Abstract
Introduction: The aim of the current investigation to study the inherent ability of biomaterial scaffolds to regenerate bone defects without osteoinductive growth factors. We have developed a biosynthetic hybrid scaffold that mimics the biofunctionality of the provisional fibrin matrix which regulated the initial stages of in vivo bone regeneration. The material is comprised of a fibrinogen backbone and polyethylene glycol (PEG) cross-links that regulate the strength, durability, and degradation of the matrix during the healing process. Precise control over the degradability of the hydrogel scaffold provides the ability to systematically regulate the cellular infiltration associated with fracture healing. Furthermore, improved physical strength (over purified native fibrin clots) enables superior handling properties and stable in situ fixation.
Materials & Methods: In the current study, a 7-mm critical size defect is created in the right tibia of female Sprague-Dawley rats (age 3–4 months); an external fixator is placed proximal and distal to the mid-section of the tibia. Pre-cast fibrinogen-PEG cylindrical hydro-gels (3-mm dia, 7-mm long) are placed into the site of the defect. Three different hydrogel compositions are tested: 1:1, 1:2, and 1:3 fibrinogen to PEG. Independent experiments demonstrate that higher concentrations of PEG give the hydrogels slower degradation kinetics. Radiographs, post operative and during follow-up, and histological evaluation were done.
Results & Discussion: Both radiography and histological evaluation reveals extensive and widespread periosteal new bone formation. Post-operative radiographs show the formation of a periosteal callus in the gap region of treated animals after five weeks compared to immediately following excision (Figure 1, right). Five weeks post-operatively, histological sections stained with H& E reveal a thick covering of newly formed and moderately differentiated lamellar-fibred bone alongside lengthy stretches of the original cortex. There are large amounts of closely packed trabeculae of recently deposited, woven-fibered bone wherever there are empty spaces of the hydrogel scaffold. These trabeculae join at their perimeters with the preexisting bone. We also demonstrate a clear relationship between the composition of the hydrogel and the synthesis of new bone in the defect site. In conclusion, we demonstrate the formation of newly synthesized bone in critical size defects in the rat tibia using a biomimetic hydrogel scaffold without the use of exogenous growth factors.
The abstracts were prepared by Ms Orah Naor. Correspondence should be addressed to Israel Orthopaedic Association at PO Box 7845, Haifa 31074, Israel.
