Search tips
Search criteria 


Logo of pharmscispringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSci. 2003 December; 5(4): 101–111.
Published online 2003 December 4. doi:  10.1208/ps050433
PMCID: PMC2750995

A photo-crosslinked poly(vinyl alcohol) hydrogel growth factor release vehicle for wound healing applications


The objective of this study was to develop and evaluate a hydrogel vehicle for sustained release of growth factors for wound healing applications. Hydrogels were fabricated using ultraviolet photo-crosslinking of acrylamide-functionalized nondegradable poly(vinyl alcohol) (PVA). Protein permeability was initially assessed using trypsin inhibitor (TI), a 21 000 MW model protein drug. TI permeability was altered by changing the solids content of the gel and by adding hydrophilic PVA fillers. As the PVA content increased from 10% to 20%, protein flux decreased, with no TI permeating through 20% PVA hydrogels. Further increase in model drug release was achieved by incorporating hydrophilic PVA fillers into the hydrogel. As filler molecular weight increased, TI flux increased. The mechanism for this is most likely an alteration in protein/gel interactions and transient variations in water content. The percent protein released was also altered by varying protein loading concentration. Release studies conducted using growth factor in vehicles with hydrophilic filler showed sustained release of platelet-derived growth factor (PDGF-β,β) for up to 3 days compared with less than 24 hours in the controls. In vitro bioactivity was demonstrated by doubling of normal human dermal fibroblas numbers when exposed to growth factor-loaded vehicle compared to control. The release vehicle developed in this study uses a rapid and simple fabrication method, and protein release can be tailored by modifying solid content, incorporating biocompatible hydrophilic fillers, and varying protein loading concentration.

Keywords: photo-crosslinkable hydrogel, poly(vinyl alcohol), platelet-derived growth factor, bioactivity, sustained release


