Poster B4 - Growth-Factor Mimetic Hydrogels Upregulate Pro-Angiogenic Signaling Cascades for Tissue Regenerative Applications

Friday, October 25, 2024

10:00 AM – 11:00 AM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

OW

Owen West

Undergraduate
New Jersey Institute of Technology
Newark, New Jersey, United States

Co-Author(s)

Bobak Shadpoor, MS (he/him/his)

Graduate Student
New Jersey Institute of Technology
Newark, New Jersey, United States
Abhishek Roy, BS

PhD Student
New Jersey Institute of Technology
Newark, New Jersey, United States
JD

Joseph Dodd-o (he/him/his)

Graduate Student
New Jersey Institute of Technology
Newark, New Jersey, United States

Last Author(s)

CH

Corey Heffernan, PhD

Res Asst Prof
NJIT
Newark, New Jersey, United States

Primary Investigator(s)

Vivek Kumar, PhD

Associate Professor
New Jersey Institute of Technology
Newark, New Jersey, United States

Introduction: Peripheral Artery Disease and diabetic wounds are clinically impactful maladies which require sufficient improvement of site-specific tissue regeneration for improved patient outcomes to be realized [1,2]. Self-assembling peptide hydrogels (SAPHs) represent a biomaterial platform that is being explored as an off-the-shelf, injectable, localized, tissue regenerative therapeutic. SAPHs are easily tunable, with their fibrous scaffold organization being minimally affected by the addition of short ( < 20 amino acids) bioactive motifs. Modified peptide constructs SLan and SLIGF (fig. 1) utilize growth factor-receptor agonizing domains that bind to their receptors upon cellular assimilation to the scaffold, resulting in proangiogenic signaling and enhanced tissue regenerative capabilities[3,4]. In this study, the ability of SLIGF and SLan (modified variants of the SAP K1) to positively influence tissue-regenerative cell signaling is demonstrated via quantitative Western Blot. This investigation aims to compare the effects of these peptides across various cell types, showing therapeutic potential to be applied to various kinds of tissue malformations.

Materials and

Methods: The rationally designed peptide sequences were synthesized in-house by solid phase peptide synthesis and resuspended to form hydrogels. To assess the effects on cell signaling, peptides (10 µM) were incubated with C2C12 or HUVEC cells for 10 minutes. Cell lysate was subsequently collected and electrophoresed. Quantitative Western Blot analysis confirmed phospho-activated ERK1/2 was upregulated (total ERK1/2 used as loading control). Ongoing studies will analyze the activation of ERK1/2, VEGFR2, & IGF-1R in HUVECs and HEK293s.

Results, Conclusions, and Discussions: The preliminary data performed on C2C12 myoblasts indicate that the addition of either growth factor-receptor agonizing domain upregulates the tissue-regenerative ERK1/2 signaling pathway. The growth-factor mimetic peptides SLIGF and SLan, retaining the injectable scaffold characteristics of K1, show preliminary emergence of a “two-pronged” therapeutic ability. Further investigation on the signaling ability in HUVECs and HEK293 will broaden the therapeutic contexts to revascularization and cellular differentiation, respectively. Additional studies will evaluate the signaling capability of SLan:K1 ratios and mixed SLan:SLIGF preparations.

Acknowledgements (Optional):

References:
1. American Diabetes, A., Economic Costs of Diabetes in the U.S. in 2017. Diabetes Care, (2018)
2. Kohn et al., Cost and inpatient burden of peripheral artery disease: Findings from the National Inpatient Sample, Atherosclerosis (2019)
3. Kim et al., Angiogenic Hydrogels to Accelerate Early Wound Healing, Macromolecular Bioscience (2022)
4. Roy et al., Self-Assembling Peptides with Insulin-like Growth Factor Mimicry, ACS Applied Materials and Interfaces (2024)

Funding acknowledgements: NIDCR R01DE031812 (PI) | NIDCR R01DE029321 (Co-I) | NINDS R61NS127271 (Co-I) | NIAMS R21AR077835 (MPI) | NIAMS R01AR080895 (Co-I)