Project Page - Femur as a Bioreactor

Created July 10, 2008

Note this is a work in progress please feel free to add comments and suggestions

Many thanks Adam

ACTION PLAN

Paper Title: MATURATION OF TISSUE ENGINEERED CONSTRUCTS IN THE RAT FEMORAL CANAL

A) Specific Aims

B) General Approach

C) Design and Fabrication of tissue engineered construct

D) Design Pitfalls and alternatives

E) Candidate Materials for Evaluation

F) Analytical approach Pre-Implantation

G) Analytical approach Post-Implantation

H) Future Directions

Background: This project will build upon material findings from the in vivo chip. The rat femoral canal presents a favorable environment for tissue growth and development as it contains many of the requisite cells and is connected to the circulation. In addition, past implant related experience has repeatedly demonstrated that fibrous tissue and vascular tissue can develop in this environment. Conveniently the medulary canal is easily accessible and protected from outside forces and movement.

A) SPECIFIC AIMS

AIM 1 - Maturation of microvascular sized tissue engineered constructs in the rat femoral canal

A) Develop, implant and assess a tubular cell laden scaffold from bottom up fabricated hydrogels

B) Develop, implant and assess a tubular cell laden scaffold extruded from a hydrogel and delivered into canal

AIM 2 - Maturation of dual bone and vascular tissue engineered constructs in the rat femoral canal

A) Develop, implant and assess a cell laden scaffold from bottom up fabricated hydrogels containing different cell types (bone, endothelial)

B) GENERAL APPROACH

1) Fabrication of vascular construct from Du's tubular construct. Pass into femoral canal via hollow tube needle.

2) Extrusion of multilayer cell & biomaterial laden hydrogel.

Extrusion of multilayer hydrogel

Delivery of hydrogel to rat femur

Hydrogel in Situ

C) DESIGN AND FABRICATION OF TE PRODUCT

Approach 1 - Bottom up with Du's technology

Approach 2 - Extrusion of Hydrogels. Cell or collagen laden gels extruded to form multilayer hydrogel that mimics the layers of the blood vessel. (Jul 21, 2008)

D) DESIGN PITFALLS AND ALTERNATIVES

E) CANDIDATE MATERIALS FOR INVESTIGATION

Materials and growth factor combinations will be optimized in in vivo chip that assesses vascularization

F) ANALYTICAL APPROACH PRE-IMPLANTATION

G) ANALYTICAL APPROACH POST-IMPLANTATION

H) FUTURE DIRECTIONS

• • Other cell types in a co-cullture in vivo environment.

  • Stem cell maturation