Polymeric Biomaterials

Shape Memory Polymers as Biomaterial

This CAREER project aims to elucidate the underlying mechanism of the plasticization-induced shape memory effect of thiol-ene-based polymers. The model application for this material will be heat-shrink tubing that can shrink at bodily conditions (37° C and simulated body fluids) and be used to seal colonic anastomosis.

Shape Memory Cycle

The specific three aims are to

  1. Systematically investigate the effect of crosslink density and chain extender length on the plasticization-induced shape memory effect of thiol-ene-based polymers. Mechanical and thermomechanical measurements inside simulated body fluids will be used to assess shape memory properties and structure-property relationships.
  2. Understand the relationship between material thickness, degree of shape-programming, and radial recovery forces of tube-shaped SMPs to determine optimal design parameters for sufficient shape recovery using the heat shrink tube model.
  3. Demonstrate the functionality of a biomedical heat shrink tube that utilizes the plasticization-induced shape recovery through an ex vivo colon anastomosis model and quantify mechanical and sealing properties.

The proposed research will advance science by filling the gap in the structure-property relationship of thiol-ene-based SMPs that utilize plasticization for their shape recovery, which is essential for designing future devices.

In addition, this innovative biomaterial will allow the broader research community to develop novel biomedical devices tailored to specific tissues and applications. Educational and outreach activities will be implemented to raise excitement, awareness, and interest in the emerging field of smart polymeric biomaterials. These will include a gender- and ethnicity-matched mentor-mentee program, training students from underrepresented groups in the PI’s laboratory, incorporating research discoveries into coursework, and communicating research to the general public at local science slam events.

Thiol-ene Based Shape Memory Polymers

Our research investigates the development and characterization of a novel class of biomaterials known as thiol-ene/acrylate polymers. These polymers hold promise for various biomedical applications due to their flexibility, softening capability, and shape memory properties. However, they often lack the necessary stretchability for wearable or implantable devices. To address this limitation, our research incorporates di-acrylate chain extenders, specifically Polyethylene Glycol Diacrylate (PEGDA), into thiol-ene polymers.

The synthesis process combines 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (TATATO), Trimethylolpropanetris (3-mercaptopropionate) (TMTMP), and PEGDA with different molecular weights. Fourier Transform Infrared (FTIR) spectroscopy confirms complete reaction among the monomers. Uniaxial tensile testing demonstrates the softening and stretching capability of the polymers, with significant reductions in Young’s Modulus and increased fracture strain upon the addition of PEGDA.

Our research also explores the thermomechanical properties of the polymers, highlighting the ability of PEGDA to tune the material’s glass transition temperature (Tg). Additionally, the polymers exhibit shape memory properties, further enhancing their potential for biomedical applications.

There has been research on thiol-ene reactions and their applications in various fields, including wound healing, drug delivery, and tissue engineering. However, there is a gap in the research regarding the synthesis of polymers with combined self-softening, flexibility, stretchability, and shape memory properties suitable for biomedical applications. Our study aims to fill this gap by synthesizing and characterizing such a polymer.

Stretchable polymers have the ability to conform to organ movements, reducing motion artifacts in biomedical devices. Their shape memory property enables them to restore their original configuration post-deformation, making them suitable for minimally invasive devices and surgical applications.

Read more about this research here:

C. Chitrakar, M.A. Torres, P.E. Rocha-Flores, Q. Hu, M. Ecker, Multifaceted Shape Memory Polymer Technology for Biomedical Application: Combining Self-Softening and Stretchability Properties. Polymers202315, 4226.

SMP Bandage to prevent Colonic Anastomotic Leak

After colonic resections that may be necessary in case of cancer or diverticulitis, the two parts of the colon need to be reattached after the procedure. This procedure is called anastomosis and can be done through manual sutures or staples. In any case, there are rates between 1% and 30% of anastomotic dehiscence reported in the literature.1 Anastomotic Leak is defined as a “leak of luminal contents from a surgical join between two hollow viscera.”2 If contents from the inside of the colon leak into the abdominal area, the consequences are various clinical signs like peritonitis; feculent wound, drain discharge, abscess, or fever. “Anastomotic leakage remains today a major cause of postoperative mortality and morbidity in colorectal surgery.”3

