Degradable orthopedic repair devices would provide significant clinical benefits to overcome current limitations in bone remodeling, degradation kinetics and bone integration. Current options are limited primarily to nondegradable metals which have become the gold standard for orthopedic repairs due to robust mechanical properties and ease of implantation, while limitations of stress shielding, infections, bone remodeling and second surgical removals have shifted significant interest toward degradable devices. Orthopedic screws and plates composed of polylactic and polyglycolic acids have become lead candidates for degradable hardware with a reduced need for removal and improved bone remodeling. However, polylactic and polyglycolic acid screws and plates are associated with inflammatory reactions due to degradation products, osteolysis and incomplete bone remodeling. Thus, orthopedic hardware that has appropriate mechanical properties, tunable and full degradation and is pro-osteogenic would have a major impact on orthopedic repairs in promoting accelerated healing, reducing second surgeries and improving long-term patient outcomes. Our long term goal is to develop fully degradable screws, plates and rods using silk protein functionalized by bioactive molecules to promote healthy bone remodeling and integration. The objective of the proposed research is to determine the ability of the proposed silk format to meet the structural needs of degradable orthopedic systems and successfully direct pro-osteogenic remodeling. We hypothesize that functionalized silk orthopedic hardware can be tuned to fully degrade over a 6-12 month time while promoting osteointegration to optimize utility in orthopedic repairs and meeting mechanical requirements. Our extensive preliminary in vitro and in vivo data support this hypothesis. The rationale for this research is to gain fundamental insight into the role of functionalized and degradable orthopedic screws and plates in accelerating healing and directing successful bone remodeling. The anticipated outcomes are expected to have a substantial positive impact on orthopedic repairs by presenting hardware designs capable of meeting mechanical needs of fracture fixation and addressing current limitations and complications. An interdisciplinary team of investigators who have a history of collaborative efforts will conduct the studies [David Kaplan - silk biomaterials, bioengineering, Ara Nazarian - biomechanics/biomiaging and animal studies, Sam Lin and Brian Snyder - orthopedic surgeons].
Degradable orthopedic repair devices that promote healing, tissue integration and avoid second surgeries would have a major impact on bone repairs, bone fasteners and on rapidly growing surgical needs such as for children. New device options that can proactively control bone remodeling, provide protection against infections and yet fully resorb over time would revolutionize many clinical approaches in the field of orthopedics.
| James, Eric N; Van Doren, Emily; Li, Chunmei et al. (2018) Silk Biomaterials-Mediated miRNA Functionalized Orthopedic Devices. Tissue Eng Part A : |
| MartÃn-Moldes, Zaira; Ebrahimi, Davoud; Plowright, Robyn et al. (2018) Intracellular Pathways Involved in Bone Regeneration Triggered by Recombinant Silk-silica Chimeras. Adv Funct Mater 28: |
| Jastrzebska, Katarzyna; Florczak, Anna; Kucharczyk, Kamil et al. (2018) Delivery of chemotherapeutics using spheres made of bioengineered spider silks derived from MaSp1 and MaSp2 proteins. Nanomedicine (Lond) 13:439-454 |
| Rodriguez, Maria J; Dixon, Thomas A; Cohen, Eliad et al. (2018) 3D freeform printing of silk fibroin. Acta Biomater 71:379-387 |
| Guo, Jin; Li, Chunmei; Ling, Shengjie et al. (2017) Multiscale design and synthesis of biomimetic gradient protein/biosilica composites for interfacial tissue engineering. Biomaterials 145:44-55 |
| Li, Chunmei; Hotz, Blake; Ling, Shengjie et al. (2016) Regenerated silk materials for functionalized silk orthopedic devices by mimicking natural processing. Biomaterials 110:24-33 |
| Thurber, Amy E; Omenetto, Fiorenzo G; Kaplan, David L (2015) In vivo bioresponses to silk proteins. Biomaterials 71:145-157 |
| Reeves, Andrew R D; Spiller, Kara L; Freytes, Donald O et al. (2015) Controlled release of cytokines using silk-biomaterials for macrophage polarization. Biomaterials 73:272-83 |
| Li, Adrian B; Kluge, Jonathan A; Guziewicz, Nicholas A et al. (2015) Silk-based stabilization of biomacromolecules. J Control Release 219:416-430 |
