Biological Effects of Collagen Hydrogel-sponge Composite Scaffold and Osteoinduction by Combined Application with BMP

Abstract

We prepared a collagen hydrogel-sponge composite which would serve as a bioactive scaffold for bone engineering. The present study examined the effects of the collagen composite scaffold combined with/without bone morphogenetic protein (BMP) on tissue reaction and osteoinduction after implantation in rat cranial bone defects. In order to create the collagen hydrogel-sponge composite, 1.5% collagen hydrogel cross-linked by ascorbate and copper ion was injected into 4% FC-HAC sponge (6×6×3mm) which was prepared by mixing fibrillar collagen with heat-denatured collagen. A bone defect (4×4×0.5mm) was made in a calvalium of 87 Wistar male rats and the rats were assigned to five experimental groups according to the implantation. The defects were filled with the collagen hydrogel-sponge composite loaded with BMP-2 (BGS group, n=18), the collagen hydrogel-sponge composite (GS group, n=19), the FC-HAC sponge containing BMP-2 (BS group, n=17), the FC-HAC sponge (S group, n=17), or no materials (C group, n=16). Animals were euthanized after 5, 10, and 15 days, and the specimens were analyzed histomorphologically. In the BGS and GS groups, fibroblastic and osteoblastic cells proliferated on the inner side of the collagen hydrogel-sponge composite. Few inflammatory cells were seen in the connective tissue around the remnants of collagen materials. At day 15, newly formed bone area and height in the BGS group were significantly greater than those in any other group (p<0.01). A significantly greater bone induction was measured in the GS group than in the C group (p<0.01). Implanted collagen material in the BGS group significantly disappeared compared to the S group (p<0.05). These results suggested that collagen hydrogel-sponge composite encouraged the proliferation of fibroblastic and osteoblastic cells, and rapid replacement for regenerating tissue and space making, and has a better potential as a scaffold for osteoinduction by combined implantation of BMP.