Skip to main content

Advertisement

SpringerLink
Log in

Preparation and Evaluations of Mangiferin-Loaded PLGA Scaffolds for Alveolar Bone Repair Treatment Under the Diabetic Condition

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The aim of the present study was to prepare and evaluate a sustained-release mangiferin scaffold for improving alveolar bone defect repair in diabetes. Mangiferin-loaded poly(D,L-lactide-co-glycolide) (PLGA) scaffolds were prepared using a freeze-drying technique with ice particles as the porogen material. The produced scaffolds were examined using a scanning electron microscope (SEM). Drug content and drug release were detected using a spectrophotometer. Degradation behaviors were monitored as a measure of weight loss and examined using SEM. Then, the scaffolds were incubated with rat bone marrow stromal cells under the diabetic condition in vitro, and cell viability was assessed using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Afterward, the scaffolds were implanted into alveolar bone defects of diabetic rats, and bone repair was examined using hematoxylin and eosin staining. The fabricated scaffolds showed porous structures, with average pore size range from 111.35 to 169.45 μm. A higher PLGA concentration led to decreased average pore size. A lower PLGA concentration or a higher mangiferin concentration resulted in increased drug content. The prepared scaffolds released mangiferin in a sustained manner with relatively low initial burst during 10 weeks. Their degradation ratios gradually increased as degradation proceeded. The mangiferin-loaded scaffolds attenuated cell viability decrease under the diabetic condition in vitro. Moreover, they increased histological scorings of bone regeneration and improved delayed alveolar bone defect healing in diabetic rats. These results suggest that the produced mangiferin-loaded scaffolds may provide a potential approach in the treatment of impaired alveolar bone healing in diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Cramer C, Freisinger E, Jones R, Slakey D, Dupin C, Newsome E, et al. Persistent high glucose concentrations alter the regenerative potential of mesenchymal stem cells. Stem Cells Dev. 2010;19:1875–84.

    Article  CAS  PubMed  Google Scholar 

  2. Jiao H, Xiao E, Graves D. Diabetes and its effect on bone and fracture healing. Curr Osteoporos Rep. 2015;13:327–35.

    Article  PubMed  PubMed Central  Google Scholar 

  3. He H, Liu R, Desta T, Leone C, Gerstenfeld L, Graves D. Diabetes causes decreased osteoclastogenesis, reduced bone formation, and enhanced apoptosis of osteoblastic cells in bacteria stimulated bone loss. Endocrinology. 2004;145:447–52.

    Article  CAS  PubMed  Google Scholar 

  4. Wang Q, Li H, Xiao Y, Li S, Li B, Zhao X, et al. Locally controlled delivery of TNFα antibody from a novel glucose-sensitive scaffold enhances alveolar bone healing in diabetic conditions. J Control Release. 2015;206:232–42.

    Article  CAS  PubMed  Google Scholar 

  5. Rivera D, Hernández I, Merino N, Luque Y, Álvarez A, Martín Y, et al. Mangifera indica L. extract (Vimang) and mangiferin reduce the airway inflammation and Th2 cytokines in murine model of allergic asthma. J Pharm Pharmacol. 2011;63:1336–45.

    Article  CAS  PubMed  Google Scholar 

  6. Márquez L, García-Bueno B, Madrigal J, Leza J. Mangiferin decreases inflammation and oxidative damage in rat brain after stress. Eur J Nutr. 2012;51:729–39.

    Article  PubMed  Google Scholar 

  7. Pal P, Sinha K, Sil P. Mangiferin attenuates diabetic nephropathy by inhibiting oxidative stress mediated signaling cascade, TNFα related and mitochondrial dependent apoptotic pathways in streptozotocin-induced diabetic rats. PLoS One. 2014;9:e107220.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kokotkiewicz A, Luczkiewicz M, Pawlowska J, Luczkiewicz P, Sowinski P, Witkowski J, et al. Isolation of xanthone and benzophenone derivatives from Cyclopia genistoides (L.) Vent. (honeybush) and their pro-apoptotic activity on synoviocytes from patients with rheumatoid arthritis. Fitoterapia. 2013;90:199–208.

