Influence of the molecular weight of poly(lactide-co-glycolide) on the in vivo cartilage repair by a construct of poly(lactide-co-glycolide)/fibrin gel/mesenchymal stem cells/transforming growth factor-β1.
The poly(lactide-co-glycolide) (PLGA, LA/GA 75/25) sponges with different weight average molecular weights (Mw 52, 122, and 177 kDa) were fabricated and were used to build the constructs of PLGA/fibrin gel/mesenchymal stem cells (MSCs)/transforming growth factor-β1 (TGF-β1). The PLGA 177 with the highest Mw (177 kDa) had the fastest degradation rate at the initial stage, whereas the PLGA 122 had the moderate degradation rate and smallest mass loss. After implantation in rabbit knees for 12 weeks, the full-thickness defects (both cartilage and subchondral bone were destroyed with a diameter and depth of 4 mm) repaired by the PLGA 122 group had formed a hyaline cartilage-like tissue with abundant glycosaminoglycans on the top layer and subchondral bone on the bottom layer. The group also achieved the best macroscopic (11.3 ± 0.8) and histological scoring (Wakitani, 0.5 ± 0.6). To unveil the mechanism of the cartilage repair outcome and the PLGA degradation behaviors, the chondrogenesis-related genes, inflammatory cytokines, and matrix metalloproteinase (MMP) activity were analyzed by quantitative reverse transcription-polymerase chain reaction at week 1, 3, and 6 postsurgery. At each time point, the regenerated tissues by the PLGA 122 group had the highest mRNA expression of SOX9 and collagen type II, but the smallest mRNA expression of interleukin-1β and tumor necrosis factor α, and MMP-13 and MMP-3. In summary, as a scaffolding matrix, the PLGA with different Mw shows a huge difference in cartilage regeneration in vivo. The one with a moderate Mw (122 kDa) causes the weakest inflammatory response and results in the best cartilage regeneration.
1 MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou, China .
Bo
B
Li
Junzhou
J
Yang
Lie
L
Ma
Feifei
F
Li
Zhengyuan
Z
Tu
Changyou
C
Gao
D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000473:pathology*; D002417:Cattle; D020219:Chondrogenesis / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D005337:Fibrin / Q000494:pharmacology; D005782:Gels; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D011098:Polyglactin 910 / Q000737:chemistry* / Q000494:pharmacology; D011817:Rabbits; D013194:Staining and Labeling; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D016207:Cytokines; D005782:Gels; D018836:Inflammation Mediators; D053773:Transforming Growth Factor beta1; D011098:Polyglactin 910; D005337:Fibrin; D020782:Matrix Metalloproteinases