1. Steed DL. Clinical evaluation of recombinant human plateletderived growth factor for the treatment of lower extremity diabetic ulcers. Diabetic Ulcer Study Group. J Vasc Surg. 1995;21(1):71–78. [PubMed]
2. Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III randomized placebo-controlled doubleblind study. Diabetes Care. 1998;21(5):822–827. doi: 10.2337/diacare.21.5.822. [PubMed] [Cross Ref]
3. Margolis DJ, Crombleholme T, Herlyn M. Clinical protocol: Phase I trial to evaluate the safety of H5.020CMV.PDGF-B for the treatment of a diabetic insensate foot ulcer. Wound Repair Regen. 2000;8(6):480–493. doi: 10.1046/j.1524-475x.2000.00480.x. [PubMed] [Cross Ref]
4. Arm DM, Tencer AF, Bain SD, Celino D. Effect of controlled release of platelet-derived growth factor from a porous hydroxyapatite implant on bone ingrowth. Biomaterials. 1996;17:703–709. doi: 10.1016/0142-9612(96)86740-8. [PubMed] [Cross Ref]
5. Kim HD, Valentini RF. Human osteoblast response in vitro to platelet-derived growth factor and transforming growth factor-β delivered from controlled-release polymer rods. Biomaterials. 1997;18(17):1175–1184. doi: 10.1016/S0142-9612(97)00049-5. [PubMed] [Cross Ref]
6. Lee JY, Nam SH, Im SY, et al. Enhanced bone formation by controlled growth factor delivery from chitosan-based biomaterials. J Control Release. 2002;78(1–3):187–197. doi: 10.1016/S0168-3659(01)00498-9. [PubMed] [Cross Ref]
7. Walsh WR, Kim HD, Jong YS, Valentini RF. Controlled release of platelet-derived growth factor using ethylene vinyl acetate copolymer (EVAc) coated on stainless-steel wires. Biomaterials. 1995;16(17):1319–1325. doi: 10.1016/0142-9612(95)91047-3. [PubMed] [Cross Ref]
8. Lee SJ, Park YJ, Park SN, et al. Molded porous poly(L-lactide) membranes for guided bone regeneration with enhanced effects by controlled growth factor release. J Biomed Mater Res. 2001;55(3):295–303. doi: 10.1002/1097-4636(20010605)55:3<295::AID-JBM1017>3.0.CO;2-W. [PubMed] [Cross Ref]
9. Park YJ, Ku Y, Chung CP, Lee SJ. Controlled release of platelet-derived growth factor from porous poly(L-lactide) membranes for guided tissue regeneration. J Control Release. 1998;51:201–211. doi: 10.1016/S0168-3659(97)00169-7. [PubMed] [Cross Ref]
10. Park YJ, Lee YM, Lee JY, Seol YJ, Chung CP, Lee SJ. Controlled release of platelet-derived growth factor-BB from chondroitin sulfate-chitosan sponge for guided bone regeneration. J Control Release. 2000;67(2–3):385–394. doi: 10.1016/S0168-3659(00)00232-7. [PubMed] [Cross Ref]
11. Park YJ, Lee YM, Park SN, Sheen SY, Chung CP, Lee SJ. Platelet derived growth factor releasing chitosan sponge for periodontal bone regeneration. Biomaterials. 2000;21:153–159. doi: 10.1016/S0142-9612(99)00143-X. [PubMed] [Cross Ref]
12. Zhou X, Zhao H. Topical treatment with growth factors for tympanic membrane perforations: progress towards clinical application. Acta Otolaryngol. 2002;122(6):586–599. doi: 10.1080/000164802320396259. [PubMed] [Cross Ref]
13. Richardson TM, Peters MC, Ennett AB, Mooney DJ. Polymeric system for dual growth factor delivery. Nat Biotechnol. 2001;19:1029–1034. doi: 10.1038/nbt1101-1029. [PubMed] [Cross Ref]
14. Peppas NA, Wright SL. Drug diffusion and binding in ionizable interpenetrating networks from poly(vinyl alcohol) and poly(acrylic acid) Eur J Pharm Biopharm. 1998;46:15–29. doi: 10.1016/S0939-6411(97)00113-6. [PubMed] [Cross Ref]
15. Hoffiman AS. Hydrogels for biomedical application. Adv. Drug Deliv Rev. 2002;43:3–12. doi: 10.1016/S0169-409X(01)00239-3. [Cross Ref]
16. Gupta P, Vermani K, Garg S. Hydrogels: from controlled release to pH-responsive drug delivery. Drug Discov Today. 2002;7(10):569–579. doi: 10.1016/S1359-6446(02)02255-9. [PubMed] [Cross Ref]
17. Gander B, Gurny R, Doelker E, Peppas NA. Effect of polymeric network structure on drug release from cross-linked poly(vinyl alcohol) micromatrices. Pharm Res. 1989;6(7):578–584. doi: 10.1023/A:1015949330425. [PubMed] [Cross Ref]
18. Hennink WE, Nostrum CF. Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev. 2002;54:13–36. doi: 10.1016/S0169-409X(01)00240-X. [PubMed] [Cross Ref]
19. Müller B. Photocrosslinked polymers. US patent 5 508 317. April, 16, 1996.
20. Huang X, Brazel CS. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release. 2001;73(2–3):121–136. doi: 10.1016/S0168-3659(01)00248-6. [PubMed] [Cross Ref]
21. Kök FN, Wilkins RM, Cain RB, Arica MY, Alaeddinoglu G, Hasirci V. Controlled release of aldicarb from lignin loaded ionotropic hydrogel microspheres. J Microencapsul. 1999;16:613–623. doi: 10.1080/026520499288807. [PubMed] [Cross Ref]
22. Krögel I, Bodmeier R. Development of a multifunctional matrix drug delivery system surrounded by an impermeable cylinder. J Control Release. 1999;61(1–2):43–50. doi: 10.1016/S0168-3659(99)00096-6. [PubMed] [Cross Ref]
23. Sako K, Sawada T, Nakashima H, Yokohama S, Sonobe T. Influence of water soluble fillers in hydroxypropylmethylcellulose matrices on in vitro and in vivo drug release. J Control Release. 2002;81(1–2):165–172. doi: 10.1016/S0168-3659(02)00067-6. [PubMed] [Cross Ref]

Articles from AAPS PharmSci are provided here courtesy of American Association of Pharmaceutical Scientists