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Regulating Bone Formation via Controlled Scaffold Degradation

¹ Departments of Biomedical Engineering,
² Chemical Engineering, and
³ Biologic and Materials Sciences, Room 5213 Dental School, 1011 North University, University of Michigan, Ann Arbor, MI 48109-1078, USA;

View larger version (44K): [in this window] [in a new window]   Figure 1. Gamma-irradiation decreases the average molecular weight of alginate polymer chains and increases its biodegradation rate in vivo. (A) Average molecular weight of alginate as a function of radiation dose. Experimental values are reported as mean (N = 3) ± SD. Gross appearance of explanted gels formed from (B) 0 Mrad 2% alginate and (C) 8 Mrad 3% alginate after 12 wks’ subcutaneous implantation in the backs of SCID mice. [Size bar in photomicrographs (B) and (C) represents 6 mm.] Photomicrographs of H/E-stained histological sections of (D) non-irradiated and (E) 8-Mrad-irradiated hydrogels at 12 wks. [Size bar in photomicrographs (D) and (E) represents 200 µm. A = residual alginate, F = fibrous tissue.] (F) Change in implant mass over time. [Experimental values are reported as mean (N = 4-5) ± SD. (*) indicates a statistically significant (P < 0.05) difference in implant mass between irradiated alginate and non-irradiated alginate control at a specific time point. () 0 Mrad 2% alginate, (•) 5 Mrad 2% alginate, () 8 Mrad 3% alginate.]

View larger version (129K): [in this window] [in a new window]   Figure 2. Transplantation of osteoblasts in alginate with increased degradation rate resulted in qualitatively improved bone formation. Photomicrographs of (A-D) H/E and (E-F) Goldner’s Trichrome-stained histological sections of tissues formed from primary rat calvarial osteoblasts transplanted in (A,C,E) 0 Mrad 2% alginate-G4RGDSP and (B,D,F) 8 Mrad 2% alginate-G4RGDSP after 6, 13, and 21 wks’ subcutaneous implantation. [Size bar in photomicrographs represents 200 µm. A = residual alginate, B = bone tissue.]

View larger version (17K): [in this window] [in a new window]   Figure 3. Transplantation of osteoblasts in alginate with increased degradation rate resulted in quantitatively improved bone formation. Change in tissue-engineered (A) bone mass, (B) BMC, and (C) BMD over time. (D) Histomorphometric quantification of implant bone fraction over time. [Experimental values are reported as mean (N = 4-5) ± SD. (*) indicates a statistically significant (P < 0.05) difference between irradiated alginate and non-irradiated alginate control at a specific time point.]

View larger version (52K): [in this window] [in a new window]   Figure 4. Increased polymer degradation rate results in improved bone microarchitecture as demonstrated by µCT images. µCT image slices of (A) 0 Mrad 2% alginate-G4RGDSP + PRCO and (B) 8 Mrad 2% alginate-G4RGDSP + PRCO after 21 wks. [Image reconstructions are at a resolution of 18 µm; size bars represent 3 mm.]

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