knowledge, this case is one of the first to demonstrate that the diagnosis of tumors of the vertebra should be carefully evaluated and possible spinal cord damage as a complication should be kept in mind upon deciding on further therapies and interventions.