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

A tissue-engineered bone biomimetic device was developed to regenerate calv aria critical-sized defects (CSDs) in athymic rats. Well-documented evidenc e clearly confirms that left untreated, CSDs will not spontaneously regener ate bone. To accomplish regeneration, four candidate treatments were assess ed: porous poly(D,L-lactide) and type I collagen (PLC), PLC and human osteo blast precursor cells (OPCs) at 2 x 10(5) (PLC/OPCS), PLC and 50 mu g of re combinant human bone morphogenetic protein-2 (PLC/rhBMP-2), and PLC/OPCs/rh BMP-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 t reatments and the amount of bone formation would be time dependent. To test the hypotheses, outcomes from treatments were measured at 2 and 4 weeks po stoperatively by radiomorphometry for percent radiopacity and by histomorph ometry for square millimeter of new bone formation. Data were analyzed by a nalysis of variance and Fisher's protected least significant difference for multiple comparisons with p less than or equal to 0.05. At 2 and 4 weeks, radiomorphometric data revealed PLC/rhBMP-2 and PLC/OPCs/rhBMP-2 promoted s ignificantly more radiopacity than either PLC or PLC/PCs. Histomorphometry data at 2 and 4 weeks indicated significantly more new bone formation for P LC/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 t han the other treatments; the quantity of bone at 4 weeks for these treatme nts was greater than at 2 weeks. (C) 1999 John Wiley & Sons, Inc.