[Clinical trials as a central part of patient-centered clinical research].

As the continuation and implementation of findings from basic (pre‑)clinical research, clinical trials make a significant contribution to medical research. They form the central building block of translational medicine and thus make a decisive contribution to bringing medical knowledge into general care. This helps to make possible a healthcare system that is aligned to the needs of patients and functions efficiently in the long term.

[Clinical trials as a central part of patient-centered clinical research].

As the continuation and implementation of findings from basic (pre-)clinical research, clinical trials make a significant contribution to medical research. They form the central building block of translational medicine and thus make a decisive contribution to bringing medical knowledge into general care. This helps to make possible a healthcare system that is aligned to the needs of patients and functions efficiently in the long term.

Challenges for academic investigator-initiated pediatric trials for rare diseases.

Background: Clinical trials require great effort, time, expertise, and money. For clinicians at university hospitals with their full work load of teaching and medical care, the planning of an investigator-initiated clinical trial seems almost unthinkable. Despite their expertise in distinct diseases, university clinicians lack the time necessary to organize the funding and to initiate and conduct Phase III clinical trials in adults or in children.

Cell-free repair of small cartilage defects in the Goettinger minipig: the effects of BMP-7 continuously released by poly(lactic-co-glycolid acid) microspheres.

Objective: Cartilage repair of full-thickness chondral defects in the knees of Goettinger minipigs was assessed after treatment with cell-free collagen type-I gel with or without additional BMP-7 loaded poly(lactic-co-glycolid acid) microspheres.

Methods: Two full-thickness chondral defects were created in the trochlear groove of one hind leg knee in six Goettinger minipigs. Six defects were treated with a cell-free collagen type-I gel plug of 10 mm, the corresponding six defects were treated with a cell-free collagen type-I plug with poly(lactic-co-glycolid acid) microspheres loaded with recombinant BMP-7 (100 ng/ml gel).

Safety and Efficacy of the ACE-Inhibitor Ramipril in Alport Syndrome: The Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase III EARLY PRO-TECT Alport Trial in Pediatric Patients.

Introduction. Retrospective observational data show that ACE-inhibitor therapy delays renal failure and improves life expectancy in Alport patients with proteinuria. The EARLY PRO-TECT Alport trial assesses the safety and efficacy of early therapy onset with ramipril in pediatric Alport patients.

Simultaneous anabolic and catabolic responses of human chondrocytes seeded in collagen hydrogels to long-term continuous dynamic compression.

Cartilage repair strategies increasingly focus on the in vitro development of cartilaginous tissues that mimic the biological and mechanical properties of native articular cartilage. However, current approaches still face problems in the reproducible and standardized generation of cartilaginous tissues that are both biomechanically adequate for joint integration and biochemically rich in extracellular matrix constituents. In this regard, the present study investigated whether long-term continuous compressive loading would enhance the mechanical and biological properties of such tissues.

Cell-free repair of small cartilage defects in the Goettinger minipig: which defect size is possible?

Purpose: Cartilage repair of full-thickness chondral defects in the knees of Goettinger minipigs was assessed by treatment with cell-free collagen type-I gel plugs of three different sizes.

Methods: In 6 adult Goettinger minipigs, three full-thickness chondral defects were created in the trochlear groove of one knee of the hind leg. These defects were treated with a cell-free collagen type-I gel plug of 8, 10, or 12 mm diameter.

Bioreactor cultivation and remodelling simulation for cartilage replacement material.

For the development of articular cartilage replacement material, it is essential to study the dependence between mechanical stimulation and cell activity in cellular specimens. Bioreactor cultivation is widely used for this purpose, however, it is hardly possible to obtain a quantitative relationship between collagen type II production and applied loading history. For this reason, a bioreactor system is developed, measuring applied forces and number of loading cycles by means of a load cell and a forked light barrier, respectively.

A comparative study of 3 different cartilage repair techniques.

Purpose: The value of cell-free techniques in the treatment of cartilage defects remains under debate. In this study, cartilage repair of full-thickness chondral defects in the knees of Goettinger minipigs was assessed by treatment with a cell-free collagen type-I gel or a collagen type-I gel seeded with autologous chondrocytes. As a control, abrasion arthroplasty was included.

Condensed cellular seeded collagen gel as an improved biomaterial for tissue engineering of articular cartilage.

Three-dimensional autologous chondrocyte implantation based on collagen gel as matrix scaffold has become a clinically applied treatment for focal defects of articular cartilage. However, the low biomechanical properties of collagen gel makes intraoperative handling difficult and creates the risk of early damages to the vulnerable implant. The aim of the study was to create a stabilized form of collagen gel and to evaluate its biomechanical and biochemical properties.

[Electromagnetic fields, electric current and bone healing - what is the evidence?].

For more than 30 years the potential effects of electrical stimulation on bone healing have been investigated. Up to now this therapy is controversial and not established as a standardised treatment option. This systematic review and metaanalysis focuses on the potential effects of electromagnetic fields and high-frequency electric fields on bony healing.

Continuous cyclic compressive loading modulates biological and mechanical properties of collagen hydrogels seeded with human chondrocytes.

Purpose: This study investigated the potential of cyclic compressive loading in the generation of in vitro engineered cartilaginous tissue with the aim of contributing to a better understanding of mechanical preconditioning and its possible role in further optimizing existing matrix-associated cartilage replacement procedures.

Methods: Human chondrocytes were harvested from 12 osteoarthritic knee joints and seeded into a type I collagen (col-I) hydrogel at low density (2 × 10(5) cells/ml gel). The cell-seeded hydrogel was condensed and cultivated under continuous cyclic compressive loading (frequency: 0.

