Hyaluronic acid (HA) is the major extracellular matrix component essential for the remarkable biomechanical functioning of cartilage and nucleus pulposus tissues in joint and disc spaces. The presence of hydrophilic moieties in HA helps in higher water retention capability that exerts internal swelling pressure to hydrate the tissues. For such reasons, HA injections are becoming popular to reduce friction and enhance lubrication in joints at the early onset of degeneration. Such injectable HA formulations are less invasive and exhibit a better reduction in pain. Yet, the retention of HA in the damaged tissue is extremely low due to its rapid degradation by the hostile microenvironment that attracts inflammatory cytokines and degradable enzymes. This necessitates recurrent administration of HA injections once every six months in clinical scenarios. In order to improve HA retention in the joint spaces, hyaluronic acid binding peptide (HABP) has emerged as a possible solution, as it can form non-covalent interaction with HA for better accumulation in vivo. However, administering HABP alone falls short in terms of maximizing lubrication, as native HA exists in the form of massive aggregates by binding and immobilizing highly polyanionic proteoglycans, a key hallmark for its ability to withstand compressive forces. However, during cartilage tissue degeneration, proteoglycans are cleaved by the inflammatory factors and MMPs; eventually, leading to loss of matrix hydration. Therefore, developing a synthetic macromolecular aggregate that recapitulates the native HA interactions with proteoglycans would enhance cartilage biomechanical properties and lubrication. Hence, the aim of my thesis is to synthesize and characterize HA-binding peptidoglycan mimics for enhanced therapeutic retention and lubrication at the articular surfaces of degenerated joints.