    Article  CAS  PubMed  Google Scholar 

  9. Luo Y, Fu C, Wang Z, Zhang Z, Wang H, Liu Y. Mangiferin attenuates contusive spinal cord injury in rats through the regulation of oxidative stress, inflammation and the Bcl-2 and Bax pathway. Mol Med Rep. 2015;12:7132–8.

    CAS  PubMed  Google Scholar 

  10. Huh J, Koh P, Seo B, Park Y, Baek Y, Lee J, et al. Mangiferin reduces the inhibition of chondrogenic differentiation by IL-1β in mesenchymal stem cells from subchondral bone and targets multiple aspects of the Smad and SOX9 pathways. Int J Mol Sci. 2014;15:16025–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Carvalho R, Pellizzon C, Justulin LJ, Felisbino S, Vilegas W, Bruni F, et al. Effect of mangiferin on the development of periodontal disease: involvement of lipoxin A4, anti-chemotaxic action in leukocyte rolling. Chem Biol Interact. 2009;179:344–50.

    Article  CAS  PubMed  Google Scholar 

  12. Jagetia G, Baliga M. Radioprotection by mangiferin in DBAxC57BL mice: a preliminary study. Phytomedicine. 2005;12:209–15.

    Article  CAS  PubMed  Google Scholar 

  13. Hou S, Wang F, Li Y, Li Y, Wang M, Sun D, et al. Pharmacokinetic study of mangiferin in human plasma after oral administration. Food Chem. 2012;132:289–94.

    Article  CAS  PubMed  Google Scholar 

  14. Xiao W, Hou J, Ma J, Yu B, Ren J, Jin W, et al. Mangiferin loaded magnetic PCEC microspheres: preparation, characterization and antitumor activity studies in vitro. Arch Pharm Res. 2014.

  15. Chang N, Lam C, Lin C, Chen W, Li C, Lin Y, et al. Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits. Osteoarthr Cartil. 2013;21:1613–22.

    Article  PubMed  Google Scholar 

  16. Yoon S, Park K, Kim M, Rhee J, Khang G, Lee H. Repair of diaphyseal bone defects with calcitriol-loaded PLGA scaffolds and marrow stromal cells. Tissue Eng. 2007;13:1125–33.

    Article  CAS  PubMed  Google Scholar 

  17. Lee H, Seo S, Chang H, Bang J, Joung Y, Son T, et al. Fabrication and characteristics of anti-inflammatory magnesium hydroxide incorporated PLGA scaffolds formed with various porogen materials. Macromol Res. 2014;22:210–8.

    Article  CAS  Google Scholar 

  18. Jeon O, Song S, Kang S, Putnam A, Kim B. Enhancement of ectopic bone formation by bone morphogenetic protein-2 released from a heparin-conjugated poly(L-lactic-co-glycolic acid) scaffold. Biomaterials. 2007;28:2763–71.

    Article  CAS  PubMed  Google Scholar 

  19. Song J, Xie J, Li C, Lu J, Meng Q, Yang Z, et al. Near infrared spectroscopic (NIRS) analysis of drug-loading rate and particle size of risperidone microspheres by improved chemometric model. Int J Pharm. 2014;472:296–303.

    Article  CAS  PubMed  Google Scholar 

  20. Hedberg E, Shih C, Lemoine J, Timmer M, Liebschner M, Jansen J, et al. In vitro degradation of porous poly(propylene fumarate)/poly(DL-lactic-co-glycolic acid) composite scaffolds. Biomaterials. 2005;26:3215–25.

    Article  CAS  PubMed  Google Scholar 

  21. Souza J, Carvalho J, Trevisan M, Paula R, Ricardo N, Feitosa J. Chitosan-coated pectin beads: characterization and in vitro release of mangiferin. food hydrocoll. 2009;23:2278–86.

    Article  Google Scholar 

  22. Kretlow J, Klouda L, Mikos A. Injectable matrices and scaffolds for drug delivery in tissue engineering. Adv Drug Deliv Rev. 2007;59:263–73.

