Browse > Article

PLGA Microspheres in Hyaluronic Acid Gel as a Potential Bulking Agent for Urologic and Dermatologic Injection Therapies  

KANG SUN-WOONG (Department of Chemical Engineering, Hanyang University)
CHO EUI RI (Department of Chemical Engineering, Hanyang University)
KIM BYUNG-SOO (Department of Chemical Engineering, Hanyang University)
Publication Information
Journal of Microbiology and Biotechnology / v.15, no.3, 2005 , pp. 510-518 More about this Journal
Abstract
In this study, we investigated whether PLGA microspheres in combination with hyaluronic acid (HA) gel have appropriate properties as a bulking agent for urologic injection therapies and whether the implantation of PLGA microspheres and HA gel induces angiogenesis in the newly formed tissues. In order to investigate whether this bulking agent is injectable, this material was injected through 24-gauge needles into the subcutaneous dorsum of the mouse. The bulking agent was easily injected without needle obstruction. Histological analyses of the hybrid tissues at 2 weeks showed that host cells at the surrounding tissues migrated into the spaces between the implanted PLGA microspheres and formed tissue-like structures. An inflammatory response to the implants was mild at 2 weeks and diminished at 8 weeks. Importantly, extensive ingrowth of blood vessels was observed in the hybrid tissues formed by the injection of PLGA microspheres and HA, whereas blood vessels rarely formed in the hybrid tissues formed by the injection of PLGA microspheres only. The implant volume was conserved for almost the entire implantation period. Histological analyses of the distant organs of the bulking agent-implanted animals, such as the lungs, liver, heart, brain, kidney, and spleen, showed no evidence of the injected microsphere migration. These results show that PLGA microspheres in combination with HA possess the appropriate characteristics for a bulking agent for urologic injection therapies and induce extensive blood vessel formation in the hybrid tissues.
Keywords
Angiogenesis; bulking agent; hyaluronic acid; injection therapy; poly(lactic-co-glycolic acid) microsphere;
Citations & Related Records

Times Cited By Web Of Science : 10  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Al-Hunayan, A. A., E. O. Kehinde, M. A. Elsalam, and R. S. Al-Mukhtar. 2002. Outcome of endoscopic treatment for vesicoureteral reflux in children using polydimethylsiloxane. J. Urol. 168: 2181-2183   DOI   ScienceOn
2 Biswal, D. R. and R. P. Singh. 2004. Characterisation of carboxymethyl cellulose and poly-acrylamide graft copolymer. Carbohydrate Polymers 57: 379-387   DOI   ScienceOn
3 Claes, H., D. Stroobants, J. Van Meerbeek, E. Verbeken, D. Knockaert, and L. Baert. 1989. Pulmonary migration following periurethral polytetrafluoroethylene injection for urinary incontinence. J. Urol. 142: 821-822   DOI   PUBMED
4 Dmochowski, R. R. and R. A. Appell. 2000. Injectable agents in the treatment of stress urinary incontinence in women: Where are we now? Urology 56: 32-40   DOI   ScienceOn
5 Food and Drug Administration (USA) website. www.fda.gov
6 Kim, B. S., C. E. Baez, and A. Atala. 2000. Biomaterials for tissue engineering. World J. Urol. 18: 2-9   DOI   ScienceOn
7 Lees, V C., T. P. D. Fan, and D. C. West. 1995. Angiogenesis in a delayed revascularization model is accelerated by angiogenic oligosaccharides of hyaluronan. Lab. Invest. 73: 259-266
