title: Enzymatically degradable temperature-sensitive polypeptide as a new in-situ gelling biomaterial.
abstract: We are reporting a poly (ethylene glycol)-block-poly(alanine-co-phenyl alanine) (PEG-PAF) aqueous solution that undergoes sol-to-gel transition as the temperature increases. The sol-to-gel transition was observed at as low a concentration as 3.0-7.0 wt.%. Micellar aggregation accompanying small conformational changes of the peptide from random coils to beta-sheets is suggested as the sol-to-gel transition mechanism of the PEG-PAF aqueous solution. The PEG-PAF is stable in phosphate buffered saline, however, it degraded in the subcutaneous layer of rats. In vitro study showed that proteolytic enzymes such as cathepsin B, cathepsin C, and elastase that are present in the subcutaneous layer of the mammalian tissue might be responsible for the degradation of the polymer in rats. As a feasibility study of this material, a single shot of an aqueous insulin formulation (13.8 mg insulin/kg) showed a hypoglycemic effect over 18 days in rats. The current functional polypeptide may be very promising as an in-situ gelling system for tissue engineering, cell/stem cell therapy, and drug delivery.
authors.affiliation: Department of Chemistry and Nano Science, Ewha Womans University, Daehyun-Dong, Seodaemun-Ku, Seoul, 120-750, Republic of Korea.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Jeong
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Joo
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Bahk
authors.forename: Yun Young
authors.initials: YY
authors.lastname: Choi
authors.forename: Ho-Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Kim
authors.forename: Hwa Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Youn Soo
authors.initials: YS
authors.lastname: Sohn
authors.forename: Byeongmoon
authors.initials: B
authors.lastname: Jeong
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry*; D001673:Biodegradation, Environmental; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005240:Feasibility Studies; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage; D008823:Micelles; D015394:Molecular Structure; D008970:Molecular Weight; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D011487:Protein Conformation; D051381:Rats; D012996:Solutions; D050151:Subcutaneous Fat / Q000201:enzymology / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D005782:Gels; D007004:Hypoglycemic Agents; D007328:Insulin; D008823:Micelles; D010455:Peptides; D011108:Polymers; D012996:Solutions; D014867:Water; C019529:polyalanine; C012001:polyphenylalanine; D011092:Polyethylene Glycols