Even when viable cells are present, the newly synthesized matrix may not be sufficiently cross-linked to the native tissue. This study aims to overcome all of these factors by supplying viable cells to the interface via engineered neocartilage to mitigate the issues of cell death and lack of cell migration at the wound edge by exogenously inducing cross-links. One way to deliver cells at an interface may be via the use of constructs engineered using the self-assembling process, which is an established method for generating tissue with abundant cells at the construct edge. This method has also generated neocartilage with properties approaching those of native tissue. Maintenance of cartilage with normal functional properties requires sustaining cell density; large areas of cell death would undoubtedly result in biomechanically inferior matrix or none at all. Thus, this study seeks to use tissue engineered constructs created via chondrocyte self-assembly to deliver a higher cell density to the wound edge to enhance integration. Another suggested mechanism for the enhancement of integration is collagen pyridinoline cross-links. PYR crosslinks have been shown to be a major factor in determining the stiffness of connective tissues. PYR naturally forms within cartilage and other musculoskeletal tissues during development and aging via the enzyme lysyl oxidase, a metalloenzyme that converts amine side-chains of lysine and hydroxylysine into aldehydes. In vivo, LOX is most active at sites of growing collagen fibrils. A potential method for inducing collagen cross-linking across cartilage interfaces is thus the exogenous application of this enzyme. Since LOX is a small-sized molecule, at roughly,50 kDa, and since cross-link formation occurs over several weeks, exogenous LOX can be applied to in vitro cultures on a continuous basis to ensure full penetration via diffusion and to allow sufficient time for cross-link formation. By employing LOX, one would expect the formation of “anchoring” sites, composed of PYR cross-links in the collagen network of the engineered tissue as well as of the native tissue, to bridge the two tissues together. Thus, LOX application combined with the delivery of high cell numbers to the wound edge are expected to promote tissue integration. Using the self-assembling process, the objective of this study was to determine whether LOX can alter the integration of native-toconstruct and native-to-native tissue systems through two experiments. It was hypothesized that application of LOX would enhance integration, as evidenced through tensile measurements. The first experiment sought to examine whether LOX would promote integration between native cartilage and neocartilage and to determine time and duration of application. The second experiment sought to determine whether the results from the first experiment can be replicated in a native-to-native cartilage micrornas influence processes negative regulation binding targets system. Motivated by the as-of-yet unsolved issue of cartilage integration, the objective of this study was to examine the hypothesis that LOX would induce cartilage integration. This enzyme naturally occurs in cartilage and promotes PYR cross-links in collagen, thereby holding potential for strengthening cartilage-to-cartilage interfaces. The hypothesis was proven to be correct as evidenced by the biomechanical and histological data. At the dosage applied, this naturally occurring enzyme did not alter cellular response with respect to collagen and GAG production. Engineered tissues, formed using a self-assembling process, were integrated to native tissue explants by applying LOX to a ring-and-implant assembly. Additionally, LOX was applied to native-to-native cartilage interfaces to examine whether this novel integration method can also be applicable to cases where there is not an abundance of cells at the wound edge.