Post-traumatic osteoarthritis (PTOA) is a degenerative disease characterized by changes in articular cartilage, subchondral bone, and synovial tissues due to an acute injury to the joint. Lubricin, a highly conserved mucin-like glycoprotein, is one of the major bio lubricants in the joint and plays a crucial role in maintaining joint homeostasis. However, despite the severe and early osteoarthritic changes observed in human patients lacking functional lubricin, there is no consensus as to how synovial fluid lubricin is altered in response to joint trauma and subsequent PTOA. Yet, numerous studies testing genetic overexpression or intra-articular supplementation of lubricin have shown benefits in rodent models. Thus, there is continued interest in developing full-length, glycosylated lubricin as not only therapeutic for PTOA but also as a bio-lubricant and anti-fouling agent. Here, we demonstrated a strategy to utilize codon redundancy and recent advances in custom gene synthesis to produce recombinant full-length and glycosylated mucins on a large scale. We were able to successfully produce and purify recombinant synonymous lubricin (synLubricin) with lubricin’s native N- and C- terminal globular domains and a 59x consensus tandem repeat unit in its central domain. Building on the success of recombinantly producing fully-length lubricin, we developed various proof-of-concept glyco-engineered lubricin-inspired products for applications beyond biolubrication in PTOA. Additionally, we evaluated and optimized functional and pain-related assessments in the rat anterior cruciate ligament transection (ACLT) model of PTOA to improve the clinical relevance during our preliminary testing of synLubricin intra-articular therapy. Together, these findings enable further understanding of the role of lubricin in PTOA and provide valuable insight into therapeutic development of large mucin-like glycoproteins.