(489e) Conformationally Bioactive Bovine Serum Albumin As a Biomolecule in Tissue Engineering (Industry Candidate)

Serum albumin is one of the most abundant plasma proteins and has shown therapeutic potential in bone healing and regeneration. However, the biochemical mechanisms of activity are not well understood. Much of the evidence supporting albumin as beneficial to healing is seen in bone tissue, indicating that biomolecules or mineral ions enriched at healing sites could trigger the bioactivity of albumin. Additionally, we previously detected that bovine serum albumin (BSA) undergoes both an enhanced cell adhesive property and a conformational change when in the presence of calcium ions. The aim of this work is to better understand the biochemical mechanisms of albumin in bone healing and regeneration, as well as strategies for its incorporation into a tissue engineered scaffold.

In this study, we examined BSA bioactivity following adsorption onto TCPS after exposure to varying levels of calcium. The bioactivity was evaluated with respect to calcium exposure concentration, cell seeding density, initial cell attachment, cell viability, and integrin receptor activity. The most bioactive conformations were then covalently bound to a previously studied “blank-slate” polyampholyte hydrogel scaffold to isolate the biochemical impact of albumin while studying cell attachment and proliferation, for incorporation as a future tissue engineering platform.

We previously found that in the presence of calcium, BSA undergoes a conformational change as validated with both molecular modeling and FTIR. To investigate further, we explored osteoblast cell behavior based on varying calcium exposure levels. Cell attachment to BSA adsorbed on TCPS increases with the amount of calcium present, however, when the quantity of calcium gets too high, cell viability decreases rapidly. Cell attachment is partially reduced in the presence of an RGD peptide, but still exhibits high levels of cell attachment, so further integrin blockers were investigated to understand alternative integrin-mediated binding mechanisms. The trends seen on TCPS were validated on the “blank slate” polymer platform, representing a viable path forward for future clinical applications.

The bioactive conformation of BSA in the presence of calcium can facilitate enhanced bone repair through osteoblast cell adhesion and shows promise in aiding regeneration via a tissue engineered scaffold. Additional testing is in progress to isolate the specific bioactive peptide sequence in BSA.