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Basic fibroblast growth factor for stimulation of bone formation in osteoinductive and conductive implants

Wang, Jian-Sheng LU (1996) In Acta Orthopaedica Scandinavica. Supplementum 269.
Abstract
Basic Fibroblast Growth Factor (bFGF) is one of the endogenous factors found in bone matrix. bFGF is a mitogen for many cell types, including osteoblasts and chondrocytes. It can stimulate angiogenesis and osteoblast gene expression. The purpose of this study was to investigate whether exogenous bFGF can stimulate the formation of bone in bone grafts and in a bone graft substitute. All experiments were performed in rats. In a model using demineralized bone matrix implants for bone induction, a dose of 15 ng bFGF per implant increased the number of chondrocytes and the amount of bone, whereas 1900 ng greatly inhibited cartilage and bone formation. These results are consistent with previous studies with this model, showing that a lower dose... (More)
Basic Fibroblast Growth Factor (bFGF) is one of the endogenous factors found in bone matrix. bFGF is a mitogen for many cell types, including osteoblasts and chondrocytes. It can stimulate angiogenesis and osteoblast gene expression. The purpose of this study was to investigate whether exogenous bFGF can stimulate the formation of bone in bone grafts and in a bone graft substitute. All experiments were performed in rats. In a model using demineralized bone matrix implants for bone induction, a dose of 15 ng bFGF per implant increased the number of chondrocytes and the amount of bone, whereas 1900 ng greatly inhibited cartilage and bone formation. These results are consistent with previous studies with this model, showing that a lower dose of bFGF increased bone calcium content and a higher dose reduced it. Thus, exogenous bFGF can stimulate proliferation during early phases of bone induction. A new device, the bone conduction chamber, was developed for the application of bFGF to bone conductive materials. This model made it possible to demonstrate a difference between the conductive properties of bone grafts and porous hydroxyapatite. bFGF in a hyaluronate carrier increased bone ingrowth into bone graft inside the chamber and showed a biphasic dose-response curve, so that 8-200 ng per implant (0.4-10 ng/mm3) increased bone ingrowth, but higher or lower doses had no effect. The same doses had the same effects in porous hydroxyapatite. In both bone grafts and porous hydroxyapatite, the highest dose still caused an increase in ingrowth of fibrous tissue. The effect on bone ingrowth was detected first 6 weeks after bFGF administration, regardless if this started at implantation or 2 weeks later, using an implanted minipump. Hyaluronate gel was effective as a slow-release carrier for bFGF. In conclusion, bFGF stimulates bone formation in bone implants, depending on dose and method for administration. (Less)
Abstract (Swedish)
Popular Abstract in Swedish

Basic Fibroblast Growth Factor (bFGF) är en av flera tillväxtfaktorer som finns lagrad i benvävnaden. bFGF framkallar celldelning och tillväxt hos många olika celltyper, däribland benceller (osteoblaster) och broskceller. bFGF kan stimulera till nybildning av blodkärl och även benvävnad. I denna avhandling undersökes om utifrån tillfört bFGF kan öka benbildning och vävnadsinväxt i olika benersättningsmaterial. I en försöksmodell används urkalkad benvävnad, som inplanteras i muskel på råtta. Härvid framkallas ny benbildning i inplantatet. En tillsats av 15 ng bFGF per inplantat ökade antalet broskceller och mängden ben, medan 1900 ng kraftigt minskade både brosk- och benbildning. Dessa resultat... (More)
Popular Abstract in Swedish

