Enhancement of periodontal tissue regeneration by locally controlled delivery of insulin-like growth factor-I from dextran-co-gelatin microspheres.
The present work focused on the design of novel hydrogel microspheres based on both dextran- and gelatin-derived biomaterials, and discussed whether locally controlled delivery of IGF-I from dextran-co-gelatin hydrogel microspheres (DG-MP) was useful for periodontal regeneration enhancement. Microspheres were synthesized when gelatin was cooperating with glycidyl methacrylate (GMA) derivatized dextrans (Dex-GMA) and the resultant DG-MP with a hydrogel character of which the cross-linking density could be controlled by the degree of substitution (DS, the number of methacrylates per 100 glucopyranose residues) of Dex-GMA. In this study, three types of DG-MP (DG-MP4.7, DG-MP6.3 and DG-MP7.8) obtained from gelatin and Dex-GMA (differing in DS: 4.7, 6.3 and 7.8 respectively) were prepared and characterized by swelling and degradation properties, drug release kinetics and biological capability in promoting tissue regeneration. By swelling in aqueous positively charged IGF-I solutions, the protein could be encapsulated in DG-MP by polyionic complexation with negatively charged acidic gelatin. No obvious influence of Dex-GMA's DS on DG-MP's configuration and size was observed, and the release and degraded properties showed no significant difference between three types of DG-MP in PBS buffer either. However, high DS of Dex-GMA could lower microsphere's swelling, prolong its degraded time and minimize IGF-I burst release markedly in dextranase-containing PBS, where IGF-I release from a slow release type of microspheres (DG-MP7.8) could be maintained more than 28 days, and an effective protein release kinetics without a significant burst but a relevantly constant release after the initial burst was achieved. IGF-I in DG-MP resulted in more new bone formation in the periodontal defects within 4 or 8 weeks than IGF-I in blood clot directly did (P < 0.01). The observed newly formation of periodontal tissues including the height and percentage of new bone and new cementum on the denuded root surfaces of the furcation area in DG-MP7.8 group were more than that in other groups (P < 0.05). The adequate width of regenerative periodontal ligament (PDL), regular Sharpey's fibers and alveolar bone reconstruction could be observed only in DG-MP7.8 group. These combined results demonstrate that effective release kinetics can be realized by adjusting the DS of Dex-GMA and followed cross-linking density of DG-MP, and that locally controlled delivery of IGF-I from slow release type of DG-MP may serve as a novel therapeutic strategy for periodontal tissue regeneration.
Chen
Fa-ming
FM
Department of Periodontology and Oral Medicine, College of Stomatology, Fourth Military Medical University, 145th Chang-le Road, Xi'an 710032, Shaanxi, China. cfmsunhh@fmmu.edu.cn
Zhao
Yi-min
YM
Wu
Hong
H
Deng
Zhi-hong
ZH
Wang
Qin-tao
QT
Zhou
Wei
W
Liu
Qing
Q
Dong
Guang-ying
GY
Li
Kun
K
Wu
Zhi-fen
ZF
Jin
Yan
Y
D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects; D018360:Crystallography, X-Ray; D003910:Dextranase / Q000737:chemistry; D003911:Dextrans; D004285:Dogs; D016503:Drug Delivery Systems; D005079:Excipients; D017823:Furcation Defects / Q000188:drug therapy / Q000473:pathology; D005780:Gelatin; D005881:Gingiva / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007525:Isoelectric Focusing; D008297:Male; D008863:Microspheres; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects*
D003911:Dextrans; D005079:Excipients; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D005780:Gelatin; D003910:Dextranase