Functional tissue engineering: Age-related changes and cell-based repair of the patellar tendon.

摘要

The objective of this study was to develop a mesenchymal stem cell (MSC) based therapy to repair a patellar tendon injury in the geriatric rabbit. We hypothesized that the biomechanics of normal and healing tendon would decline with increasing age and would require tissue engineering in order to withstand functional demands. We then hypothesized that an MSC-based therapy would not be as effective in the geriatric adult and would benefit from in vitro mechanical stimulation.; First, we found maximum stress in normal uninjured tendon declined 25% between 1 and 4 years of age and strain energy density declined 40%. These declines correlated with a reduction in collagen fibril diameter and an increase in type V collagen. In a later study using normal tendon as a control group, we were unable to support this claim as we found no age-related differences in biomechanics, but no biochemical measurements were made to ascertain a mechanism for the differences.; Next we found that repair tissue taken after creating a central-third patellar tendon injury in 1- and 4-year old rabbits was similar except at 26 weeks, where the maximum stress and modulus of the repairs from the 4-year old rabbits were significantly greater than repairs in the 1-year old rabbits.; We then demonstrated that autologous MSCs harvested from geriatric rabbits would repair patellar tendon defects as well as MSCs harvested from younger adult rabbits. Maximum stress and modulus for both groups were approximately 10.5MPa and 143MPa, respectively, which surprisingly, were lower than our values for natural healing. A subset of all rabbits developed ectopic bone in the repair region due the MSCs.; To attenuate ectopic bone formation and to encourage tenocyte differentiation, MSC-seeded collagen constructs were mechanically stimulated. No significant differences were observed between young or geriatric age groups or among continuous, intermittent, and unstretched constructs for biomechanics, collagen content, or collagen orientation. Stress relaxation during stretching may have been responsible for the lack of a positive effect.; Future studies are required to identify better models of aging, multiple biomarkers that measure the progression of age, and an improved mechanical stimulation system.