The Injection of Gels Through an Intact Annulus Maintains Biomechanical Performance without Extrusion Risk.

For autologous-disc-derived chondrocyte transplantation (ADCT) a transglutaminase crosslinked gelatine gel and an albumin hyaluronic acid gel, crosslinked with bis-thio-polyethylene glycol, were injected through a syringe into a degenerated intervertebral disc, where they solidified in situ. This biomechanical in vitro study with lumbar bovine motion segments evaluated disc height changes, motion characteristics in a quasi-static spine loading simulators, and the potential extrusion risk of these biomaterials in a complex dynamic multi-axial loading set-up with 100,000 loading cycles. After the injection and formation of the gel in the center of the nucleus, the disc height increase was about 0.

Hydrogel-Based Matrix-Associated Autologous Chondrocyte Implantation Shows Greater Substantial Clinical Benefit at 24 Months Follow-Up than Microfracture: A Propensity Score Matched-Pair Analysis.

Objective: To compare substantial clinical benefit (SCB) of a hydrogel-based, matrix-associated autologous chondrocyte implantation (M-ACI) method versus microfracture (MFx) in the treatment of knee cartilage defects.

Design: Propensity score matched-pair analysis, using the MFx control group of a phase III study as comparator for M-ACI treatment in a single-arm phase III study, resulting in 144 patients in the matched-pair set.

Results: Groups were comparable regarding baseline Knee Injury and Osteoarthritis Outcome Score (KOOS), sex, age, body mass index, symptom duration, smoking status, and previous knee surgeries.

Comparison of Hydrogel-Based Autologous Chondrocyte Implantation Versus Microfracture: A Propensity Score Matched-Pair Analysis.

Background: Few studies exist for large defects comparing matrix-associated autologous chondrocyte implantation (M-ACI) with other cartilage repair methods due to the limited availability of suitable comparator treatments.

Purpose: To compare the clinical efficacy of a novel hydrogel-based M-ACI method (NOVOCART Inject plus) versus microfracture (MFx) in patients with knee cartilage defects.

Study Design: Cohort study; Level of evidence, 3.

Cost-effectiveness of a new ACI technique for the treatment of articular cartilage defects of the knee compared to regularly used ACI technique and microfracture.

Aims: For patients with cartilage defects of the knee, a new biocompatible and cross-linkable albumin-hyaluronan-based hydrogel has been developed for matrix-associated autologous chondrocyte implantation (M-ACI) - NOVOCART Inject plus (Ninject; TETEC AG, Reutlingen, Germany). We aimed to estimate the potential cost-effectiveness of NInject, that is not available on the market, yet compared to spheroids of human autologous matrix-associated chondrocytes (Spherox; CO.DON GmbH, Leipzig, Germany) and microfracture.

Treatment of Large Cartilage Defects in the Knee by Hydrogel-Based Autologous Chondrocyte Implantation: Two-Year Results of a Prospective, Multicenter, Single-Arm Phase III Trial.

Objective: To evaluate the clinical outcome of a hydrogel-based autologous chondrocyte implantation (ACI) for large articular cartilage defects in the knee joint.

Design: Prospective, multicenter, single-arm, phase III clinical trial. ACI was performed in 100 patients with focal full-thickness cartilage defects ranging from 4 to 12 cm in size.

Characterization of primary chondrocytes harvested from hips with femoroacetabular impingement.

Objective: Acetabular chondral lesions are common in patients with femoroacetabular impingement (FAI) syndrome. The aim of this study was (1) to evaluate the proliferation potential of primary human chondrocytes (hC) derived from both acetabular and femoral site and (2) to validate cellular differentiation during three-dimensional (3D) cultivation as a prerequisite for autologous matrix-assisted cartilage regeneration of the hip joint.

Methods: hC were isolated from cartilage samples obtained from N = 6 patients during offset reconstruction.

Intervertebral disc cell- and hydrogel-supported and spontaneous intervertebral disc repair in nucleotomized sheep.

