Degradable hydrogel scaffolds for in vivo delivery of single and dual growth factors in cartilage repair  T.A. Holland, Ph.D., E.W.H. Bodde, M.D., V.M.J.I.

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Degradable hydrogel scaffolds for in vivo delivery of single and dual growth factors in cartilage repair  T.A. Holland, Ph.D., E.W.H. Bodde, M.D., V.M.J.I. Cuijpers, B.Sc., L.S. Baggett, Ph.D., Y. Tabata, Ph.D., A.G. Mikos, Ph.D., J.A. Jansen, Ph.D., D.D.S.  Osteoarthritis and Cartilage  Volume 15, Issue 2, Pages 187-197 (February 2007) DOI: 10.1016/j.joca.2006.07.006 Copyright © 2006 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 In vitro IGF-1 (●) and TGF-β1 (○) release from OPF scaffolds in PBS (a) and in CC-PBS (b). Data are shown as average cumulative release with error bars representing ±SD (n=6). Osteoarthritis and Cartilage 2007 15, 187-197DOI: (10.1016/j.joca.2006.07.006) Copyright © 2006 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 Histological section displaying fibrocartilage in-growth near the chondral defect margins and significant subchondral restoration. The boxed regions in (a) (2× magnification) are shown at 20× magnification to illustrate the spherical shape of cartilage cells in the neo-surface (b) and small regions of remodeling tissue in subchondral region (c). This defect was treated by IGF-1 delivery. Osteoarthritis and Cartilage 2007 15, 187-197DOI: (10.1016/j.joca.2006.07.006) Copyright © 2006 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 Comparison of results following histomorphometric analysis of the overall defect (a), subchondral region (b), and chondral region (c). Data are shown as average scores with error bars representing ±SD (n=10–11 defects per treatment). Scores with significant differences (P<0.05) compared to untreated defects (control), defects treated by TGF-β1-loaded scaffolds, and defects treated by dual TGF-β1&IGF-1-loaded scaffolds are, respectively, indicated by C, T, and D. Untreated control, □; TGF-β1-delivery, ▤; TGF-β1&IGF-1 delivery, ■; IGF-1 delivery, ▥. Osteoarthritis and Cartilage 2007 15, 187-197DOI: (10.1016/j.joca.2006.07.006) Copyright © 2006 Osteoarthritis Research Society International Terms and Conditions

Fig. 4 Histological section displaying the thick fibrous tissue commonly observed at the neo-surface and that often accompanied un-remodeled cartilaginous regions in the subchondral zone. The boxed regions in (a) (2× magnification) are shown at 20× magnification to illustrate the cell morphology observed in portions of the chondral (b) and subchondral (c) regions. This defect was untreated. Osteoarthritis and Cartilage 2007 15, 187-197DOI: (10.1016/j.joca.2006.07.006) Copyright © 2006 Osteoarthritis Research Society International Terms and Conditions

Fig. 5 Histological section displaying the most striking example of cartilaginous tissue remaining in the subchondral defect area. The boxed regions in (a) (2× magnification) are shown at 20× magnification to illustrate the fibrous tissue and hypertrophic cartilage observed in portions of the chondral (b) and subchondral (c) regions, respectively. This defect was treated by IGF-1 delivery. Osteoarthritis and Cartilage 2007 15, 187-197DOI: (10.1016/j.joca.2006.07.006) Copyright © 2006 Osteoarthritis Research Society International Terms and Conditions

Fig. 6 Histological section displaying excessive fibrous tissue growth into the joint space and significant subchondral restoration. The boxed regions in (a) (2× magnification) are shown at 20× magnification to illustrate the spindle-like cells in the neo-surface (b) and small regions of remodeling tissue in subchondral region (c). This defect was treated by TGF-β1 delivery. Osteoarthritis and Cartilage 2007 15, 187-197DOI: (10.1016/j.joca.2006.07.006) Copyright © 2006 Osteoarthritis Research Society International Terms and Conditions

Fig. 7 Histological section displaying thin fibrous tissue growth along the surface of a joint with complete subchondral restoration. The boxed regions in (a) (2× magnification) are shown at 20× magnification to illustrate the morphology of the fibrous neo-surface (b) and the mature bone in the subchondral region (c). This defect was treated by TGF-β1&IGF-1 delivery. Osteoarthritis and Cartilage 2007 15, 187-197DOI: (10.1016/j.joca.2006.07.006) Copyright © 2006 Osteoarthritis Research Society International Terms and Conditions