A New Approach to Regenerative Cartilage Tissue Engineering Using Smart-Sensitive Nutraceutical Hydrogels

Injury and diseases that affect articular cartilage present a daunting challenge in orthopedic medicine. During the onset of injury or disease, low oxygen environments decrease healthy cartilage cell growth by limiting extracellular matrix production and creating reactive oxygen species (ROS) such as nitric oxide (NO). Ultimately, this environment reduces the efficacy of traditional biomaterials to cultivate a regenerative scaffold. Our research group has developed a therapeutic injectable hydrogel that provides a regenerative interface for cartilage tissue engineering via a cell-protective mechanism. Using Poly(N-vinylcaprolactam)[PVCL] a smart biomaterial that changes its molecular orientation upon temperature change along with its mechanical properties in conjunction with other natural therapeutic molecules. The hydrogel composite, containing PVCL-hyaluronic acid-NUTR (PVCL-HA-NUTR) affords a robust hydrogel with tunable (lower critical solution temperature) [LCST] parameters near physiological temperature. Our hydrogels have been investigated in vitrostatic cell culture and in vivostudies. Using 3D printing, hydrogels were also fabricated to compare the effect of material properties on cell proliferation and metabolism on extra cellular matrix (ECM) proteins. Fetal bovine chondrocytes were harvested and seeded [or 3D bioprinted] into various formulations of PVCL-HA-NUTR under normoxia (21%) and hypoxia (1%) low oxygen conditions. Our results show that chondrocyte cell viability at 1% O₂levels remained higher than that of 20% O₂levels in PVCL-HA for each time point. Animal studies were performed for 30 days after injection of therapeutic hydrogels into the defective knee joint confirm higher amounts of chondrocyte cloning within the murine joint. This work shows promise in providing a cyto-protective biomaterial construct that will begin to regenerate diseased articular cartilage.