**SECOND PLACE**
Student(s): Alexis Kelerchian
Project: Turning the Spatiotemporal Presentation of Growth-Factor Mimetic Peptides in PCL-Based Scaffolds | View Poster (PDF)
Major(s): Bioengineering
Advisor(s): Lesley Chow
Abstract
The osteochondral (OC) interface contains physical and biochemical gradients spanning from cartilage to bone.1 Damage or dysregulation to OC tissue can result in lesions, which can progress into osteoarthritis (OA).1 A complex signalling network of growth factors, antagonists, and other biomolecules direct osteochondral tissue formation in specific, temporal stages.2 Treatments to repair OC tissue and prevent OA must mimic these events to promote native-like tissue regeneration. Biomaterials–based tissue engineering is a promising strategy to promote OC regeneration by enabling spatially and temporally controlled biomolecule presentation. In this work, we exploited end-functionalized polymers to control the spatiotemporal presentation of growth factor (GF)-mimetic peptides. We hypothesize that displaying bioorthogonal click chemistry groups on the scaffold surface will enable us to deliver GF-mimetic peptides to specific locations at specific times under physiological conditions. We synthesized two GF-mimetic peptides based on transforming growth factor β-1 (TGF-β1pep) and bone morphogenetic protein 2 (BMP2pep), GFs that are widely used to induce human mesenchymal stromal cell (hMSC) chondrogenic (cartilage-promoting) and osteogenic (bone-promoting) differentiation, respectively. TGF-β1pep was directly conjugated to polycaprolactone (PCL) to form a peptide-PCL conjugate (TGF-β1pep-PCL).3 A bioorthogonal click chemistry group, methyltetrazine, was conjugated to PCL to create PCL-Mtz. We prepared two different inks by co-dissolving each conjugate with unmodified PCL. The inks were solvent-cast 3D-printed into scaffolds with alternating filaments of TGF-β1pep-PCL and PCL-Mtz. After printing, the functionalized scaffold was incubated with BMP2pep modified with trans–cyclooctene (TCO), which selectively reacts with Mtz. This highly efficient TCO-Mtz reaction enables us to deliver BMP2pep to Mtz-functionalized filaments only and at desired time points during cell culture. This platform provides tunable spatiotemporal control of GF-mimetic peptides to direct osteochondral tissue formation.
References
1. Lepage, S.I.M., et. al. (2019). Beyond Cartilage Repair: The Role of the Osteochondral Unit in Joint Health and Disease. In Tissue Eng. Part B (Vol. 25, No. 2, pp. 114-125).
2. Liu, Heng, et al. “Osteochondrogenesis by TGF-Β3, BMP-2 and Noggin Growth Factor Combinations in an Ex Vivo Muscle Tissue Model: Temporal Function Changes Affecting Tissue Morphogenesis.”
Frontiers in Bioengineering and Biotechnology, vol. 11, Mar. 2023, p. 1140118. DOI.org (Crossref), https://doi.org/10.3389/fbioe.2023.1140118.
3. Seims, Kelly B., et. al. (2021). Strategies to Control or Mimic Growth Factor Activity for Bone, Cartilage, and Osteochondral Tissue Engineering. In Bioconjugate Chemistry (Vol. 32, No. 5, pp.
861-878).
About Alexis Kelerchian
Alexis Kelerchian is a third-year bioengineering student at Lehigh University from Bucks County, Pennsylvania. Kelerchian applies her academic background to her biomaterials research as a member of the Chow Lab. Her research focuses on tuning the presentation of growth factor–mimetic peptides on 3D-printed polycaprolactone (PCL) scaffolds. Conjugating these peptides directly to PCL and using bioorthogonal click chemistries allows Kelerchian to control their spatiotemporal presentation. This platform will enable her to investigate how spatial peptide organization and delivery time influence cell differentiation behavior. This summer, Kelerchian will continue her work in the Chow Lab as a Clare Boothe Luce Research Scholar. Outside the classroom and lab, Kelerchian works as a Head Gryphon, plays on Lehigh University’s Women’s Club Volleyball team, volunteers as an Admissions tour guide, and enjoys reading, drawing, and weightlifting in her free time.