Effects of low concentration BMP-7 on human osteoarthritic chondrocytes: comparison of different applications.

While BMP-7 (OP-1) is one of the most potent growth factors in cartilage tissue engineering, the effects of exogenous low concentration BMP-7 on osteoarthritic chondrocytes are still unknown. Human osteoarthritic chondrocytes obtained from the femoral condyles of 10 patients were grown either in monolayer or in 3D collagen type-I gel culture in vitro. The growth factor was either given as a single dose of 50 ng/mL, a repeated dose, or continuously released from PGLA microspheres.

[Tissue engineering of cartilage replacement material - mechanical stimulation in the in-vitro cultivation of human chondrocytes].

The treatment of cartilage defects remains a major problem in orthopaedics. With regard to cartilage tissue engineering, the reimplantation of pre-cultivated chondrocytes in the form of a chondrocyte graft is a promising alternative to conventional methods. Clinical practice requires this MACT procedure (matrix-associated autologous chondrocyte transplantation) to produce a biocompatible replacement tissue with adequate mechanical properties.

Millicurrent stimulation of human articular chondrocytes cultivated in a collagen type-I gel and of human osteochondral explants.

Background: Here we investigate the effect of millicurrent treatment on human chondrocytes cultivated in a collagen gel matrix and on human osteochondral explants.

Methods: Human chondrocytes from osteoarthritic knee joints were enzymatically released and transferred into a collagen type-I gel. Osteochondral explants and cell-seeded gel samples were cultivated in-vitro for three weeks.

Effects of low concentrated BMP-7 administered by co-cultivation or plasmid transfection on human osteoarthritic chondrocytes.

Introduction: While BMP-7 has proven to be one of the most potent growth factors in cartilage tissue engineering, protein concentration and route of administration remain a matter of debate. Here we investigated the effects of a low concentration of BMP-7 on human osteoarthritic chondrocytes administered by protein co-cultivation and plasmid transfection.

Methods: Freshly released (P0) or in vitro propagated chondrocytes (P2) were cultivated in a collagen type-I gel for 3 weeks in vitro or in nude mice.

Effects of controlled released BMP-7 on markers of inflammation and degradation during the cultivation of human osteoarthritic chondrocytes.

The aim of the present study is to investigate the effects of BMP-7 released from polylactide microspheres on the appearance of various catabolic and inflammatory cytokines secreted by osteoarthritic chondrocytes cultivated in a collagen gel. Articular chondrocytes of 15 patients suffering from osteoarthritis are transferred to a collagen type-I gel. Additionally, BMP-7 encapsulated into polylactide microspheres (50 ng BMP-7/mL gel) is added.

BMP-7-loaded PGLA microspheres as a new delivery system for the cultivation of human chondrocytes in a collagen type I gel: the common nude mouse model.

Purpose: Bone morphogenic protein 7 (BMP-7) released from polylactide (PLGA) microspheres has proven to be a potent system in cartilage tissue engineering in vitro. However, in vivo data are still lacking. The aim of this study was to investigate this BMP-7 release system utilizing the nude mouse as a small animal model.

A cell-free collagen type I device for the treatment of focal cartilage defects.

The purpose of this study was to evaluate the potential value of a cell-free collagen type I gel plug for the treatment of focal cartilage defects. Cellular migration and proliferation was addressed in vitro, and the formation of repair tissue in a nude mouse-based defect model. A cell-free plug made of collagen type I was placed in the center of an incubation plate.

Ablation of articular cartilage with an erbium:YAG laser: an ex vivo study using porcine models under real conditions-ablation measurement and histological examination.

Background And Objectives: The use of an erbium:YAG laser in arthroscopic surgery has the advantage of a precise treatment of soft tissue. Due to the high absorption in water, the laser energy is perfectly matched to smoothing the hydrous, fibrillated articular cartilage surface. In minimal invasive surgery, the workspace is filled with aqueous liquids for enlargement.

[Optical coherence tomography (OCT) to evaluate cartilage tissue engineering].

Aim: The aim of this study was to investigate hyaline cartilage defects treated with cell-seeded artificial matrix systems (two different collagen type I gels) with the method of optical coherence tomography (OCT) and to correlate the results with conventional histological and immunocytochemical staining.

Method: Osteochondral blocks were harvested from 20 patients undergoing total knee replacement and trimmed to 2 x 2 cm. Under sterile conditions, chondral defects of 8 mm diameter were either filled with a collagen type I gel plug seeded with autologous chondrocytes (2 x 10 (5)/mL gel), or with a corresponding gel plug which was stabilised by a 20-fold compression.

Expression of ion channels of the TRP family in articular chondrocytes from osteoarthritic patients: changes between native and in vitro propagated chondrocytes.

The maintenance of a differentiated chondrocyte phenotype is influenced by several factors of which signal transduction of extracellular stimuli through the cell membrane is of major interest. One important group of membrane-bound proteins which are involved in transmembrane signal transduction are ion channels. Human articular chondrocytes were obtained from osteoarthritic femoral condyles.

Effects of pulsed and sinusoid electromagnetic fields on human chondrocytes cultivated in a collagen matrix.

Although several effects of electromagnetic fields (EMFs) on articular cartilage have been reported in recent studies, the use of EMFs to treat osteoarthritis remains a matter of debate. In an in vitro study, human chondrocytes harvested from osteoarthritic knee joints were released from their surrounding matrix and transferred in defined concentration into a 3D matrix (type-I collagen gel). The cultivation, performed under standard conditions, lasted up to 14 days.