Proteoglycans (PGs) are a major building block and a hydrating agent in the extracellular matrix, which maintains structural organization of cells within tissues. PGs retain water and regulate flow of minerals and other nutrients, lubricate and provide mechanical support to the tissues. The combination of PGs and collagen forms the major structural component of cartilage. PGs degrade with aging and degeneration and weaken the tissues they support, resulting in wearing out of cartilage and ensuing arthritis, development of lower back pain and other progressive conditions. To slow the degradation of PGs and restore the function of the organs weakened by it, Drexel’s researchers have developed biomimetic proteoglycans (BPGs), a new injectable synthetic material mimicking naturally occurring PGs and capable of replacing them in the body.
Natural PGs are large macromolecules with a protein core and glycosaminoglycan (GAG) bristles. The largest of these is aggrecan resembling bottle brush architecture. Natural PGs are degraded in the body by various enzymes that attack their protein core. To prevent enzymatic degradation, BPGs use a synthetic polymer core instead of the protein core, but maintain naturally occurring GAG bristles. Thus, on the outside, the BPGs are indistinguishable from naturally occurring PGs, while the inside polymer core resists enzymatic degradation, making them better sustained in the body.
BPGs can be used in a variety of therapeutic and cosmetic applications. They can be delivered to the site of treatment via injection using a 33 gauge needle or applied topically. Due to their solubility BPGs penetrate extracellular matrix of tissues and integrate with collagen. The GAG bristles of BPG molecules are highly hydrophilic and negatively charged, leading to strong retention of water and electrostatic repulsion between BPG molecules. This allows BPGs to withstand significant pressure and maintain the bulk of their volume when compressed. These mechanical features enable a broad variety of healthcare applications of BPGs.
Market opportunity
Product applications of BPGs range from the treatments of lower back pain, arthritis and stress-induced urinary incontinence to tissue fillers and lotions.
Lower back pain. Annually, 15%-20% of the population experiences lower back pain; 60% or more will experience back pain over a lifetime. Epidural injections of steroids used for managing chronic back pain increased from 802,735 in 1998 to 1,776,153 in 2005 (121% over 7 years), as reported by Medicare. The same injection can be used to deliver BPGs into the nucleus pulposus to restore its normal mechanical properties by enabling the retention of water and the bulk of nucleus pulposus under pressure of the body weight, thus alleviating back pain for many months after a single injection. Such BPG injection could become an effective early-stage treatment of the degenerative disc disease.
Viscosupplementation. Rising prevalence of osteoarthritis (OA) and patients seeking to delay knee replacement surgery are the key drivers in the viscosupplements market of about $900M in 2016 and projected to grow to $1.4B by 2023 in the US alone. Drexel’s BPG have been tested in a rabbit model of OA and demonstrated rapid incorporation into the knee cartilage, positioning them as a potential future leader in the market of minimally invasive treatments for arthritis.
Stress-induced urinary incontinence and tissue fillers. BPGs’ propensity for retaining water and volume under stressful conditions makes them ideal candidates for use as bulking agents and tissue fillers. Drexel PGB injections in rabbit models have verified desired BPG distribution within the urethral tissue with the ability to modulate mechanical behavior of the tissue. They have also been injected in the mid-dermis to achieve lasting tissue bulking/filling effects. These markets represent a several billion dollar opportunity each.
Moisturizers. Due to their superior water retention properties BPG added to lotions can be highly effective moisturizers, which represent about a $20B market.