Biomimetic Proteoglycans

Biomimetic Proteoglycans

Lower back pain has been estimated to be the fifth most common reason for all physician visits and is the leading musculoskeletal disease confronting out healthcare system. Lower back pain can be attributed to the process of intervertebral disc (IVD) degeneration where the proteoglycan content of the nucleus pulpous decreases linearly with degeneration. These proteoglycans are essential for the hydration and structural integrity of soft and connective tissue. Proteoglycans such as aggrecan work to resist mechanical forces and provide hydrostatic tension to the outer region of the intervertebral disc. As the soft and connective tissues degenerate, enzymatic degradation of proteoglycans outpaces cellular synthesis which leads to hydration, mechanical,  and nutritional deficits to tissue function. Due to the cost prohibitive nature of proteoglycan restoration with natural molecules, we are currently working to synthesize cytocompatible biomimetic proteoglycans (BPGs) to mimic the size and three-dimensional bottle brush  architecture of their natural counterparts with an ultimate goal of creating potential BPGs for the purpose of molecular engineering of degenerated tissue.

Blastocyst Adhesion

Blastocyst Adhesion

Infertility remains a great challenge to reproductive biology in today’s world.  One of the critical steps in the reproductive process is the embryo implantation; an inability of the blastocyst to attach to the epithelial wall of the human endometrium is a leading cause of both natural and in vitro infertilization.  In in vitro fertilization, this is the principle cause of the 70% failure rate of successful embryo transfers.  This attachment of the blastocyst to the endometrium is initially mediated in part by an L-selectin adhesion system.  This system consists of L-selectin on the trophoblasts, or exterior cells of the blastocyst, attaching to oligosaccharide ligands on the surface of the endometrium.  This adhesion system is weak however, and is followed by a secondary integrin-ligand interaction. In the lab we are working to understand the mechanisms of both the primary and secondary attachment system.  Currently, we are quantifying the bond strength of L-selectin to its ligands by applying shear forces due to fluid motion through a custom-build Parallel Plate Flow Chamber and determining the detachment strength of these bonds.

Intervertebral Disc High Impact Loading

Naval Special Warfare (NSW) personnel are exposed to repeated shocks during operation of their high-speed boats. The shocks stem from the changing vertical accelerations that lead to the upward pitching and then downward crashing of the vehicle in open water missions. Over time, this repeated loading results in back pain and intervertebral disc degeneration for the personnel. Unfortunately, due to the lack of detailed information regarding the subject, the relationships between high impact loads and disc biomechanics is not well understood. Due to this, we are currently working to obtain more information on disc biomechanics and high impact loading in an effort refine ISO Standards to better reflect conditions of special operations units serving on high-speed boats. The main goal of this project is to obtain data on the mechanical behavior and failure analysis of intervertebral discs subjected to high impact loading scenarios.

Disc Herniation

The vertebrae of your spine are separated from one another by pads of cartilage called Intervertebral discs (IVDs). The discs cushion against the shocks and strains experienced as you move and put various stresses on your spine. The discs are subject to injury, disease, and degeneration with use over time. When the interior material of a disc called the nucleus pulopsus (NP) pushes out through a tear or weakening in the outer covering called the annulus fibrosus (AF), the disc is said to be herniated. There are 3 main types of disc injuries. The first disc injury consists of annular fiber tears which do not extend to the outer aspects of the disc. The inner NP does not completely leave the disc.  The second type of disc injury is a disc herniation.  A disc herniation consists of annular tears which run through the AF. The pressurized NP material can squeeze through the tears in the annulus and escape to the outside of the disc. When this occurs, the NP material may come in contact with nearby spinal nerves and even the spinal cord.  In the third type of disc injury, referred to as a disc bulge, the inner nucleus loses hydration; common in those with prolonged spinal stress and the elderly. This results in “bulging” of the disc. Similar to the previous injury, the nearby spinal nerves and spinal cord may become impinged from the bulging disc. Using mechanical testing experiments and analysis we are developing fracture and fatigue techniques for the AF of the IVD. Through this, the goal is to be able to predict crack propagation in the disc (annular tears) which ultimately leads to disc herniation.

Injectable Polyurethane for Vertebroplasty and Kyphoplasty

Compression fractures can be caused by various conditions, including osteoporosis and tumors. Vertebroplasty and Kyphoplasty are minimally invasive surgical procedures that attempt to relieve the pain, loss of height, and hunched or stooped posture induced by vertebral compression fractures.  Both procedures use bone cement to stabilize the bone affected by the fracture.  Currently, PMMA is used in both Vertebroplasty and Kyphoplasty.  Although approved by the FDA, it is not ideal for these procedures.  The exothermic polymerization of PMMA can cause thermal necrosis of neural tissue. PMMA also has a significantly higher elastic modulus than that of trabecular bone, which may lead to fractures in adjacent vertebrae. PU was examined as a potential material for use in Vertebroplasty and Kyphoplasty. PU consists of a hard segment and a soft segment.  MDI was chosen as the hard segment due to its ability to provide higher siffness, mechanical strength, and modulus to the polymer. The soft segment, PTMO, is ideal because itprovides flexibility and softness.  It is our aim to create an injectable PU cement with an elastic modulus closer to that of trabecular bone, and thereby provide an alternative to PMMA for Vertebroplasty and Kyphoplasty procedures.

Periprosthetic Infection

Infection is a serious complication of implantable medical devices, including orthopedic implants fabricated from PEEK (Polyetheretherketone) and PEEK composites, which are increasingly being used for more spinal and orthopaedic devices. Attempts at different methods to modify PEEK to create an infection resistant material are being performed.  First, using silver composities of PEEK because silver ions are active against a wide range of bacteria and fungi and have a low-propensity for bacteria to develop a resistance.  We will try to discover and optimize the best method to reduce or irradicate bacterial attachment and biofilm development on PEEK surfaces. We are trying to develop the Drexel processing facilities to mold and analysis PEEK more efficiently and accurately.  Recently a method to characterize crystallinity levels in PEEK using specular reflectance FTIR has been developed, which has become and ASTM standard.