    Article  CAS  PubMed  Google Scholar 

  23. Sharma A, Bharti S, Kumar R, Krishnamurthy B, Bhatia J, Kumari S, et al. Syzygium cumini ameliorates insulin resistance and β-cell dysfunction via modulation of PPAR, dyslipidemia, oxidative stress, and TNF-α in type 2 diabetic rats. J Pharmacol Sci. 2012;119:205–13.

    Article  CAS  PubMed  Google Scholar 

  24. Ravi N, Gupta G, Milbrandt T, Puleo D. Porous PLGA scaffolds for controlled release of naked and polyethyleneimine-complexed DNA. Biomed Mater. 2012;7:055007.

    Article  CAS  PubMed  Google Scholar 

  25. Liu M, Dai L, Shi H, Xiong S, Zhou C. In vitro evaluation of alginate/halloysite nanotube composite scaffolds for tissue engineering. Mater Sci Eng C Mater Biol Appl. 2015;49:700–12.

    Article  CAS  PubMed  Google Scholar 

  26. Hu Y, Ma S, Yang Z, Zhou W, Du Z, Huang J, et al. Facile fabrication of poly(L-lactic acid) microsphere-incorporated calcium alginate/hydroxyapatite porous scaffolds based on Pickering emulsion templates. Colloids Surf B: Biointerfaces. 2016;140:382–91.

    Article  CAS  PubMed  Google Scholar 

  27. Kim K, Dean D, Wallace J, Breithaupt R, Mikos A, Fisher J. The influence of stereolithographic scaffold architecture and composition on osteogenic signal expression with rat bone marrow stromal cells. Biomaterials. 2011;32:3750–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Watanabe K, Petro B, Shlimon A, Unterman T. Effect of periodontitis on insulin resistance and the onset of type 2 diabetes mellitus in Zucker diabetic fatty rats. J Periodontol. 2008;79:1208–16.

    Article  PubMed  Google Scholar 

  29. Li H, Wang Q, Xiao Y, Bao C, Li W. 25-Hydroxyvitamin D(3)-loaded PLA microspheres: in vitro characterization and application in diabetic periodontitis models. AAPS PharmSciTech. 2013;14:880–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lane J, Sandhu H. Current approaches to experimental bone grafting. Orthop Clin North Am. 1987;18:213–25.

    CAS  PubMed  Google Scholar 

  31. Zhu X, Cheng Y, Du L, Li Y, Zhang F, Guo H, et al. Mangiferin attenuates renal fibrosis through down-regulation of osteopontin in diabetic rats. Phytother Res. 2015;29:295–302.

    Article  CAS  PubMed  Google Scholar 

  32. Mandal B, Kundu S. Calcium alginate beads embedded in silk fibroin as 3D dual drug releasing scaffolds. Biomaterials. 2009;30:5170–7.

    Article  CAS  PubMed  Google Scholar 

  33. Wang J, Yang W, Xie H, Song Y, Li Y, Wang L. Ischemic stroke and repair: current trends in research and tissue engineering treatments. Regen Med Res. 2014;2:3.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wang Y, Liu X, Zhao J, Kong X, Shi R, Zhao X, et al. Degradable PLGA scaffolds with basic fibroblast growth factor: experimental studies in myocardial revascularization. Tex Heart Inst J. 2009;36:89–97.

    PubMed  PubMed Central  Google Scholar 

  35. Liu B, Cai S, Ma K, Xu Z, Dai X, Yang L, et al. Fabrication of a PLGA-collagen peripheral nerve scaffold and investigation of its sustained release property in vitro. J Mater Sci Mater Med. 2008;19:1127–32.

    Article  CAS  PubMed  Google Scholar 

  36. Oh S, Kang S, Lee J. Degradation behavior of hydrophilized PLGA scaffolds prepared by melt-molding particulate-leaching method: comparison with control hydrophobic one. J Mater Sci Mater Med. 2006;17:131–7.

