Beneficial clinical effects but limited tissue quality following osteochondral repair with a cell-free multilayered nano-composite scaffold in the talus.

BACKGROUND: The treatment of larger osteochondral lesions of the talus remains an operative challenge. In addition to micro fracturing and osteochondral transplantation one promising strategy could be the operative repair with a cell-free multilayered nano-composite scaffold with the potential to regenerate bone and cartilage in one treatment. METHODS: In this prospective case series four consecutive patients who suffered from a single osteochondral lesion (≥1.5cm2) on the medial talus were enrolled. The repair potential of the implant was assessed using MRI based biochemical, compositional MR sequences (T2 mapping) as well as semi-quantitative morphological analyses (MOCART score) at 18 months follow-up after the surgery. The clinical outcome was determined at 6-, 12-, 18-, and 24 months follow-up by using the Ankle Disability Index and the AOFAS score. RESULTS: At 18 months after the surgery, the clinical outcome was significantly improved compared to the preoperative baseline. Global T2 relaxation times of the repair tissue were significantly increased compared to the healthy control cartilage. CONCLUSIONS: Osteochondral repair with a cell-free, biomimetic scaffold provides good clinical, short-term results. However, biochemical MR imaging provides strong evidence for limited repair tissue quality at 18 months after the implantation. LEVEL OF EVIDENCE: IV.

Successful osteoconduction but limited cartilage tissue quality following osteochondral repair by a cell-free multilayered nano-composite scaffold at the knee.

INTRODUCTION: The treatment of larger osteochondral lesions in the knee is still a clinical challenge. One promising strategy to overcome this problem could be surgical repair by using a cell-free multilayered nano-composite scaffold. METHOD: In this prospective cohort study eight consecutive patients which suffered from a single osteochondral lesion (≥1.5 cm(2)) on the femoral condyle were enrolled. The repair potential of the implant was assessed by using MRI based biochemical MR sequences (T2 mapping) as well as semi-quantitative morphological analyses (MOCART score) at 18 months after the surgery. The clinical outcome was determined at six, 12, 18, and 24 month follow ups by using IKDC, Tegner-Lysholm, and Cincinnati knee scores. RESULTS: Seven out of eight patients showed a complete integration of the scaffold into the border zone and five out of eight patients excellent or good subchondral ossification of the implant at 18 months following implantation. The surface of the repair tissue was found to be intact in all eight patients. T2 mapping data and the zonal T2 index significantly differed in the repair tissue compared to the healthy control cartilage (P < 0.001) which indicates a limited quality of the repair cartilage. The clinical outcome scores consistently improved during the follow up period without reaching statistical significance. CONCLUSIONS: Osteochondral repair by implanting the MaioRegen® scaffold provides a successful osteoconduction and filling of the cartilage defect. However there is evidence for a limited repair cartilage tissue quality at 18 months after the surgery.

Increased biological half-life of aerosolized liposomal recombinant human Cu/Zn superoxide dismutase in pigs.

Reactive oxygen species (ROS) are dangerous intermediates of cellular oxygen metabolisms, and are involved in pathogenesis of a wide range of diseases. Superoxide Dismutases (SODs) are an important part of antioxidant defense systems in mammalian cells capable of reducing the harmful effect of ROS on human tissues. Unfortunately, intravenously administered SOD shows a biological half-life of a few minutes, and enteral administration fails due to biodegradation of the enzyme in the gastrointestinal system. The aim of our study was to improve biological half-life of recombinant human Cu/Zn SOD (rhSOD) within systemic circulation by liposomal encapsulation and aerosolization into the lungs. We studied the feasibility of a "needle-free" route of drug administration via the lungs combined with the sustained release effect of liposomes in an experimental pig model. We studied 14 anesthetized pigs separated into three groups. The first group (n = 5) received 15 mg aerosolized liposomal rhSOD. The second group (n = 4) received 15 mg intravenously injected liposomal rhSOD. The third group (n = 5) served as an untreated control. We determined rhSOD concentration as well as activity within the lungs by the use of bronchoalveolar lavages (BALs). RhSOD plasma concentrations were determined by blood sampling. In animals treated with aerosolized liposomal rhSOD plasma concentration of the enzyme increased and formed a plateau ranging from 19 to 21 ng/mL over the whole observational period (5 h). At the end of the experiment 5 h after completion of aerosol administration 95.2% of peak plasma concentration was found in this group. Three and 5 h after completion of aerosolization leucocytes (p = 0.54, 0.40) in BALs as well as PaO2 (p = 0.44, 0.35), PaCO(2) (p = 0.83, 0.75), and pH (p = 0.07, 0.07) in arterial blood remained unchanged compared to baseline. In animals treated with intravenously injected liposomal rhSOD, plasma concentration of the enzyme substantially increased to 3987 ng/mL but rapidly decreased over the observational period (5 h). At the end of the experiment 14.1% of peak plasma concentration was found in this group. Aerosolization of liposomal rhSOD leads to long-term and uniform uptake into systemic circulation without acute deleterious effects on respiratory tract. Compared to intravenously administered liposomal rhSOD, biologic half-life within systemic circulation was substantially prolonged in aerosol-treated animals. It could be a feasible strategy for administration of radical scavenging enzymes for treatment of systemic diseases.