Rice University bioengineering graduate students Brandon Smith and Emma Watson have each been selected for a Ruth L. Kirschstein National Research Service Award (NRSA) by the National Institutes of Health to develop new biomaterials and carriers for drug delivery that promote craniofacial bone and soft tissue regrowth with reduced risk of infection.
NRSA fellows are selected after rigorous peer-review and scoring of the proposed work by a panel of established and senior scientists. Awardees are provided up to five years of predoctoral support at various stages of education and training.
Both Smith and Watson conduct research in Antonios Mikos’ laboratory at Rice’s BioScience Research Collaborative (BRC) and are M.D./ Ph.D. students in the Medical Scientist Training Program (MSTP) run jointly by Rice and Baylor College of Medicine (BCM). Mikos, who is their primary adviser, is Rice’s Louis Calder Professor of Bioengineering and Chemical and Biomolecular Engineering.
Synthetic bone substitutes, such as calcium phosphate cements (CPC), have shown great promise for the regeneration of bone. Smith will use his NRSA fellowship to incorporate biocompatible, glucose-based microparticles into the CPC to significantly increase the scaffold’s interconnected pore structure and allow for rapid nutrient and antibiotic delivery. The work builds from previous research in collaboration with John Jansen, a professor in biomaterials at Radboud University Nijmegen.
Smith says CPCs can be readily injected and adapted to the shape of the defective site. “The challenge we face is the scaffold’s slow degradation rate, which hinders the ability for native tissue ingrowth. Outcomes from this project will provide insight into how glucose-based microparticles can be used in new tissue engineering and therapeutic approaches for complex bone defects of large or unusual sizes.”
Smith, a native Houstonian, is in his fourth year of studies at Rice. After completing his Ph.D., he will complete the clinical curriculum at BCM. His long-term goal is to become a physician scientist in the field of orthopedic surgery. He has a B.S. in chemical engineering from University of Oklahoma.
The focus of Watson’s NRSA fellowship is to manufacture and test porous polymethylmethacrylate (PMMA) implants, which serve as a space holder in craniofacial reconstruction and deliver controlled release of antibiotics. Her clinical adviser is Mark Wong, an oral and maxillofacial surgeon at the University of Texas Health Science Center at Houston (UTHealth) School of Dentistry.
The lab’s specialized PMMA implants are designed to keep a pocket for new bone open while the overlying soft tissue heals. The space maintainers are created using 3-D printed molds allowing for the creation of patient-specific devices. In later surgery, the implant is removed to make way for reconstruction of the bone using transplanted bone harvested from the patient's own body.
“The novelty of our approach is that we leverage bone tissue’s ability to repair itself and grow tissue in vivo,” explained Watson. “Using the patient’s own cells, new bone is cultured for up to three months to match the shape of bone we are replacing in a customized chamber that is implanted in an isolated area, such as in rib periosteum.”
Jawbone defects are susceptible to invasion by bacteria as a result of trauma, or disease, and through local soft tissues, such as nasal passages, the sinuses and the mouth. Watson said her NRSA research will also involve, “the evaluation of space maintainers and the interplay between bacteria, antibiotic delivery, and the body’s immune response to bone growth, which will provide us with the information we need for tighter control of antibiotic release.”
Watson is in her third year of doctoral studies at Rice. She was born near Belfast, Northern Ireland, and became a U.S. citizen this year. She has a B.S. in chemical engineering from the University of Kansas. After completing the Rice-BCM physician scientist program, she will apply to residency programs, likely in the field of otolaryngology and head and neck surgery.
Mikos is also director of the J.W. Cox Laboratory for Biomedical Engineering, and director of two BRC-based centers – the Center for Engineering Complex Tissues and the Center for Excellence in Tissue Engineering. His lab specializes in the development of new biomaterials for use as scaffolds for tissue engineering, as nonviral vectors for gene therapy and as carriers for controlled drug delivery.
Since 2008, the lab has actively collaborated with physicians and scientists at UTHealth, Wake Forest Institute for Regenerative Medicine, and the U.S. Army Medical Research and Material Command through the Armed Forces Institute of Regenerative Medicine (AFIRM) grants to speed the availability of replacement tissue and organs to patients.