Purpose: Regenerative repair is a promising new approach in treating damaged intervertebral discs. An experimental scheme was established for autologous and/or allogenic repair after massive disc injury.

Methods: Disc healing was promoted in 11 animals by injecting in vitro expanded autologous/homologous disc cells 2 weeks after stab injury of lumbar discs L1-2.

Genomic chondrocyte culture profiling by array-CGH, interphase-FISH and RT-PCR.

Objective: In vitro expansion is an important step to acquire sufficient cells in human tissue engineering technologies. The high number of chondrocytes needed for human articular cartilage implants requires in vitro expansion of the primary cells, bearing a theoretical risk of in vitro induced changes in the genomes. To gain more insights into this situation, model cultures were prepared and analyzed.

Rheological and biological properties of a hydrogel support for cells intended for intervertebral disc repair.

Background: Cell-based approaches towards restoration of prolapsed or degenerated intervertebral discs are hampered by a lack of measures for safe administration and placement of cell suspensions within a treated disc. In order to overcome these risks, a serum albumin-based hydrogel has been developed that polymerizes after injection and anchors the administered cell suspension within the tissue.

Methods: A hydrogel composed of chemically activated albumin crosslinked by polyethylene glycol spacers was produced.

Hypoxic conditions during expansion culture prime human mesenchymal stromal precursor cells for chondrogenic differentiation in three-dimensional cultures.

Cell-based approaches using mesenchymal stromal precursor cells (MSCs) for the regeneration of intervertebral discs are attracting increased interest, even though the intervertebral disc is a very demanding environment. Implanted cells eventually face acidic pH, hypoxia, and a lack of nutrients. While the regenerative potential of MSCs for skeletal tissues has been well described, it is still questionable whether human MSCs can be prepared for prolonged survival and proper functioning and whether they can differentiate under the adverse conditions encountered in the disc.

[Perspectives of clinical stem cell therapy in the treatment of musculoskeletal diseases in Germany].

Aim: The treatment of large bone defects remains a challenge for the orthopaedic surgeon. Regenerative therapies with the use of mesenchymal stem cells (MSC) may provide an alternative to autogenous bone transplantation, callus distraction or the use of allografts.

Material And Methods: On the occasion of an expert workshop of the German Society for Orthopaedic and Trauma Surgery, a literature search regarding studies with the use of MSC was performed to evaluate its potential for future clinical studies.

Future perspectives of articular cartilage repair.

Extrapolating from the current state of the art in cartilage repair technology and basic science, we describe the future of regenerative medicine in the musculoskeletal system. Crucial milestones that have been recognized include supply with competent cells from autologous to xenogeneic sources, "intelligent" or "reactive" scaffold design, optimised application of humoral factors and the introduction of advanced gene-engineering technology. Besides these technical goals, ethical and legal considerations may significantly change the way pharmacological and medical components are recruited and regulated.

Growth and differentiation factors for cartilage healing and repair.

Chondrocyte differentiation and the maintenance of function requires both transient and long-lasting control through humoral factors, particularly under stress, repair and regeneration in vivo or in vitro as in cell and tissue culture. To date, humoral factors from all major classes of molecules are known to contribute: ions (calcium), steroids (estrogens), terpenoids (retinoic acid), peptides (PTHRP, PTH, insulin, FGFs) and complex proteins (IGF-1, BMPs). They may act indirectly through membrane receptors and signal pathways or directly on transcriptional control elements.

Articular cartilage defects in the knee--basics, therapies and results.

Full-thickness defects of the articular cartilage in the knee joint have lower regenerative properties than chondral lesions of the ankle. In order to avoid early osteoarthritis, symptomatic articular cartilage defects in younger patients should undergo biological reconstruction as soon as possible. Various surgical procedures are available to biologically resurface the articular joint line.

Chondrogenic potential of human adult mesenchymal stem cells is independent of age or osteoarthritis etiology.

