Polymer fiber-based models of connective tissue repair and healing

National Institutes of Health (R01-AR055280, Presidential Early Career Award for Scientists and Engineers, HHL)), the DoD CDMRP award (W81XWH-15-1-0685, HHL&WNL), and the Columbia University Center for Technology, Innovation and Communicty Engagement (CTICE Fellowship, NML)

Collagen Fibril Diameter Distribution of Sheep Anterior Cruciate Ligament

The anterior cruciate ligament (ACL) tissue is a soft tissue connecting the femur and tibia at the knee joint and demonstrates a limited capacity for self-regeneration due to its low vascularity. The currently available clinical procedures are unable to fully restore damaged ACL tissue, and tissue engineering can offer options with a potential of restoring the torn/ruptured ACL by using biomimetic constructs that are similar to native tissue in terms of structure, composition, and functions. However, a model substrate to understand how the ACL cells regenerate the injured tissue is still not available. In this study, it is hypothesized that the nanofiber-based model substrate with bimodal and unimodal fiber diameter distributions will mimic the diameter distribution of collagen fibrils seen in healthy and injured sheep ACL, respectively. The aims were to (i) create an ACL injury in a sheep ACL by applying extensional force to rupture the healthy ACL tissue, (ii) measure the collagen fibril diameter distributions of healthy and injured ACL, (iii) fabricate polycaprolactone (PCL) nanofiber-based model constructs using electrospinning with diameter distributions similar to healthy and injured ACL tissue, and (iv) measure mechanical properties of ACL tissue and PCL electrospun constructs. The results showed that the fiber diameter distributions of PCL electrospun constructs and those of the healthy and injured ACL tissues were similar. The novelty in this investigation is that the collagen fibril diameter distribution of healthy and injured sheep ACL tissues was reported for the first time. The study is significant because it aims to create a model construct to solve an important orthopedic-related clinical problem affecting millions of people globally. The model construct fabricated in this work is expected to have an important impact on ACL regeneration efforts

Effect of gadolinium concentration on temperature change under magnetic field.

Gadolinium based contrast agents (GBCAs) were found to play a role in nephrogenic systemic fibrosis in patients with and without renal impairment. Therefore, preserving the structural stability of GBCAs to reduce their propensity to liberate Gd3+ is of utmost importance. This study evaluates the effect of gadolinium concentration of GBCAs on solution temperature under magnetic fields. It is hypothesized that presence of gadolinium will lead to temperature changes of its solutions under magnetic field, and this change will depend on concentration. In this study, GBCAs were diluted to concentrations of 0.6, 1.2, 1.8, 2.4 mMol/L. A 10mL preparation in pure water, simulated body fluid (SBF), and plasma was scanned at 3T following a soft tissue neck protocol, and their temperatures were measured. Findings revealed that concentration of GBCA had significant effect on temperature change in all dilution media. Type of commercially available GBCA had an effect only in SFB and plasma. Evaluation of correlation between conditional stability constant (Kcond) and temperature difference (ΔT) revealed that in water and SBF there exists a positive correlation between Kcond and temperature variation. Collectively, GBCAs can cause local temperature variations when administered into patients, and can affect dissociation of gadolinium from its chelates, which should be investigated in a further study

CHANGE IN COLLAGEN FIBRIL DIAMETER DISTRIBUTION OF BOVINE ANTERIOR CRUCIATE LIGAMENT UPON INJURY CAN BE MIMICKED IN A NANOSTRUCTURED SCAFFOLD

More than 200,000 people are suffering from Anterior Cruciate Ligament (ACL) related injuries each year in the US. There is an unmet clinical demand for improving biological attachment between grafts and the host tissue in addition to providing mechanical support. For biological graft integration, it is important to provide a physiologically feasible environment for the host cells to enable them to perform their duties. However, behavior of cells during ACL healing and the mechanism of ACL healing is not fully understood partly due to the absence of appropriate environment to test cell behavior both in vitro and in vivo. This study aims at (i) investigating the change in fibril diameter of bovine ACL tissue upon injury and (ii) fabricating nanofiber-based scaffolds to represent the morphology and structure of healthy and injured ACL tissues. We hypothesized that distribution and mean diameter of ACL fibrils will be altered upon injury. Findings revealed that the collagen fibril diameter distribution of bovine ACL changed from bimodal to unimodal upon injury with subsequent decrease in mean diameter.....

A bioartificial rat heart tissue: Perfusion decellularization and characterization

Despite remarkable advancement in the past decades, heart-related defects are still prone to progress irreversibly and can eventually lead to heart failure. A personalized extracellular matrix-based bioartificial heart created by allografts/xenografts emerges as an alternative as it can retain the original three-dimensional architecture combined with a preserved natural heart extracellular matrix. This study aimed at developing a procedure for decellularizing heart tissue harvested from rats and evaluating decellularization efficiency in terms of residual nuclear content and structural properties. Tissue sections showed no or little visible cell nuclei in decellularized heart, whereas the native heart showed dense cellularity. In addition, there was no significant variation in the alignment of muscle fibers upon decellularization. Furthermore, no significant difference was detected between native and decellularized hearts in terms of fiber diameter. Our findings demonstrate that fiber alignment and diameter can serve as additional parameters in the characterization of biological heart scaffolds as these provide valuable input for evaluating structural preservation of decellularized heart. The bioartificial scaffold formed here can be functionalized with patient's own material and utilized in regenerative engineering