Craniosynostosis is a condition in which one or more cranial sutures closes prematurely and occurs in approximately 1 of every 2000 live births. If left untreated, craniosynostosis can result in blindness, deafness, developmental delays and death. Treatment includes removal of the suture but there can be up to 40% chance of re-synostosis, especially in patients under six months. This necessitates additional surgical intervention which is associated with up to a 13% risk of life threatening complications. Although recent advances have been made in understanding the genetic and molecular mechanisms involved in regulating suture fusion, there are no effective clinical therapies available to treat craniosynostosis other than complete calvarial reconstruction and there are no therapies for re-synostosis.
The hydrogel device is designed to delay regrowth of bone in the suture following surgical intervention for craniosynostosis. The device is an injectable hydrogel that spontaneously polymerizes in situ and can be used at the time of the original surgery or delivered percutaneously after surgery. Our system is a pair of mutually reactive liquids (like an epoxy adhesive) that rapidly (<90 sec) react using “click chemistry” to form a gel. Toxicity is reduced or eliminated because no chemical or ultraviolet light initiator is needed. Rapid formation (far faster than other known click hydrogels) is a key enabling feature for delivery by injection to specific sites. Thus, our hydrogels are ideal platforms for use in children given their ability to conform to the shape of tissue defects without eliciting local or systemic toxicity.
The hydrogel system will provide a dramatic reduction in the invasiveness of the surgical procedure, eliminating the need for blood transfusions and lengthy stays in the hospital. Another dramatic impact would be the ability to treat this condition at a much earlier age, before many of the skull deformities occur. Thus, the operation can be completed safely at a very early age and prevent as opposed to correct skull deformities.
This project was originally funded by the Atlanta Pediatric Device Consortium. The consortium provided advice to leverage our grant by applying to other grants. The consortium sponsors facilitated the discussions with the FDA concerning the classification of our device. When the project joined the consortium the device was in the prototyping stage of development. To test effectiveness of the click hydrogel system, we developed a rat cranial defect model that mimics craniosynostosis, a condition in children where the sutures in the skull fuse prematurely. Surgical defects heal rapidly in weanling mice but fail to heal with bone in adolescent animals. From a product development perspective, the skull is easy to access and monitor by microCT and histology, and there is a favorable regulatory pathway through the FDA Office of Orphan Products Development for pediatric rare diseases. By itself, the hydrogel delays resynostosis in weanling mice and as a result, the FDA Office of Product Designation defined it to be a device with regulatory authority in the Center for Device and Radiologic Health (CDRH). We have performed a series of in vitro toxicity studies required by FDA, but we need to complete these experiments and test toxicity in vivo.
Based on our findings, we were able to successfully compete for funds from the Department of Defense, which were used to investigate whether the device could be used to treat cranial defects that were not suture-associated but resulted from cranial reconstruction procedures. Most recently, we received funding from Virginia’s Commonwealth Research Commercialization Fund (CRCF), which will be used to perform critical preclinical animal studies using the hydrogel formulations that are established in our APDC-funded toxicity tests. The data resulting from the current APDC grant are important for demonstrating potential for commercialization by establishing safety of the device.