8 Lemperle, G., N. Hazan-Gauthier, and M. Lemperle. 1995. PMMA microspheres (Artecoll) for skin and soft-tissue augmentation. Part II: Clinical investigations. Plast. Reconstr. Surg. 96: 627-634   DOI   PUBMED   ScienceOn
9 Leonard, M. P., D. A. Canning, C. A. Peters, J. P. Gearhart, and R. D. Jeffs. 1991. Endoscopic injection of glutaraldehyde cross-linked bovine dermal collagen for correction of vesicoureteral reflux. J. Urol. 145: 115-119   DOI   PUBMED
10 Wang, J., T. T. Shih, K. J. Chang, and Y. W. Li. 2002. Silicone migration fram silicone-injected breasts: Magnetic resonance images. Ann. Plast. Surg. 48: 617-621   DOI   ScienceOn
11 West, D. C., I. N. Hampson, F. Arnold, and S. Kumar. 1985. Angiogenesis induced by degradation products of hyaluronic acid. Science 228: 1324-1326   DOI   PUBMED
12 West, D. C. and S. Kumar. 1989. The effects of hyaluronate and it oligosaccharides on endothelial cell proliferation and monolayer integrity. Exp. Cell Res. 183: 179-196   DOI   ScienceOn
13 Sattar, A., P. Rooney, S. Kumar, D. Pye, D. C. West, I. Scott, and P. Ledger. 1994. Application of angiogenic oligosaccharides of hyaluronan increase bloodvessel numbers in skin. J. Invest. Dermatol. 103: 573-579
14 Manna, F., M. Dentini, P. Desideri, O. De Pita, E. Mortilla, and B. Maras. 1999. Comparative chemical evaluation of two commercially available derivatives of hyaluronic acid (Hylaform${\circledR}$ from rooster combs and Restylane${\circledR}$ from Streptococcus) u.sed for soft tissue augmentation. J. Eur. Acad. Dermatol. Venereol. 13: 183-192   DOI   PUBMED
15 Newman, K. D. and M. W. McBurney. 2004. Poly(D,L lactic-co-glycolic acid) microspheres as biodegradable microcarriers for pluripotent stem cells. Biomaterials 25: 57-63
16 Montesano, R., S. Kumar, L. Orci, and M. S. Pepper. 1996. Synergistic effect of hyaluronan oligosaccharides and vascular endothelial growth factor on angiogenesis in vitro. Lab. Invest. 75: 249-262
17 Savani, R. C., G. Cao, P. M. Pooler, A. Zaman, Z. Zhou, and H. M. DeLisser. 2001. Differential involvement of the hyaluranan (HA) receptors CD44 and receptor for HA-mediated motility in endothelial cell function and angiogenesis. J. Biol. Chem. 28: 36770-36778
18 Lee, P. E., R. C. Kung, and H. P. Drutz. 2001. Periurethral autologous fat injection as treatment for female stress urinary incontinence: A randomized double-blind controlled trial. J. Urol. 165: 153-158   DOI   ScienceOn
19 Malizia, A. A., H. M. Reiman, R. P. Myers, J. R. Sande, S. S. Barham, R. C. Benson, M. K. Dewanjee, and W. J. Utz. 1984. Migration and granulomatous reaction after periurethral injection of Polytef(Teflon). JAMA 251: 3277 -3281   DOI   ScienceOn
20 Oldham, J. B., L. Lu, X. Zhu, B. D. Porter, T. E. Hefferan, D. R. Larson, B. L. Currier, A. G. Mikos, and M. J. Yaszemski. 2000. Biological activity of rhBMP-2 released from PLGA microspheres. J. Biomech. Eng. 122: 289-292   DOI   ScienceOn
21 Trackman, B. A. and G. E. Leach. 1995. Surgical treatment of intrinsic urethral dysfunction: Injectables (fat). Urol. Clin. North Am. 22: 665-671   PUBMED
22 Kerrebroeck, P. V, F. T. Meulen, E. Farrelly, G. Larsson, L. Edwall, and A. Fianu-Jonasson. 2003. Treatment of stress urinary incontinence: Recent developments in the role of urethral injection. Urol. Res. 30: 356-362   PUBMED
23 Requena, C., M. J. Izquierdo, M. Navarro, A. Martinez, J. J. Vilata, R. Botella, J. Amorrortu, V. Sabater, A. Aliaga, and L. Requena. 2001. Adverse reactions to injectable aesthetic microimplants. Am. J. Dermatopathol. 23: 197-202   DOI   ScienceOn
