The Anomalies of Hyaluronan Structures in Presence of Surface Active Phospholipids-Molecular Mass Dependence.

Interactions between hyaluronan (A-) and phospholipids play a key role in many systems in the human body. One example is the articular cartilage system, where the synergistic effect of such interactions supports nanoscale lubrication. A molecular dynamics simulation has been performed to understand the process of formation of hydrogen bonds inside the hyaluronan network, both in the presence and absence of phospholipids. Additionally, the effect of the molecular mass of (A-) was analyzed. The main finding of this work is a robust demonstration of the optimal parameters (H-bond energy, molecular mass) influencing the facilitated lubrication mechanism of the articular cartilage system. Simulation results show that the presence of phospholipids has the greatest influence on hyaluronan at low molecular mass. We also show the specific sites of H-bonding between chains. Simulation results can help to understand how hyaluronan and phospholipids interact at several levels of articular cartilage system functioning.

Molecular Dynamic Analysis of Hyaluronic Acid and Phospholipid Interaction in Tribological Surgical Adjuvant Design for Osteoarthritis.

Tribological surgical adjuvants constitute a therapeutic discipline made possible by surgical advances in the treatment of damaged articular cartilage beyond palliative care. The purpose of this study is to analyze interactions between hyaluronic acid and phospholipid molecules, and the formation of geometric forms, that play a role in the facilitated lubrication of synovial joint organ systems. The analysis includes an evaluation of the pathologic state to detail conditions that may be encountered by adjuvants during surgical convalescence. The synovial fluid changes in pH, hyaluronic acid polydispersity, and phospholipid concentration associated with osteoarthritis are presented as features that influence the lubricating properties of adjuvant candidates. Molecular dynamic simulation studies are presented, and the Rouse model is deployed, to rationalize low molecular weight hyaluronic acid behavior in an osteoarthritic environment of increased pH and phospholipid concentration. The results indicate that the hyaluronic acid radius of gyration time evolution is both pH- and phospholipid concentration-dependent. Specifically, dipalmitoylphosphatidylcholine induces hydrophobic interactions in the system, causing low molecular weight hyaluronic acid to shrink and at high concentration be absorbed into phospholipid vesicles. Low molecular weight hyaluronic acid appears to be insufficient for use as a tribological surgical adjuvant because an increased pH and phospholipid concentration induces decreased crosslinking that prevents the formation of supramolecular lubricating forms. Dipalmitoylphosphatidylcholine remains an adjuvant candidate for certain clinical situations. The need to reconcile osteoarthritic phenotypes is a prerequisite that should serve as a framework for future adjuvant design and subsequent tribological testing.

Hyaluronic acid and phospholipid interactions useful for repaired articular cartilage surfaces-a mini review toward tribological surgical adjuvants.

This mini review is focused on the emerging nexus between the medical device and pharmaceutical industries toward the treatment of damaged articular cartilage. The physical rationale of hyaluronic acid and phospholipid preparations as tribological surgical adjuvants for repaired articular cartilage surfaces is explored, with directions for possible new research which have arisen due to the therapeutic advance of the physiochemical scalpel. Because synovial joint lubrication regimes become dysfunctional at articular cartilage lesion sites as a result of the regional absence of the surface active phospholipid layer and its inability to reform without surgical repair, hyaluronic acid and phospholipid intra-articular injections have yielded inconsistent efficacy outcomes and only short-term therapeutic benefits mostly due to non-tribological effects. Parameters for hydrophobic-polar type interactions as applied to the lubricating properties of normal and osteoarthritic synovial fluid useful for repaired articular cartilage surfaces are discussed.

Some conceptual thoughts toward nanoscale oriented friction in a model of articular cartilage.

