title: Local delivery of basic fibroblast growth factor increases both angiogenesis and engraftment of hepatocytes in tissue-engineered polymer devices.
abstract: BACKGROUND
  We investigated heterotopic hepatocyte transplantation on biodegradable polymers as a potential treatment for end-stage liver disease. The primary problem has been insufficient engraftment of transplanted cells partly because of insufficient vascularization. Increasing vascularization through locally delivered angiogenic factors may increase angiogenesis and hepatocyte engraftment.
  
  
  METHODS
  We studied the effect of local delivery of basic fibroblast growth factor (bFGF) on angiogenesis and hepatocyte engraftment within tissue-engineered liver constructs. Poly-l-lactic acid discs were fabricated and coated with either a mixture of saline, sucralfate, and Hydron (control group) or bFGF, sucralfate, and Hydron (bFGF group). bFGF release from polymers in vitro was tested using an ELISA. Hepatocytes were isolated from Lewis rats, seeded on control (n=9) or bFGF (n=11) polymers, and implanted into the small bowel mesentery of syngeneic animals. Specimens were harvested after 2 weeks and analyzed for hepatocyte engraftment. Microvascular density was compared between control (n=6) and bFGF groups (n=5).
  
  
  RESULTS
  Three hundred twenty-three thousandths of a microgram of bFGF were incorporated per polymer. Greater than 99% of the bFGF was released into solution by 72 hr in vitro. Two weeks after implantation, microvascular density, as measured by capillaries per high-powered field (c/hpf), was significantly greater in the bFGF group (43.8 c/hpf), compared with the control group (30.5 c/hpf; P<0.005). Specimens from the bFGF group (mean engraftment, 61,355 microm2) showed a 2.5-fold increase in hepatocyte engraftment as compared with control (24,197 microm2; P<0.002).
  
  
  CONCLUSIONS
  The angiogenic growth factor bFGF can be incorporated into degradable polymers used as delivery devices for hepatocyte transplantation. Implantation of these devices increases angiogenesis into the device and increases hepatocyte engraftment.
authors.affiliation: Department of Surgery, University of California at San Francisco, San Francisco, California 94143-0570, USA.
authors.forename: Hanmin
authors.initials: H
authors.lastname: Lee
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cusick
authors.forename: Fiona
authors.initials: F
authors.lastname: Browne
authors.forename: Tae
authors.initials: T
authors.lastname: Ho Kim
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vacanti
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D022781:Hepatocytes / Q000637:transplantation*; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D016222:Fibroblast Growth Factor 2