24 Aragona, F., L. D'Urso, E. Scremin, R. Salmaso, and G. P. Glazel. 1997. Polytetrafluoroethylene giant granuloma and adenopathy: Long-term complications following subureteral polytetrafluoroethylene injection for the treatment of vesicoureteral reflux in children. J. Urol. 158: 1539-1542   DOI   ScienceOn
25 Colton, C. K. 1995. Implantable biohybrid artificial organs. Cell Transplant. 4: 415-436   DOI   PUBMED   ScienceOn
26 DeLustro, F., S. T. Smith, J. Sundsmo, G. Salem, S. Kincaid, and L. Ellingsworth. 1987. Reaction to injectable collagen: Results in animal models and clinical use. Plast. Reconstr. Surg. 79: 581-594   DOI   PUBMED   ScienceOn
27 Leonard, M. P., A. Deeter, K. Hills, and L. W. Mix. 1998. Endoscopic subureteral collagen injection: Are immunological concerns justified? J. Urol. 160: 10 12-1016   DOI   ScienceOn
28 Kim, D. I., H. J. Park, H. S. Eo, S. W. Suh, J. H. Hong, M. J. Lee, J. S. Kim, I. S. Jang, and B. S. Kim. 2004. Comparative study of seeding and culture methods to vascular smooth muscle cells on biodegradable scaffold. J. Microbiol. Biotechnol. 14: 707 - 714
29 Achauer, B. M. 1983. A serious complication following medical-grade silicone injection of the face. Plast. Recanstr. Surg. 71: 251-254   DOI   ScienceOn
30 Herz, D., A. Hafez, D. Bagli, G. Capolicchio, G. McLorie, and A. Khoury. 2001. Efficacy of endoscopic subureteral polydimethylsiloxane injection for treatment ofvesicoureteral reflux in chirdren: A North American clinical report. J. Urol. 166: 1880-1886   DOI   ScienceOn
31 Capozza, N., M. Patricolo, A. Lais, E. Matarazzo, and P. Caione. 2001. Endoscopic treatment of vesico-ureteral reflux: Twelve years' experience. Urol. Int. 67: 228-231   DOI   ScienceOn
32 Aboutaleb, H., S. Bolduc, A. E. Khoury, J. Upadhyay, D. J. Bagli, and W. Farhat. 2003. Polydimethylsiloxane injection versus open surgery for the treatment of vesicoureteral reflux in complete duplex system. J. Urol. 170: 1563-1565   DOI   PUBMED   ScienceOn
33 Griffey, S., N. D. Schwade, and C. G. Wright. 2001. Particulate dermal matrix as an injectable soft tissue replacement material. J. Biomed. Mater. Res. 58: 10-15   DOI   ScienceOn
34 Kim, B. S., S. I. Jeong, S. W. Cho, J. Nikolovski, D. J. Mooney, S. H. Lee, O. Jeon, T. W. Kim, S. H. Lim, Y. S. Hong, C. Y. Choi, Y. M. Lee, S. H. Kim, and Y. H. Kim. 2003. Tissue engineering of smooth muscle under a mechanically dynamic condition. J. Microbiol. Biotechnol. 13: 841-845
35 Bent, A. E., J. Foote, S. Siegel, G. Faerber, R. Chao, and E. A. Gormley. 2001. Collagen implant for treating stress urinary incontinence in women with urethral hypermobility. J. Urol. 166: 1354-1357   DOI   ScienceOn
36 Conrad, K. and M. R. MacDonald. 1996. Wide polytef (Gore-Tex) implants in lip augmentation and nasolabial groove correction. Arch. Otolaryngol. Head Neck Surg. 122: 664-670   DOI   PUBMED   ScienceOn
37 Inoue, K., T. Nakamoto, A. Usui, and T. Usui. 2000. Endoscopic sub ureteral glutaraldehyde cross-linked collagen injection for the treatment of secondary vesicoureteral reflux: Comparison with primary vesicoureteral reflux in adults. J. Urol. 164: 336-339   DOI   ScienceOn
38 Kershen, R. T. and A. Atala. 1999. New advances in injectable therapies for the treatment of incontinence and vesicoureteral reflux. Urol. Clin. North Am. 26: 81-94   DOI   PUBMED   ScienceOn
39 Lemperle, G., V. Morhenn, and U. Charrier. 2003. Human histology and persistence of various injectable filler substances for soft tissue augmentation. Aesth. Plast. Surg. 27: 354-366   DOI   ScienceOn
