Development as a New Paradigm for Improved Tendon Healing: A Characterization of Neonatal Tendon Development, Healing During Development and an Investigation Into Differential Parameters During Accelerated Healing

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URL: https://repository.upenn.edu/edissertations/1565

PROQUEST: 858204588

Abstract

During neonatal development, tendons undergo a well orchestrated process whereby extensive structural and compositional changes occur in synchrony to produce a normal tissue. Conversely, during the repair response to injury, structural and compositional changes occur, but in this case, a mechanically inferior tendon is produced. An injured tendon that is mechanically inferior has compromised function and reruptures after treatment are commonly observed clinically. As a result, the process of development has been postulated as a potential paradigm through which improved adult tissue healing may occur. First, the role of CD44 in healing was examined through a patellar tendon injury in a CD44 knockout mouse. A beneficial environment post injury was shown to lead to improved function in the CD44 knockout tendons. Second, type XIV collagen was examined in tendons during development and maturity through Col14a1-/-, Col14+/- and Col14+/+ flexor digitorum longus tendons. A lack of type XIV collagen during development was associated with reduced mechanical parameters but had no effect in mature tendons. Third, compositional, structural and mechanical properties were quantitatively characterized during multiple stages of neonatal Achilles tendon development in a mouse. Mechanical parameters, collagen content, fibril diameter average and standard deviation all increased with age. Biglycan expression decreased with age while decorin and angular deviation did not change. Fourth, compositional, structural and mechanical parameters were quantified after injury during two different stages of development, early and late. An accelerated healing process was demonstrated during early development over late development. Lastly, regression analysis was used to determine which compositional and structural parameters predicted mechanical parameters during early and late development and healing. Applying these differentially regulated parameters to new treatments may help improve healing in adult tendons. Importantly, this dissertation was conducted in a mouse model which is allows for future mechanistic studies due to the availability of genetically modified mice and commercially available assays. Over all, this dissertation introduces development as a new paradigm through which to study improved function during healing and potential new therapeutic treatments.

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