Osteoarthritis (OA) is a multifactorial disease strongly correlated with history of joint trauma, joint dysplasia, and advanced age. Mesenchymal stem cells (MSCs) are promising cells for biological cartilage regeneration. Conflicting data have been published concerning the availability of MSCs from the iliac crest, depending on age and overall physical fitness.

Comparison of marker gene expression in chondrocytes from patients receiving autologous chondrocyte transplantation versus osteoarthritis patients.

Currently, autologous chondrocyte transplantation (ACT) is used to treat traumatic cartilage damage or osteochondrosis dissecans, but not degenerative arthritis. Since substantial refinements in the isolation, expansion and transplantation of chondrocytes have been made in recent years, the treatment of early stage osteoarthritic lesions using ACT might now be feasible. In this study, we determined the gene expression patterns of osteoarthritic (OA) chondrocytes ex vivo after primary culture and subculture and compared these with healthy chondrocytes ex vivo and with articular chondrocytes expanded for treatment of patients by ACT.

[Cartilage repair in the knee joint].

Full thickness defects of the articular cartilage in the knee joint have lower regenerative properties compared to chondral lesions of the ankle. In order to avoid early osteoarthritis, symptomatic articular cartilage defects in younger patients should undergo biological reconstruction as early as possible. There are different surgical procedures available to achieve a biological resurfacing of the articular joint line.

Human anulus fibrosis and nucleus pulposus cells of the intervertebral disc: effect of degeneration and culture system on cell phenotype.

Study Design: Human intervertebral disc cells were harvested from patients with adolescent idiopathic scoliosis (AIS) and from donors with degenerative disc disease. Anulus fibrosis (AF) was separated from nucleus pulposus (NP), and cells were cultured separately in two different cell culture models.

Objectives: To investigate changes in gene expression of human disc cells during in vitro expansion and to determine whether cells from adolescent idiopathic scoliosis donors show different gene expression profiles compared with cells from patients operated for degenerative disc disease.

[Significance and technique of autologous chondrocyte transplantation].

The bad risk for an early onset of osteoarthritis in the knee increases with the size of a cartilage defect. A collateral meniscus- or ligament-tear will enforce this hazard in addition. In order to avoid such a development, relevant full-thickness cartilage defects should be reconstructed biologically and attendant meniscus- or ligament-tears as well as varus- or valgus deformities should be treated.

Effect of human platelet supernatant on proliferation and matrix synthesis of human articular chondrocytes in monolayer and three-dimensional alginate cultures.

Articular cartilage is rich in collagen type II fibres and proteoglycans and is characterized by low cell density. Chondrocytes have specific nutritional requirements and therefore cannot be expanded in vitro without the risk of generating fibroblastoid cells expressing type I collagen. Therefore, various growth conditions were tested for cartilage tissue engineering.

[Indications and implementation of recommendations of the working group "Tissue Regeneration and Tissue Substitutes" for autologous chondrocyte transplantation (ACT)].

For the treatment of full-thickness articular cartilage lesions of the knee joint, as a result of trauma or osteochondritis dissecans, a variety of biological reconstruction techniques have been developed. Different studies, some of which were performed as randomised, prospective clinical studies, showed that the autologous chondrocyte transplantation (ACT) provides the most satisfying and reliable method of cartilage reconstruction in the adult when applied to defects exceeding 4 cm (2). Based on these results, ACT seems to be of economic benefit, as the risk of developing osteoarthritis correlates significantly with the size of the cartilage defect, when not treated properly and in time.

Bone morphogenetic protein (BMP)-2 enhances the expression of type II collagen and aggrecan in chondrocytes embedded in alginate beads.

Objective: For autologous chondrocyte transplantation (ACT) chondrocytes are expanded in vitro. During expansion these cells may dedifferentiate. This change in phenotype is characterized by a raised expression of type I collagen and a decrease in type II collagen expression.