Successful clinical repair and regeneration of bone remain a significant challenge in orthopedic surgery.  Currently, autografts are the clinically preferred grafting material for osseous repair and replacement.  They are, however, limited in supply, restricted by anatomical incompatibilities and are often associated with risk of donor site morbidity.  Recently, with the advent of tissue engineering, alternatives to autografts have emerged.  In this approach, host cells are obtained from the patient by biopsy and subsequently seeded on supporting constructs in a controlled environment, where the cells are encouraged to rapidly multiply and to synthesize mineralized tissue in vitro. 

The ideal bone replacement scaffold should be biodegradable, porous, possess mechanical properties matching that of human bone, and able to stimulate new bone formation.  A biodegradable scaffold is particularly advantageous as it will eventually be replaced by host tissue.  Biodegradable polymers currently used in orthopedic applications include polylactide (PLA), polyglycolide (PLG) and their co-polymers (PLGA).  The biocompatibility of these polymers has been well documented. They have been approved by the FDA, and they have been used as surgical sutures and fixation devices with extended success. 

Several researchers have implanted 3-D scaffolds of various synthetic and natural materials to recreate the 3-D environment in vitro and to facilitate tissue synthesis. However, tissue ingrowth into such structures is often limited due to insufficient transport and exchange of oxygen, nutrients, and waste throughout the scaffold. 

To overcome these limitations a team of surgeons and engineers from Drexel University, The University of Pennsylvania and The Wistar Institute has designed a lighter-than-water, 3-D scaffolds of degradable PLGA that are specifically suited for bone tissue engineering in the High Aspect Ratio Vessel rotating bioreactor.  The motion of these constructs in the rotating bioreactor provides a convective transport flux which enhances nutrient supply and waste product removal within the scaffold.  In addition, the trajectory of lighter-than-water scaffolds may be controlled in order to eliminate damaging collisions with the bioreactor wall during culturing. This combination of optimally designed 3-D configuration and fluid flow, in the absence of wall collisions, enhances the rate and extent of mineralized tissue synthesis in vitro, and represents great promise for the development of new technologies for the tissue engineering of bone.

The researchers have fabricated a 3-D, biocompatible, biodegradable polymer-based scaffold, and have demonstrated its ability to support the growth and phenotypic expression of osteoblast-like cells in a bioreactor environment.  PLGA, in a range of co-polymer ratios, was used as the polymer base of the tissue engineered construct because of its documented degradability and biocompatibility.  The advantage of this approach is that it enables copious production of autograft-like tissue by growing host cells on a supporting substrate designed to stimulate new bone formation, and culturing the cell-construct in an environment where controlled fluid flow further stimulates the formation of mineralized tissue.