In order to minimize the risk of anastomotic leakage, we propose to develop a bandage made of SMP, which can wrap around the colon to seal the reconnected parts from the outside and, therefore, prevent any fluids from getting into the abdominal cavity. The SMP will be fabricated into a tube shape that has a slightly smaller radius than the colon. The tube will then be radially expanded to a radius that is 1.5 times the radius of the colon. The device will be placed at the outside of the colon, covering the part where the anastomosis took place. The polymer will recover its shape due to the plasticization-induced shape memory effect and will wrap tightly around it to seal the colonic part against leakage after surgery. The SMP will be designed to be biodegradable in order to dissolve over the course of 3 to 6 months so that a second surgical procedure will not be necessary. The biodegradability and time span of degradation can be tuned by the number of ester groups in the polymeric backbone and the crosslink density of the polymeric network.

Figure 3. Working principle of the SMP bandage to prevent anastomotic leak. (created in BioRender)

In addition, anti-inflammatory drugs and bioactive compounds that promote wound healing will be loaded into the polymer. This study will serve as a model to test the hypothesis that polymers loaded with bioactive compounds reveal positive effects on the healing process and can serve as a platform technology capable of concurrent drug delivery.

[1] Kingham, T. P.; Pachter, H. L., Colonic Anastomotic Leak: Risk Factors, Diagnosis, and Treatment. Journal of the American College of Surgeons 2009, 208 (2), 269-278.

[2] Peel, A. L.; Taylor, E. W., Proposed definitions for the audit of postoperative infection: a discussion paper. Surgical Infection Study Group. Annals of The Royal College of Surgeons of England 1991, 73 (6), 385-388.  

[3] Alves, A.; Panis, Y.; Trancart, D.; Regimbeau, J.-M.; Pocard, M.; Valleur, P., Factors Associated with Clinically Significant Anastomotic Leakage after Large Bowel Resection: Multivariate Analysis of 707Patients. World Journal of Surgery 2002,26 (4), 499-502

Gelatin-based Hydrogels

We are exploring gelatin-based hydrogels for various biomedical applications. We are interested in hydrogels for:

  • drug delivery systems
  • wound healing patches
  • scaffolds for 3D cell cultures and tissue engineering applications

To improve their biocompatibility, we are utilizing naturally derived polymeric biomaterials such as chitosan, collagen, and gelatin as starting materials for our custom hydrogels. Using materials that are naturally found in nature, and even within our own bodies, greatly reduces the foreign body reaction.

Gelatin methacrylate (GelMA)

Gelatin methacrylate (GelMA) photocrosslinks effectively, making it a widely used biomaterial in tissue engineering due to its favorable biological attributes and customizable physical and mechanical traits. Although GelMA is compatible with various cell types, it elicits distinct cellular responses within GelMA hydrogels, necessitating tailored hydrogels for specific applications.

Syntheses of Gel-MA hydrogels for 3D cell cultures [1]

Our objective is to develop GelMA hydrogels optimized to enhance cell viability, specifically for TC28a2 chondrocytes in a three-dimensional (3D) cell culture setting. [1] We are investigating GelMA synthesis using PBS and 0.25M CB buffer, analyzing the mechanical and physical traits of GelMA hydrogels, and evaluating how varying GelMA crosslinking conditions (GelMA concentration, photoinitiator concentration, and UV exposure time) affect the viability of TC28a2 chondrocytes.

Our results reveal that GelMA synthesis using 0.25M CB buffer leads to a greater degree of methacrylation compared to PBS buffer, and the LAP photoinitiator demonstrates superior efficacy for GelMA gelation compared to Irgacure 2959. Additionally, GelMA concentration predominantly affects the stiffness, porosity, and swelling degree of GelMA hydrogels, while cell viability is impacted by all crosslinking conditions, notably decreasing with increasing GelMA concentration, photoinitiator concentration, and UV exposure time. This study facilitates the optimization of crosslinking conditions to enhance cell viability within GelMA hydrogels, a critical aspect for diverse biomedical applications.

Read our publication related to this research:

[1] Q. Hu, M. A. Torres, H. Pan, S. L. Williams and M. Ecker, M. Precision Engineering of Chondrocyte Microenvironments: Investigating the Optimal Reaction Conditions for Type B Gelatin Methacrylate Hydrogel Matrix for TC28a2 Cells. J. Funct. Biomater., 2024, 15.