Tendons transduce force from muscle to bone and enable locomotion of the body. They are comprised mainly of collagen-1, glycoproteins, and proteoglycans which make up a highly aligned and hierarchical extracellular matrix (ECM) which can withstand the high loads necessary for its day-to-day function. This ECM is maintained, healed, and adapted in response to loading by resident tenocytes which reside between collagen fibers. Upon acute injury, the ECM alignment is disrupted, and adult mammalian tendons do not have an innate ability to heal these injuries, leading to formation of scar tissue. Current therapeutics are for symptom management – such as NSAIDs, physical therapy, and pain medication – rather than addressing the underlying scar formation. Because the underlying scar is never addressed, retear rates after tendon reattachment surgery are frequently over 50%. The MRL/MpJ (MRL) mouse is a model of scarless tendon healing. Previous members of my lab have shown that the local MRL tendon healing environment not only drives its own healing capacity, but can drive healing when added exogenously (as “M7”) to scar-mediated healers such as the C57Bl/6 (B6) mouse. We identified 29 proteins (POIs) that were particularly enriched in the MRL healing environment compared to the nonhealing B6. The goal of this thesis is to establish the capacity of these 29 POIs to improve tendon functional outcomes in midsubstance punched B6 patellar tendons, and what mechanism drives this adult mammalian scarless tendon healing. To accomplish this goal, this thesis will be broken down into two major objectives. Objective 1 (Chapter 2) uses a series of in vivo studies to evaluate the temporal and dose windows in which the POI therapeutic can be used to functionally restore tendons. Further, I develop an alternative route of delivery in the form of a PEG-4MAL gel for future translational application. Given the success of the POIs to mechanically restore the mechanics of B6 patellar tendons after midsubstance punch, the second objective (Chapter 3) was to evaluate the mechanism behind this scarless healing. Transcriptomics informed pathway enrichment and upstream regulator identification was paired with proteomic biological process enrichment to identify two biological drivers that are shared between MRL and B6+POI treated tendons compared to B6 tendons. Together, this work provides a recombinant protein therapeutic for scarless healing and a proposed mechanism of action for this improved healing cascade. This is groundbreaking for developing translatable tendon therapeutics that can be used clinically.