Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats

Abstract

A tissue-engineered bone biomimetic device was developed to regenerate calvaria critical-sized defects (CSDs) in athymic rats. Well-documented evidence clearly confirms that left untreated, CSDs will not spontaneously regenerate bone. To accomplish regeneration, four candidate treatments were assessed: porous poly(D,L-lactide) and type I collagen (PLC), PLC and human osteoblast precursor cells (OPCs) at 2 x 10(5) (PLC/OPCs), PLC and 50 microg of recombinant human bone morphogenetic protein-2 (PLC/rhBMP-2), and PLC/OPCs/rhBMP-2 (the bone biomimetic device). The hypotheses for this study were PLC/OPCs/rhBMP-2 would promote more new bone formation in CSDs than the other treatments and the amount of bone formation would be time dependent. To test the hypotheses, outcomes from treatments were measured at 2 and 4 weeks postoperatively by radiomorphometry for percent radiopacity and by histomorphometry for square millimeters of new bone formation. Data were analyzed by analysis of variance and Fisher's protected least significant difference for multiple comparisons with p< or = 0.05. At 2 and 4 weeks, radiomorphometric data revealed PLC/rhBMP-2 and PLC/OPCs/rhBMP-2 promoted significantly more radiopacity than either PLC or PLC/OPCs. Histomorphometry data at 2 and 4 weeks indicated significantly more new bone formation for PLC/rhBMP-2, PLC/OPCs/rhBMP-2, and PLC/OPCs compared to PLC. By 4 weeks, PLC/OPCs/rhBMP-2 and PLC/rhBMP-2 had regenerated the CSDs with more new bone than the other treatments; the quantity of bone at 4 weeks for these treatments was greater than at 2 weeks.

The effect of hydrogel charge density on cell attachment

“…Each grafting approach has associated risks and complications leading to the desire to design a bioengineered artificial matrix or scaffold that can act as a microarchitectural structure with sufficient surface area for cell adhesion, migration, proliferation, and differentiation of an appropriate in situ tissue. There have been studies of osteoblast and fibroblast interactions with biomaterials that could be used clinically for promoting tissue growth [2,12]. However, few have considered the selective advantage of hydrogel materials in selective growth patterns of osteoblasts and fibroblasts on the scaffolding with respect to early cellular adhesion events.…”

Bone regeneration in a rat cranial defect with delivery of PEI-condensed plasmid DNA encoding for bone morphogenetic protein-4 (BMP-4)

“…43 This report investigates the effects of delivery of PEI-condensed plasmid DNA encoding for BMP-4 from macroporous PLGA scaffolds in bone regeneration. The utility of this system for bone regeneration was evaluated utilizing a cranial critical-sized defect model, 13,44 as a critical-sized defect allows one to clearly identify the effect of the intervention on bone regeneration. This system provides a platform that potentially allows osteoprogenitors or other cell types (eg, fibroblasts) surrounding the defect area to migrate into the defect site, and be transfected by the PEI-condensed plasmid DNA associated with the scaffold.…”

In VitroCharacterization of Immune-Related Properties of Human Fetal Bone Cells for Potential Tissue Engineering Applications

“…5 The use of bone marrow-derived MSCs (BM-MSCs) seems also to represent a promising approach. Local delivery of purified MSCs was used for spine fusion, 6 segmental bone defects, 2 and craniotomy defects.…”

“…Alternatively to the reimplantation of MSCs, an osteoprogenitor cell line (OPC-1) has been established 21 and used in combination with a porous carrier and recombinant human bone morphogenic protein-2, showing synergistic effects on osteoinduction in vivo. 5 The use of human fetal bone cells for tissue engineering has recently been described. Fetal bone cells were shown to proliferate, differentiate, and finally to mineralize their extracellular matrix in vitro.…”