Polymeric biomaterials for intervertebral disc repair (ISMMS)
Partnered with Dr. James Iatridis, a Professor of Orthopedics and Neurology at ISMMS on the following projects:
Controlled release of microparticles from spinal bioadhesives for intervertebral disc (IVD) degeneration
The goal of this project is to encapsulate a particular type of extracellular vesicle, called an exosome, into polymer microparticles. Exosomes are known to promote wound healing and make an attractive biologic drug compound. Dr. Iatridis has created a hydrogel that polymerizes in situ in the damaged IVD during surgery. However, the harsh polymerization reagents may damage the exosomes. The goal is to protect the exosomes and allow them to release over time from the hydrogel system. The exosomes are encapsulated into poly(lactic-co-glycolic acid) (PLGA) microparticles that are incorporated into the in situ hydrogel sealant during spinal surgery. The work involves developing protocols for the encapsulation, characterizing the microparticles, study their impact on the mechanics of the hydrogel, and studying the controlled release of the exosomes.
Cell delivery for intervertebral disc repair
The goal of the project is to evaluate the performance of fibrin-based hydrogels to enable cell delivery to heal the IVD space after herniation surgery. The project includes refining and analyzing ongoing work on a tissue engineering project for the annulus fibrosus to repair injured intervertebral disc (IVD) and prevent degeneration. The fibrin-based hydrogels are designed to carry cells encapsulated in cross-linked oxidized alginate. As the oxidized alginate degrades, the cells release and the void space left behind in the fibrin-based hydrogel allows room for proper extracellular matrices to form and support normal cell function. The work entails studying the biomechanical and biological analyses of cell-laden and cell-free hydrogels. A particular focus is on biomechanical performance and degradation of acellular hydrogels vs cellular hydrogels. The best formulations were then run in a custom ex vivo bioreactor to test the repair strategy over several months within live bovine IVDs.
Publications
- DiStefano, T. J., Chionuma, H. N., Danias, G., Vaso, K., Weiser, J. R., Iatridis, J. C., “Extracellular Vesicles as an Emerging Therapeutic for Intervertebral Disc Degeneration: Therapeutic Potential and Translational Pathways”Advanced Healthcare Materials 2021 Jul 23:e2100596. doi: 10.1002/adhm.202100596
- Panebianco, C.J., Rao, S., Hom, W.W., Meyers, J.H., Lim, T.Y., Laudier, D.M., Hecht, A.C., Weir, M.D., Weiser, J.R., Iatridis, J.C., "Genipin-Crosslinked Fibrin Seeded with Oxidized Alginate Microbeads as a Novel Composite Biomaterial Strategy for Intervertebral Disc Cell Therapy" Biomaterials 2022 June. doi: 10.1016/j.biomaterials.2022.121641
- DiStefano, T.J., Vaso, K., Panebianco, C.J., Danias, G., Chionuma, H.N., Kunnath, K., Karoulias, S.Z., Wang, M., Xu, P., Davé, R.N., Sahoo, S., Weiser, J.R., Iatridis, J.C., “Hydrogel-embedded Poly(lactic-co-glycolic acid) Microspheres for the Delivery of hMSC-derived Exosomes to Promote Bioactive Annulus Fibrosus Repair” CARTILAGE 2022 July. doi: 10.1177/19476035221113959
Theses
- Thesis abstract – Keti Vaso – “Evaluation of the Regenerative Potential of Mesenchymal Stem Cell-derived Exosomes for Annulus Fibrosus Repair and Controlled Delivery Using Hydrogel-embedded Poly(lactic-co-glycolic acid) Microspheres”
Conferences
- Conference Proceeding – AIChE 2020 – Keti Vaso (presenter), et al. – “Sonication-free Fabrication and Characterization of Hydrogel-embedded Poly(lactic-co-glycolic acid) Microspheres for Extracellular Vesicle Delivery to the Intervertebral Disc”
- Conference Proceeding – 9th Annual Musculoskeletal Repair and Regeneration Symposium – Christopher Panebianco (presenter), Sanjna Rao – “Seeding Oxidized Alginate Microbeads within Genipin-Crosslinked Fibrin Hydrogels for Intervertebral Disc Repair”
- Conference Proceeding – PSRS 2020 – Christopher Panebianco, Sanjna Rao, et al. – “Genipin-Crosslinked Fibrin Seeded with Oxidized Alginate Microbeads as a Novel Composite Biomaterial Strategy for Intervertebral Disc Cell Delivery”
- Conference Proceeding – ORS 2021 – Tyler Distefano (presenter), Keti Vaso, et al. – “Hydrogel-embedded PLGA Microspheres for the Delivery of hMSC-derived Exosomes for Intervertebral Disc Repair”
- Conference Proceeding – ORS 2021 – Tyler Distefano, Keti Vaso, et al. – “hMSC-derived Exosomes as a Stem Cell-free Strategy for Biologically Active Annulus Fibrosus Repair”
- Conference Proceeding – ORS 2021 – Christopher Panebianco (presenter), Sanjna Rao, et al. – “Genipin-Crosslinked Fibrin Seeded with Oxidized Alginate Microbeads as a Novel Composite Biomaterial Strategy for Intervertebral Disc Cell Delivery”
- Abstract Submitted – 10th Annual Musculoskeletal Repair and Regeneration Symposium – Christopher Panebianco (presenter), Sanjna Rao – “Novel High-Modulus Cell-Delivery Composite Biomaterial for Annulus Fibrosus”
- Conference Proceeding – AIChE 2021 – Christopher Panebianco (presenter), Sanjna Rao, et al. – “Degradable Oxidized Alginate Microbeads Promote Cell Viability and Extracellular Matrix Synthesis within Genipin-Crosslinked Fibrin Composite Hydrogel Constructs”
- Conference Proceeding – AIChE 2021 – Keti Vaso (presenter), et al. – “Human Mesenchymal Stem Cell-Derived Exosomes for Biologically Active Annulus Fibrosus Repair”
- Conference Proceeding – AIChE 2021 – Sanjna Rao (presenter) and Chrisopher Panebianco, et al. – “Novel High-Modulus Cell-Delivery Composite Biomaterial for Intervertebral Disc Repair and Regeneration” (Rao, S. Awarded 3rd Place in Materials Engineering and Science Poster Competition)
- Conference Proceeding– ORS 2022 – Christopher Panebianco (presenter), Sanjna Rao, et al. – “Cell-Laden Oxidized Alginate Microbeads Seeded in Genipin-Crosslinked Fibrin Hydrogels for Intervertebral Disc Cell Delivery: Long-Term Evaluation of a Composite Biomaterial for Annulus Fibrosus Repair”
- Conference Proceeding – ISSLS 2022 – Christopher Panebianco (presenter), Sanjna Rao, et al. – “Cell-Laden Injectable High-Modulus Biomaterial Composites Repair Intervertebral Discs Under Physiological Loading"