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Maturation state-dependent alterations in meniscus integration: implications for scaffold design and tissue
Lara C Ionescu1, Gregory C Lee, Grant H Garcia
1McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Insights
As knee meniscus tissue matures, its natural healing ability declines due to changes in tissue composition. Growth factors like TGF-β3 can enhance healing in adult meniscus, aiding tissue engineering.
Area of Science:
- Biomaterials Science
- Orthopedic Research
- Developmental Biology
Background:
- The knee meniscus is vital for joint stability and load distribution.
- Meniscus tears are common, with limited natural healing capacity.
- Fibrocartilaginous tissues show regenerative potential in immature subjects.
Purpose of the Study:
- To investigate the age-related changes in bovine meniscus properties and in vitro repair capacity.
- To assess the impact of maturation on meniscus healing potential.
- To evaluate the efficacy of transforming growth factor-beta 3 (TGF-β3) and engineered scaffolds in promoting meniscus integration.
Main Methods:
- Comparative analysis of fetal, juvenile, and adult bovine meniscus.
- In vitro assessment of cell behavior (migration, proliferation).
- Histological and mechanical evaluation of tissue repair and cellular infiltration into nanofibrous scaffolds.
Main Results:
- Significant changes in proteoglycan, collagen, and DNA density/distribution with age.
- Decreased in vitro healing capacity in adult meniscus compared to fetal and juvenile.
- Enhanced integration of adult meniscus with TGF-β3; improved scaffold integration observed.
Conclusions:
- Maturation-induced changes for load-bearing compromise endogenous healing potential in adult meniscus.
- Age-related decline in meniscus repair capacity is a critical factor for tissue engineering.
- TGF-β3 and novel scaffold designs show promise for improving meniscus regeneration.
Abstract:
The knee meniscus is a crucial component of the knee that functions to stabilize the joint, distribute load, and maintain congruency. Meniscus tears and degeneration are common, and natural healing is limited. Notably, few children present with meniscus injuries and other related fibrocartilaginous tissues heal regeneratively in immature animals and in the fetus. In this work, we evaluated fetal, juvenile, and adult bovine meniscus properties and repair capacity in vitro. Although no changes in cell behavior (migration and proliferation) were noted with age, drastic alterations in the density and distribution of the major components of meniscus tissue (proteoglycan, collagen, and DNA) occurred with development. Coincident with these marked tissue changes, the in vitro healing capacity of the tissue decreased with age. Fetal and juvenile meniscus formed a robust repair over 8 weeks on both a histological and mechanical basis, despite a lack of vascular supply. In contrast, adult meniscus did not integrate over this period. However, integration was improved significantly with the addition of the growth factor transforming growth factor-beta 3. Finally, to evaluate engineered scaffold integration in the context of aging, we monitored cellular infiltration from native tissue into engineered nanofibrous constructs. Our findings suggest that maturation processes that enable load bearing in the adult limit endogenous healing potential and identify new metrics for the development of tissue-engineered meniscus implants.
