Responsively Nanostructured Injectable Protein Hydrogels

Group members working on this project: Matt Glassman
Collaborators: Ali Khademhosseini - Health Sciences and Technology, MIT/Harvard

Hydrogels are an exciting platform technology for biomedical solutions in many high impact areas, from managing chronic ailments such as rheumatoid arthritis and osteoporosis, to treating acute conditions such as hemorrhaging and cancer. Precisely engineered injectable hydrogels could enable minimally-invasive surgical implantation for improved control in the delivery molecular and/or cellular cargo within bioactive, degradable scaffolds. We are developing new methods for engineering shear thinning hydrogels that can be thermoresponsively strengthened post-injection to yield tough implants that can bear significant physiological loads. By utilizing artificially-engineered proteins conjugated to designer polymers, we are synthesizing biomaterials that are finely tuned for protecting and communicating with encapsulated cells, integrating with host tissues at the target site, and executing predefined programs for nanostructure formation and controlled release. Fundamental studies on the structure and mechanics of double physical network hydrogels (which consist of two independent, reversibly-associating networks) will enable the development of enhanced materials to meet clinical demands.

Injectable gels

Hybrid triblock copolymers prepared from associative proteins and thermoresponsive polymers form shear thinning gels with a low yield stress at low temperatures. Upon increasing temperature, an orthogonal network of reinforcing nanostructures is formed that resulted in gels with significantly higher stiffness, resistance to shear thinning, higher toughness, reduced erosion rates, and lower creep compliance at physiological temperatures.

Cryo SEM of gels.

Mammalian cell adhesion studies with 3T3 fibroblasts on a thermoresponsively stiffened protein hydrogel.

Synthetic physically crosslinked and thermoresponsive gels

Group members working on this project: Shengchang Tang
Collaborators: Krystyn van Vliet - Materials Science and Engineering, MIT
      Simona Socrate - Insitute for Soldier Nanotechnologies, MIT

It has been challenging to exactly duplicate the energy dissipation mechanisms of biological tissue using synthetic materials. In this project, we are trying to utilize protein-polymer hydrogel systems to faithfully mimic the mechanical responses of human tissue on different length scales and time scales. Two model synthetic hydrogel systems will be prepared to match the soft tissue (for example, brain tissue) and the stiff tissue (for example, articular cartilage), respectively. By exploring strategies to precisely control the molecular architecture (i.e., hydrophilicity/hydrophobicity, charge density and molecular weight) of the synthetic hydrogels, it is aimed to establish systematic means to control the various molecular interactions (i.e., hydrophobic interaction, electrostatic interaction and physical chain entanglement). By combining experimental results, it is also aimed to develop new theories to elucidate the contribution of various molecular interactions to the mechanical properties of synthetic hydrogels.

Synethic double physical network gel.

Schematic of bottle-brush-like biomacromolecule.

Theoretical Design Considerations for Development of Nanostructured Biomaterials

Group members working on this project: Michelle Sing
Collaborators: Gareth McKinley - Department of Mechanical Engineering, MIT

Internal bleeding is an issue faced by both civilian and military first responders. Current treatment methods involve a combination of fluid resuscitation to replenish fluid flow in the bloodstream and tourniquets to minimize blood loss. This multidisciplinary project focuses on the ability to counteract the latter. Our focus is on the design of an injectable, hemostatic, stimuli-responsive physical hydrogel that can be delivered directly to the location of internal trauma and stop bleeding while simultaneously providing a scaffold for tissue regrowth.

In order to accomplish this, we will center our efforts on the fundamentals of physical gel formation, recovery, and properties before applying that knowledge toward engineering a complex protein hydrogel for our direct application. By looking closely into the structure-property relationships of simple physical gels with advanced mechanical analysis techniques, we will be able to answer key questions about what components make gels recover quickly – a property critical for a gel used to stop internal bleeding.

Interplay between gel structure and properties.

The major focus of this project is to look at the interplay between gel structure and the resultant properties.