Preclinical promise of becaplermin (rhPDGF-BB) in wound healing.
Advances in molecular biology have made possible the production of highly purified recombinant human proteins, and recombinant human growth factors have emerged as potential therapeutic wound healing agents. Becaplermin (recombinant human platelet-derived growth factor-BB [rhPDGF-BB]) quickly emerged as one of the leading candidates for clinical trials. Before the expected therapeutic potential of rhPDGF-BB and other growth factors could be realized, a number of concerns had to be addressed (eg, would growth factors show effects in normal animals, what parameters of wound healing would be affected, and would quality of healed wounds be normal?). In animal models, rhPDGF-BB demonstrated wound healing activity, predominantly by enhancing the formation of granulation tissue, but it was not known whether this effect on granulation tissue would translate into enhanced healing of chronic skin ulcers in humans. The objective of this article is to review how the study of rhPDGF-BB in animal wound healing models has assisted in addressing the potential clinical utility of rhPDGF-BB. Results of animal studies are summarized, and the advantages and limitations of the animal models are discussed.
The R.W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869, USA.
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LeGrand
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D000077214:Becaplermin; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology / Q000627:therapeutic use*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012883:Skin Ulcer / Q000188:drug therapy* / Q000473:pathology; D013552:Swine; D014945:Wound Healing
D000925:Anticoagulants; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin