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

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

Anomalous Behavior of Hyaluronan Crosslinking Due to the Presence of Excess Phospholipids in the Articular Cartilage System of Osteoarthritis

Lubrication of articular cartilage is a complex multiscale phenomenon in synovial joint organ systems. In these systems, synovial fluid properties result from synergistic interactions between a variety of molecular constituent. Two molecular classes in particular are of importance in understanding lubrication mechanisms: hyaluronic acid and phospholipids. The purpose of this study is to evaluate interactions between hyaluronic acid and phospholipids at various functionality levels during normal and pathological synovial fluid conditions. Molecular dynamic simulations of hyaluronic acid and phospholipids complexes were performed with the concentration of hyaluronic acid set at a constant value for two organizational forms, extended (normal) and coiled (pathologic). The results demonstrated that phospholipids affect the crosslinking mechanisms of hyaluronic acid significantly and the influence is higher during pathological conditions. During normal conditions, hyaluronic acid and phospholipid interactions seem to have no competing mechanism to that of the interaction between hyaluronic acid to hyaluronic acid. On the other hand, the structures formed under pathologic conditions were highly affected by phospholipid concentration