MSE Seminar: “Biomolecule/Cell Interactions with Biomaterials and Bone Biomineralization”

Details

Nita Sahai, Ph.D.
Professor, Department of Polymer Science
University of Akron

Abstract:

My research focuses on understanding the interactions of cells or biomolecules with minerals relevant to orthopaedic biomaterials, bone biomineralization and antimicrobial materials. Our group’s approach is to use combine experimental methods molecular dynamics simulations to gain insight into the key molecular and nanoscale mechanisms. I will present on three study areas: (1) in orthpaedic biomaterials research, we have explored various aspects of silica as an osteoinductive factor. We showed that the crystal structure of calcium silicate polymorphs (a-CaSiO3 vs. b-CaSiO3) control their rate of resorption, which in turn controls calcium and silicate ion release (osteoinductive ions), thus controlling the extent of osteogenic stem cell differentiation on the two polymorphs. Furthermore, it was known for the last 40 years that silicate from dietary as well as silicate biomaterials promotes bone growth but the biological mechanism remained unclear. We showed recently that dissolved silicic acid (Si(OH)4) decreases TNFα-induced activation of NF-κB, a signal transduction pathway that inhibits osteoblastic bone formation, through the known miR-146a negative feedback loop. Thus, we established a mechanism for silicic acid to promote osteogenesis by antagonizing NF-κB activation via miR-146a. (2) Bone is a hierarchical, nanocomposite material whose mechanical properties depend partly on the size, shape and alignment of hydroxyapatite nanocrystals associated with a collagenous matrix. Our studies have revealed the potential mechanisms of collagen mineralization and hydroxyapatite nanocrystal growth modulation, which should help design improved scaffolds for bone tissue engineering. (3) Finally, my colleague Dr. Abraham Joy’s group has developed peptidomimetic antimicrobial polyurethanes with broad spectrum antimicrobial activity. We have collaborated with the Joy group to reveal a relationship between side chain identify and the specific peptidomimetic polyurethanes ability to kill Gram negative or Gram positive bacteria.
I will present on three study areas: (1) in orthpaedic biomaterials research, we have explored various aspects of silica as an osteoinductive factor. We showed that the crystal structure of calcium silicate polymorphs (a-CaSiO3 vs. b-CaSiO3) control their rate of resorption, which in turn controls calcium and silicate ion release (osteoinductive ions), thus controlling the extent of osteogenic stem cell differentiation on the two polymorphs. Furthermore, it was known for the last 40 years that silicate from dietary as well as silicate biomaterials promotes bone growth but the biological mechanism remained unclear. We showed recently that dissolved silicic acid (Si(OH)4) decreases TNFα-induced activation of NF-κB, a signal transduction pathway that inhibits osteoblastic bone formation, through the known miR-146a negative feedback loop. Thus, we established a mechanism for silicic acid to promote osteogenesis by antagonizing NF-κB activation via miR-146a.

(2) Bone is a hierarchical, nanocomposite material whose mechanical properties depend partly on the size, shape and alignment of hydroxyapatite nanocrystals associated with a collagenous matrix. Our studies have revealed the potential mechanisms of collagen mineralization and hydroxyapatite nanocrystal growth modulation, which should help design improved scaffolds for bone tissue engineering.

(3) Finally, my colleague Dr. Abraham Joy’s group has developed peptidomimetic antimicrobial polyurethanes with broad spectrum antimicrobial activity. We have collaborated with the Joy group to reveal a relationship between side chain identify and the specific peptidomimetic polyurethanes ability to kill Gram negative or Gram positive bacteria.