40 Oswald, J., M. Riccabona, L. Lusuardi, G. Bartsch, and C. Radmayr. 2002. Prospective comparison and 1-year followup of a single endoscopic subureteral polydimethylsiloxane versus dextranomer/hyaluronic acid copolymer injection for treatment of vesicoureteral reflux in children. Urology 60: 894-898   DOI   ScienceOn
41 Morhenn, V. B., G. Lemperle, and R. L. Gallo. 2002. Phagocytosis of different particulate dermal filler substances by human macrophages and skin cells. Dermatol. Surg. 28: 484-490   DOI   ScienceOn
42 Joyner, B. D. and A. Atala; 1997. Endoscopic substances for the treatment of vesicoureteral reflux. Urology 50: 489-494   DOI   ScienceOn
43 Sattar, A., S. Kumar, and D. C. West. 1992. Does hyaluronan have a role in endothelial cell proliferation in the synovium? Semin. Arthritis Rheum. 22: 37-43   DOI   ScienceOn
44 Aaronson, I. A., R. A. Rames, W. B. Greene, L. G. Walsh, U. A. Hasal, and P. D. Garen. 1993. Endoscopic treatment of reflux: Migration of polytetrafluoroethylene into the lungs and brain. Eur. Urol. 23: 394-399   DOI   PUBMED
45 Hu, M., E. E. Sabelman, Y. Cao, J. Chang, and V. R. Hentz. 2003. Three-dimensional hyaluronic acid grafts promote healing and reduce scar formation in skin incision wounds. J. Biomed. Mater. Res. 67: 586-592
46 Knudson, C. B. and W. Knudson. 2001. Cartilage proteoglycans. Semin. Cell. Dev. Biol. 12: 69-78   DOI   ScienceOn
47 Peattie, R. A., A. P. Nayate, M. A. Firpo, J. Shelby, R. J. Fisher, and G. D. Prestwich. 2004. Stimulation of in vivo angiogenesis by cytokine-loaded hyaluronic acid hydrogel implants. Biomaterials 25: 2789-2798   DOI   ScienceOn
48 Cohen, S., T. Yoshioka, M. Lucarelli, L. H. Hwang, and R. Langer. 1991. Controlled delivery systems for proteins based on poly(lactic-co-glycolic acid) microspheres. Pharm. Res. 8: 713   DOI   PUBMED   ScienceOn
49 Yanagihara, M., T. Fujii, N. Wakamatu, H. Ishizaki, T. Takehara, and K. Nawate. 2000. Silicone granuloma on the entry points of acupuncture, venepuncture and surgical needles. J. Cutan. Pathol. 27: 301-305   DOI   ScienceOn
50 Sclafani, A. P., T. Romo 3rd, A. Parker, S. A. McCormick, R. Cocker, and A. Jacono. 2002. Homologous collagen dispersion (dermalogen) as a dermal filler: Persistence and histology compared with bovine collagen. Ann. Plast. Surg. 49: 181-188   DOI   ScienceOn
51 Pollack, S. V. 1999. Some new injectable dermal filler materials: Hylaform, Restylane, and Artecoll. J. Cutan. Med. Surg. 3: 27-35
52 O'Donnell, B. and P. Puri. 1984. Treatment of vesicoureteric reflux by endoscopic injection of Teflon. Br. Med. J. 289: 79   DOI
53 Thomson, R. C., M. C. Wake, M. J. Yaszemski, and A. G. Mikos. 1995. Biodegradable polymer scaffolds to regenerate organs. Adv. Polym. Sci. 122: 245-274
54 Kang, S. W., O. Jeon, and B. S. Kim. 2005. Poly(lactic-coglycolic acid) microspheres as an injectable scaffold for cartilage tissue engineering. Tissue Engineering (in press)
55 Lemperle, G., N. Gauthier-Hazan, and M. Lemperle. 1998. PMMA-microspheres (Artecoll) for long-lasting correction of wrinkles: Refinements and statistical results. Aesth. Plast. Surg. 22: 356-365   DOI   ScienceOn
56 Politano, V. A. 1982. Periurethral polytetrafluoroethylene injection for urinary incontinence. J. Urol. 127: 439-442   DOI   PUBMED
57 Cho, E. R., S. W. Kang, and B. S. Kim. 2005. Poly(lactic-coglycolic acid) microspheres as a potential bulking agent for urological injection therapy; preliminary results. J. Biomed. Mater. Res. 72B: 166-172   DOI