A rabbit antiserum (anti-EP), induced against a synthetic peptide corresponding to residues 68 to 86 of guinea pig myelin basic protein, powerfully immunostained abnormal-appearing oligodendrocytic processes and cell bodies in demyelinating areas associated with multiple system atrophy (MSA). However, as we reported previously, the antiserum, which is highly specific for the sequence QDENPVV corresponding to human myelin basic protein residues 82 to 88, failed to recognize any structures in normal human brain. QD-9, a mouse monoclonal antibody raised against human myelin basic protein residues 69 to 88, which also recognizes specifically the epitope QDENPVV, gave the same results as did anti-EP. The unusual epitope recognized by anti-EP/QD-9 antibodies appears to be accessible in areas of myelin degeneration, and the antibodies have been shown to detect such areas in multiple sclerosis and infarcted brains. These antibodies detect myelin degeneration more widely than previous conventional methods. The present study emphasizes the importance of myelin degeneration in the pathogenesis of multiple system atrophy.

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.

Aligned nanofibrous scaffolds can recapitulate the structural hierarchy of fiber-reinforced tissues of the musculoskeletal system. While these electrospun fibrous scaffolds provide physical cues that can direct tissue formation when seeded with cells, the ability to chemically guide a population of cells, without disrupting scaffold mechanical properties, would improve the maturation of such constructs and add additional functionality to the system both in vitro and in vivo. In this study, we developed a fabrication technique to entrap drug-delivering microspheres within nanofibrous scaffolds. We hypothesized that entrapping microspheres between fibers would have a less adverse impact on mechanical properties than placing microspheres within the fibers themselves, and that the composite would exhibit sustained release of multiple model compounds. Our results show that microspheres ranging from 10~20 microns in diameter could be electrospun in a dose-dependent manner to form nanofibrous composites. When delivered in a sacrificial PEO fiber population, microspheres remained securely entrapped between slow-degrading PCL fibers after removal of the sacrificial delivery component. Stiffness and modulus of the composite decreased with increasing microsphere density for composites in which microspheres were entrapped within each fiber, while stiffness did not change when microspheres were entrapped between fibers. The release profiles of the composite structures were similar to free microspheres, with an initial burst release followed by a sustained release of the model molecules over 4 weeks. Further, multiple model molecules were released from a single scaffold composite, demonstrating the capacity for multi-factor controlled release ideal for complex growth factor delivery from these structures.

No abstract

Meniscal surgeries are amongst the most common procedures performed in orthopedics today. Clinical solutions are few and have limited success, and so partial meniscectomy is a common outcome. While tears are common in older patients, few young patients present with meniscus damage. It is unclear whether juvenile menisci are less susceptible to damage or more given to endogenous repair. Early in development, the menisci are well vascularized throughout their radial expanse, while in adults, vascularity is restricted to the peripheral rim of the tissue, near the synovial margin [1]. Tears in this vascular region often do heal in adults, while those in the avascular inner regions of the tissue do not [2]. This has led to the inference that vascularity is essential for meniscus healing and this manner of thinking has directed numerous repair strategies toward that end [3].