Smart Scaffolds for Tissue Repair and Regenerative Medicine

Description:

Smart Scaffolds for Tissue Repair and Regenerative Medicine

Princeton Docket # 12-2742

A major challenge in biomedical research with application to regenerative medicine is to cause cells to assemble into particular orientations or alignments on a scaffold device in order to generate tissues with the required cellular organization and mechanical properties. As alignment is key to tissue regeneration, this novel method rapidly generates an aligned monolayer of confluent cells that assemble a "natural" extracellular matrix (ECM). As the resulting ECM is a natural scaffold, it can be decellularized to provide a natural scaffold that has been demonstrated to grow aligned cells^{. 1}

In combining complementary expertise in chemistry and biology to devise novel ways to integrate synthetic materials with living tissues, researchers in the Chemistry and Molecular Biology departments, Princeton University, have approached this challenge by generating cell-adhesive chemical patterns in nano-scale and micro-scale dimensions using a technique discovered for surface modifying soft polymers that have utility as bio-scaffold materials. This approach should have wide applicability in bioengineering and biomaterials design, and may provide the basis for superior outcomes using tissue repair scaffold materials. By directing cell shape and orientation using chemically patterned surfaces, cell behavior can be controlled which will provide a system for the development of materials and devices for tissue repair and regenerative medicine.

Using a proprietary nanoscale chemical layer to attach a non-biologic cell adhesive molecule to the substrate, the use of specific cell adhesion receptors is eliminated which expands the range of cells that can interact with the substrate. Additionally this novel method and “Smart” device does not encumber receptors that may be needed for cell spreading, or extracellular interactions which are key to the successful cellular organization and alignment of the tissue.

Applications

· Ex situ and in situ tissue repair and regeneration

· Tissue Engineering

· Wound healing

· Nerve regeneration

Advantages

· Use of “Smart” scaffolds to control cell growth and alignment

· Scalable, easy method using photolithography

· Eliminates use of specific cell adhesion receptors

· Autologous ECM for tissue repair

Results to date:

Using this proprietary method we have prepared a confluent layer of aligned cells which has been demonstrated in the published literature. ¹ This is likely the first demonstration to show that cells assemble their ECM in alignment with the cell adhesive chemical pattern and that the ECM alignment is maintained following decellularization. Neural cells adhere to the decellularized matrix and extend their neurites oriented in line with the ECM fibrils. Several cells types including human mesenchymal stem cells proliferate in register with the chemical surface patterns. These results support the application of this technology to spatially direct the assembly of a broad range of tissue specific ECMs by using the appropriate matrix –forming cells. ¹

Further in vivo studies are ongoing.

Publications:

¹Singh, S., Bandini, S.B., Donnelly, P.E., Schwartz, J., Schwarzbauer, J.E., A cell-assembled, spatially aligned extracellular matrix to promote directed tissue development, Journal of Materials B Biol Med, 2014, March 21;2(11) 1449-1453.

Donnelly, P.E., Jones, C.M., Bandini, S.B., Singh,S., Schwartz, J., Schwarzbauer, J.E., A simple nanoscale interface directs alignment of a confluent cell layer on oxide and polymer surfaces, Journal of Materials Chemistry B, 2013, 1, 3553-3561.

Dennes, T.J.; Schwartz, J., Controlling cell adhesion on polyurethanes, Soft Matter 2008, 4, 86.

Dennes, T.J.; Schwartz, J., A Nanoscale Metal Alkoxide/Oxide Adhesion Layer Enables Spatially Controlled metallization of Polymer Surfaces, ACS Appl. Mater. Interfaces 2009, 1, 2119.

Dennes, T.J.; Hunt, G.C.; Schwarzbauer, J.E.; Schwartz, J., High Yield Activation of Scaffold Polymer Surfaces to Attach Cell Adhesion Molecules, J. Am. Chem.Soc. 2007,129, 93.

Inventors

Jeffrey Schwartz, Professor of Chemistry, Department of Chemistry, Princeton University

Research in the lab of Professor Schwartz is focused on the design, synthesis and characterization of “functional” interfaces for use in biomedical devices and molecular electronics A recipient of an NFL Charities grant to fund research into joint and ligament replacement, one area of Professor Schwartz’s research is to learn how to control cell behavior on a surface to enable tissue integration with a synthetic of interest in the biomedical area. He collaborates extensively with the research group of Professor Jean Schwarzbauer in Molecular Biology at Princeton.

Jean E. Schwarzbauer, Professor of Molecular Biology, Department of Molecular Biology, Princeton University

Research in Professor Schwarzbauer’s lab focuses on the role of the extracellular matrix (ECM) and integrin signaling in cell adhesion and cell migration. Most of the lab studies fibronectin a major component of the ECM and important integrin ligand. The Schwarzbauer lab collaborates with Professor Jeff Schwartz in the Chemistry department to develop chemically-modified substrates with defined compositions of adhesion protein domains.

Intellectual Property status and commercial development

Patent protection is pending.

Princeton is seeking to identify commercial partners for the further development and commercialization of this technology.