Development of composite scaffolds for load-bearing segmental bone defects

Abstract

The need for a suitable tissue-engineered scaffold that can be used to heal load-bearing segmental bone defects (SBDs) is both immediate and increasing. During the past 30 years, various ceramic and polymer scaffolds have been investigated for this application. More recently, while composite scaffolds built using a combination of ceramics and polymeric materials are being investigated in a greater number, very few products have progressed from laboratory benchtop studies to preclinical testing in animals. This review is based on an exhaustive literature search of various composite scaffolds designed to serve as bone regenerative therapies. We analyzed the benefits and drawbacks of different composite scaffold manufacturing techniques, the properties of commonly used ceramics and polymers, and the properties of currently investigated synthetic composite grafts. To follow, a comprehensive review of in vivo models used to test composite scaffolds in SBDs is detailed to serve as a guide to design appropriate translational studies and to identify the challenges that need to be overcome in scaffold design for successful translation. This includes selecting the animal type, determining the anatomical location within the animals, choosing the correct study duration, and finally, an overview of scaffold performance assessment.

Figure 1

(a) Radiograph of open tibial fracture with segmental bone loss as a result of trauma injury. (b) Radiograph of the damaged tibia after intramedullary nail and internal fixation at the extremities. The defect is filled with cement spacer that had been previously impregnated with antibiotic. (c) Radiograph of the defect after 3 and (d) 4 months. Bone healing never occurred, and the fracture is considered a nonunion. Printed with permission from Dr. Steve Morgan [37].

Figure 2

Diagram showing material (top) and biological (bottom) properties of ultimate regenerative bone scaffolds. It is necessary for engineered scaffolds to have both of these properties to promote bone growth. One class of properties alone is not sufficient to promote bone growth in a timely manner. Data originated from [, , , , –42].