Basic Fibroblast Growth Factor (bFGF) är en av flera tillväxtfaktorer som finns lagrad i benvävnaden. bFGF framkallar celldelning och tillväxt hos många olika celltyper, däribland benceller (osteoblaster) och broskceller. bFGF kan stimulera till nybildning av blodkärl och även benvävnad. I denna avhandling undersökes om utifrån tillfört bFGF kan öka benbildning och vävnadsinväxt i olika benersättningsmaterial. I en försöksmodell används urkalkad benvävnad, som inplanteras i muskel på råtta. Härvid framkallas ny benbildning i inplantatet. En tillsats av 15 ng bFGF per inplantat ökade antalet broskceller och mängden ben, medan 1900 ng kraftigt minskade både brosk- och benbildning. Dessa resultat överensstämmer med tidigare studier med samma doser i denna modell, varvid dock endast mängden kalcium mättes och användes som mått på benmängd. Den nya studien visar att bFGF ökar utbytet av beninduktion genom att stimulera celltillväxten i tidiga stadier. En benkonduktionskammare utvecklades för att mäta olika porösa materials förmåga att leda växande vävnad in i ett hålrum. Kammaren opererades in i råttans underben. Med denna modell kunde man påvisa en skillnad i vävnadsledande (konduktiva) egenskaper mellan porös hydroxylapatit och poröst ben (fryst, urfettad bengraft). Bengraften var bättre. När bFGF i en hyaluronan-gel tillsattes bengraften före inplantationen ökade beninväxten om doser mellan 0,4 och 10 ng/mm3 inplantat användes. Högre och lägre doser inverkade inte på beninväxten. Samma doser hade liknande effekter i porös hydroxylapatit. I både bengraft och hydroxylapatit ledde de högsta doserna till en ökad inväxt av fibrös vävnad, med oförändrad beninväxt. Ökad beninväxt blev synlig först 6 veckor efter att bFGF tillförts, detta oavsett om det tillfördes vid inplantationen eller 2 veckor senare med hjälp av en inopererad minipump, som anslutits till kammaren. Hyaluronan-gel visade sig vara en effektiv bärare för bFGF, men det var möjligt att få positiva effekter utan bärare genom att kraftigt höja doserna. Sammanfattningsvis visar avhandlingen att bFGF kan öka benbildningen i olika benersättningsmaterial, beroende på dos och tillförselsätt. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Prof Nilsson, Olle, Dept. of Orthopedics, Uppsala
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Surgery, Biofysik, Biophysics, bone ingrowth, titanium chamber, hyaluronic acid, porous hydroxyapatite, bone graft, bFGF, demineralized bone matrix, orthopaedics, traumatology, Kirurgi, ortopedi, traumatologi
in
Acta Orthopaedica Scandinavica. Supplementum
volume
269
pages
33 pages
publisher
Scandinavian University Press
defense location
Föreläsningssal 3, Centralblocket
defense date
1996-03-28 10:15:00
external identifiers
  • other:ISRN: LUMEDW/MEOL 1046(1-40)1996
  • scopus:0030117109
ISSN
0300-8827
ISBN
91-628-1901-1
language
English
LU publication?
yes
id
30d599a7-ee6d-48c0-915a-5af60beb83cc (old id 28245)
date added to LUP
2016-04-01 16:16:41
date last changed
2022-04-07 07:03:56
@phdthesis{30d599a7-ee6d-48c0-915a-5af60beb83cc,
  abstract     = {{Basic Fibroblast Growth Factor (bFGF) is one of the endogenous factors found in bone matrix. bFGF is a mitogen for many cell types, including osteoblasts and chondrocytes. It can stimulate angiogenesis and osteoblast gene expression. The purpose of this study was to investigate whether exogenous bFGF can stimulate the formation of bone in bone grafts and in a bone graft substitute. All experiments were performed in rats. In a model using demineralized bone matrix implants for bone induction, a dose of 15 ng bFGF per implant increased the number of chondrocytes and the amount of bone, whereas 1900 ng greatly inhibited cartilage and bone formation. These results are consistent with previous studies with this model, showing that a lower dose of bFGF increased bone calcium content and a higher dose reduced it. Thus, exogenous bFGF can stimulate proliferation during early phases of bone induction. A new device, the bone conduction chamber, was developed for the application of bFGF to bone conductive materials. This model made it possible to demonstrate a difference between the conductive properties of bone grafts and porous hydroxyapatite. bFGF in a hyaluronate carrier increased bone ingrowth into bone graft inside the chamber and showed a biphasic dose-response curve, so that 8-200 ng per implant (0.4-10 ng/mm3) increased bone ingrowth, but higher or lower doses had no effect. The same doses had the same effects in porous hydroxyapatite. In both bone grafts and porous hydroxyapatite, the highest dose still caused an increase in ingrowth of fibrous tissue. The effect on bone ingrowth was detected first 6 weeks after bFGF administration, regardless if this started at implantation or 2 weeks later, using an implanted minipump. Hyaluronate gel was effective as a slow-release carrier for bFGF. In conclusion, bFGF stimulates bone formation in bone implants, depending on dose and method for administration.}},
  author       = {{Wang, Jian-Sheng}},
  isbn         = {{91-628-1901-1}},
  issn         = {{0300-8827}},
  keywords     = {{Surgery; Biofysik; Biophysics; bone ingrowth; titanium chamber; hyaluronic acid; porous hydroxyapatite; bone graft; bFGF; demineralized bone matrix; orthopaedics; traumatology; Kirurgi; ortopedi; traumatologi}},
  language     = {{eng}},
  publisher    = {{Scandinavian University Press}},
  school       = {{Lund University}},
  series       = {{Acta Orthopaedica Scandinavica. Supplementum}},
  title        = {{Basic fibroblast growth factor for stimulation of bone formation in osteoinductive and conductive implants}},
  volume       = {{269}},
  year         = {{1996}},
}