    Article  CAS  PubMed  Google Scholar 

  37. Khaled K, Sarhan H, Ibrahim M, Ali A, Naguib Y. Prednisolone-loaded PLGA microspheres. In vitro characterization and in vivo application in adjuvant-induced arthritis in mice. AAPS PharmSciTech. 2010;11:859–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lee D, Kwon T, Kim K, Kwon S, Cho D, Jang S, et al. Anti-inflammatory drug releasing absorbable surgical sutures using poly(lactic-co-glycolic acid) particle carriers. Polym Bull. 2014;71:1933–46.

    Article  CAS  Google Scholar 

  39. Brochhausen C, Zehbe R, Watzer B, Halstenberg S, Gabler F, Schubert H, et al. Immobilization and controlled release of prostaglandin E2 from poly-L-lactide-co-glycolide microspheres. J Biomed Mater Res A. 2009;91:454–62.

    Article  PubMed  Google Scholar 

  40. Brownfield L, Weltman R. Ridge preservation with or without an osteoinductive allograft: a clinical, radiographic, micro-computed tomography, and histologic study evaluating dimensional changes and new bone formation of the alveolar ridge. J Periodontol. 2012;85:581–9.

    Article  Google Scholar 

  41. Jonnalagadda J, Rivero I, Dertien J. In vitro chondrocyte behavior on porous biodegradable poly(e-caprolactone)/polyglycolic acid scaffolds for articular chondrocyte adhesion and proliferation. J Biomater Sci Polym Ed. 2015;26:401–19.

    Article  CAS  PubMed  Google Scholar 

  42. Song J, Li J, Hou F, Wang X, Liu B. Mangiferin inhibits endoplasmic reticulum stress-associated thioredoxin-interacting protein/NLRP3 inflammasome activation with regulation of AMPK in endothelial cells. Metabolism. 2015;64:428–37.

    Article  CAS  PubMed  Google Scholar 

  43. Lee C, Lee Y. Preparation of porous biodegradable poly(lactide-co-glycolide)/hyaluronic acid blend scaffolds: characterization, in vitro cells culture and degradation behaviors. J Mater Sci Mater Med. 2006;17:1411–20.

    Article  CAS  PubMed  Google Scholar 

  44. Chang P, Chung M, Wang Y, Chien L, Lim J, Liang K, et al. Patterns of diabetic periodontal wound repair: a study using micro-computed tomography and immunohistochemistry. J Periodontol. 2012;83:644–52.

    Article  PubMed  Google Scholar 

  45. Graves D, Alblowi J, Paglia D, O’Connor J, Lin S. Impact of diabetes on fracture healing. J Exp Clin Med. 2011;3:3–8.

    Article  Google Scholar 

  46. Stolzing A, Sellers D, Llewelyn O, Scutt A. Diabetes induced changes in rat mesenchymal stem cells. Cells Tissues Organs. 2010;191:453–65.

    Article  CAS  PubMed  Google Scholar 

  47. Das A, Fishero B, Christophel J, Li C, Kohli N, Lin Y, et al. Poly(lactic-co-glycolide) polymer constructs cross-linked with human BMP-6 and VEGF protein significantly enhance rat mandible defect repair. Cell Tissue Res. 2015.

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81200794), Guangxi Natural Science Foundation (No. 2015GXNSFBA139140), Guangxi Scientific and Technologic Research Project of Colleges and Universities (No. KY2015YB060), and Youth Science Foundation of Guangxi Medical University (No. GXMUYSF2014017).

Author information

Authors and Affiliations

  1. Department of Prosthodontics, the Affiliated Hospital of Stomatology, Guangxi Medical University, 10 Shuangyong Road, Nanning, 530021, People’s Republic of China

    Hao Li & Hongbing Liao

  2. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 14 3rd Section S Renmin Road, Chengdu, 610041, People’s Republic of China

    Chongyun Bao, Yu Xiao & Qi Wang

Authors
  1. Hao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongbing Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chongyun Bao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hao Li or Chongyun Bao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, H., Liao, H., Bao, C. et al. Preparation and Evaluations of Mangiferin-Loaded PLGA Scaffolds for Alveolar Bone Repair Treatment Under the Diabetic Condition. AAPS PharmSciTech 18, 529–538 (2017). https://doi.org/10.1208/s12249-016-0536-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-016-0536-9

KEY WORDS

Search

Navigation