The long term goal of this project is to advance the modern management of traumatic brain injury (TBI) by performing a single-stage decompressive craniectomy procedure. To accomplish this goal, we propose utilizing bone regenerative medicine and the development of novel bone paste. A novel biomaterial such as we propose will have several benefits: (1) It can be applied at the time of the initial TBI procedure, thus preventing a second cranioplasty procedure to restore the missing skull, (2) it will be temporarily pliable and allow brain swelling and decompression as is physiologically necessary immediately after TBI, (3) as brain swelling resides it will contract and be osteoconductive/osteoinductive promoting natural cranial bone reformation, (4) it will prevent known long- term neurologic deficits associated after craniectomy termed ?syndrome of the trephined?. Decompressive craniectomy is a common life-saving neurosurgical procedure utilized to treat TBI in patients with either closed head injury and/or brain ischemia/stroke. By removing half of the calvarial bone, the brain is ?decompressed? by allowing it to swell beyond the confines of the cranial vault, thus mitigating rising intracranial pressures and preventing cortical injury. As the brain swelling subsides, the unprotected cerebral hemisphere begins to sink beyond its native cranial dimensions, causing neurologic deficits, termed ?syndrome of the trephined.? Symptoms include headaches, depression, and loss of fine motor coordination. These symptoms and deficits are reversible but they require a second-stage cranioplasty procedure to restore the cranial anatomy as treatment. The primary objective of this project is to establish a single-surgery decompressive craniectomy procedure using a novel biomaterial. The chief hypothesis is that application of a novel paste-like natural biomaterial immediately following TBI and craniectomy will not only regenerate the cranial bone without the need for a second procedure, but will prevent the neurological deficits associated with syndrome of the trephined. To test this hypothesis, we propose the following aims: 1) Characterize a rat model of TBI with motor deficits attributed to hemi-craniectomy and 2) Implant a paste-like material immediately following hemi-craniectomy to evaluate bone regeneration and alleviation of neurological symptoms. With expertise in bone regeneration, biomaterials, craniofacial surgery and TBI treatment/animal studies, and clinical translation of technology, our team is uniquely qualified to complete this project. Successful implementation of this technology will advance the treatment of TBI.

Public Health Relevance

We propose to revolutionize traumatic brain injury (TBI) treatment by utilizing a regenerative bone paste which allows a surgeon to perform a single-stage operation that improves neurorehabilitation and health. Currently, TBI patients are treated by removing a large amount of skull allowing brain decompression; leaving the patient with a permanent skull defect that causes neurologic deficits termed syndrome of the trephined and requires a second-stage operation to treat. Our regenerative bone paste will be placed at the time of brain decompression, will allow brain herniation, and will regenerate bone as the brain swelling subsides, eliminating the need for the second operation thus preventing neurologic deficits of syndrome of the trephined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
1R03DE025906-01A1
Application #
9245216
Study Section
NIDR Special Grants Review Committee (DSR)
Program Officer
Lumelsky, Nadya L
Project Start
2017-02-01
Project End
2019-01-31
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Kansas
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160