This work presents a conceptual framework as to how a deficit in the synovial-fluid content, exemplified by hyaluronan or any other amphiphilic species, is capable of decisively altering the complex lubrication and wear conditions observed clinically in articular cartilage. The effect is revealed in (non)stationary regimes if the cartilage is subjected to some normal periodic load, revealing over its exploitation time increasingly dissipative, in general entropy-addressing, characteristics. It can be hypothesized that a Grotthuss-type proton transport physiology-concerning mechanism in channel-like, phospholipid-water cartilage's articulating nanospaces will be responsible for the expression of the lubrication mode. The corresponding wear involving overall change is then manifested adequately in the stationary regime, and in a viable system-parametric correlation with its lubrication counterpart. Certain analytic formulae for the nanoscale oriented coefficient of friction, involving generically H-bonds breaking mechanism, and pointing to some local-viscosity context, have been proposed for fitting the experimental data and clinical observations involving proton management at articular cartilage surfaces.

Targeted In Situ Biosynthetic Transcriptional Activation in Native Surface-Level Human Articular Chondrocytes during Lesion Stabilization.

OBJECTIVE: Safe articular cartilage lesion stabilization is an important early surgical intervention advance toward mitigating articular cartilage disease burden. While short-term chondrocyte viability and chondrosupportive matrix modification have been demonstrated within tissue contiguous to targeted removal of damaged articular cartilage, longer term tissue responses require evaluation to further clarify treatment efficacy. The purpose of this study was to examine surface chondrocyte responses within contiguous tissue after lesion stabilization. METHODS: Nonablation radiofrequency lesion stabilization of human cartilage explants obtained during knee replacement was performed for surface fibrillation. Time-dependent chondrocyte viability, nuclear morphology and cell distribution, and temporal response kinetics of matrix and chaperone gene transcription indicative of differentiated chondrocyte function were evaluated in samples at intervals to 96 hours after treatment. RESULTS: Subadjacent surface articular cartilage chondrocytes demonstrated continued viability for 96 hours after treatment, a lack of increased nuclear fragmentation or condensation, persistent nucleic acid production during incubation reflecting cellular assembly behavior, and transcriptional up-regulation of matrix and chaperone genes indicative of retained biosynthetic differentiated cell function. CONCLUSIONS: The results of this study provide further evidence of treatment efficacy and suggest the possibility to manipulate or induce cellular function, thereby recruiting local chondrocytes to aid lesion recovery. Early surgical intervention may be viewed as a tissue rescue, allowing articular cartilage to continue displaying biological responses appropriate to its function rather than converting to a tissue ultimately governed by the degenerative material property responses of matrix failure. Early intervention may positively impact the late changes and reduce disease burden of damaged articular cartilage.

Native Chondrocyte Viability during Cartilage Lesion Progression: Normal to Surface Fibrillation.

OBJECTIVE: Early surgical intervention for articular cartilage disease is desirable before full-thickness lesions develop. As early intervention treatments are designed, native chondrocyte viability at the treatment site before intervention becomes an important parameter to consider. The purpose of this study is to evaluate native chondrocyte viability in a series of specimens demonstrating the progression of articular cartilage lesions to determine if the chondrocyte viability profile changes during the evolution of articular cartilage disease to the level of surface fibrillation. DESIGN: Osteochondral specimens demonstrating various degrees of articular cartilage damage were obtained from patients undergoing knee total joint replacement. Three groups were created within a patient harvest based on visual and tactile cues commonly encountered during surgical intervention: group 1, visually and tactilely intact surfaces; group 2, visually intact, tactilely soft surfaces; and group 3, surface fibrillation. Confocal laser microscopy was performed following live/dead cell viability staining. RESULTS: Groups 1 to 3 demonstrated viable chondrocytes in all specimens, even within the fibrillated portions of articular cartilage, with little to no evidence of dead chondrocytes. Chondrocyte viability profile in articular cartilage does not appear to change as disease lesion progresses from normal to surface fibrillation. CONCLUSIONS: Fibrillated partial-thickness articular cartilage lesions are a good therapeutic target for early intervention. These lesions retain a high profile of viable chondrocytes and are readily diagnosed by visual and tactile cues during surgery. Early intervention should be based on matrix failure rather than on more aggressive procedures that further corrupt the matrix and contribute to chondrocyte necrosis of contiguous untargeted cartilage.