Project Page - Hyeongho(with Jason) : Synthesis of Photocurable Elastomeric Hydrogel

DATE CREATED: Dec. 02. 2008

ACTION PLAN

PROBLEMS IDENTIFIED (PI) / OUTSIDE SKILL REQUIRED (OSR) / RESOLVED (R)

PAPER TITLE: Sugar-based Biodegradable Elastomeric Hydrogel

A) Background

B) Specific Aims

C) General Experimental Approach (Design etc)

D) Design Pitfalls and alternatives

E) Potential Figures

F) Future Directions

A) BACKGROUND

Biomaterials for tissue engineering scaffold should have proper mechanical, chemical, biological properties that are similar to those of real tissues. Photocrosslinkable hydrogels are promising materials for tissue engineering because they can encapsulate cells uniformly, are easy to be processed, and can supply nutrients and oxygens fast to keep cells alive. There are many kinds of hydrogels made of synthetic/natural polymer, but they are mechanically not rigid enough or very expensive. In this project, as a first step of making a great biomaterial for a tissue engineering scaffold, we focus on synthesis of new hydrogels that has better mechanical properties, out of cheap starting materials.

B) SPECIFIC AIMS

AIM 1 - To synthesize a photocrosslinkable hydrogel with improved mechanical properties out of cheap starting materials

C) GENERAL EXPERIMENTAL APPROACH

There are many strategies in making biodegradable elastomer. In this project, we're going to use polycondensation between polyols(which have many -OH groups) and diacids(which have two -COOH groups) to form polyester networks. Among many kinds of polyols, we will try to use sugars(monosaccharides or disaccharides) hypothesizing that the carbon ring structure of sugars will make final product more rigid. Regarding acids, we will try to use malic acid or citric acid, which are hydrophilic compared with other long chain diacid such as sebacic acid. After we react these starting materials and get prepolymer, we will methacrylate it in water to make it photocrosslinkable. We will characterize its chemical structure and composition, analyze mechanical properties, degradation rate, biocompatibility, etc.

<An example of schematic representation of the expected synthesis>

D) DESIGN PITFALLS AND ALTERNATIVES

E) POTENTIAL FIGURES FOR PAPER

Scheme 1. General synthetic scheme of sugar-based polymers

Fig.1. (A) ¹H NMR spectrum of prepolymers and methacrylated polymers

(B) FTIR spectrum of prepolymers, methacrylated polymers, and dried gels

Table 1. Polycondensation conditions, composition by ¹H NMR, molecular weight distribution of prepolymers

Table 2. Polycondensation conditions, Young's modulus, Ultimate tensile stress, Ultimate elongation, Hydration by mass, Sol content, Density,

Crosslink density, Molecular weight between crosslinks of hydrogels

Fig.2. Stress-Strain curve of hydrogels

Fig.3. Mass-loss over time(Degradation rate) in vitro (in vivo?)

Fig.4. MTT assay of 3T3 exposed to prepolymer fractions in medium

Fig.5. Viability of photoencapsulated 3T3 in hydrogels(MTT assay)

(Not sure : Fig.6. In vivo biocompatibility of hydrogels - Images of H&E stained sections)

F) FUTURE DIRECTIONS

1) Cells don't attach to hydrogels well. We should modify the material chemically to induce cell attachment.

2) The final material might not be stretchy enough. We should improve that property not compromising stiffness much.

3) Degradatation rate may be too fast. We should think about the way to slow it down.