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Tissue reactions to biomaterials

Rosengren, Agneta LU (1997)
Abstract (Swedish)
Popular Abstract in Swedish

Det blir allt vanligare att man ersätter förlorade och skadade kroppsdelar med ett biomaterial (vanligtvis ett metall eller polymer implantat). Exempel på vanliga användningsområden är; suturer, kärl, hjärtklaffar, pacemakers, katetrar, ledproteser, fixationsskruvar för skelett och konstgjorda tänder samt kapslar för långsam frisättning av medicin. Trots det rutinmässiga användandet av biomaterial vet vi idag relativt lite om de mekanismer som avgör om ett implantat kommer att accepteras och integreras eller om det istället kapslas in och avstöts. Den tidigare biomaterialforskningen har framförallt varit av klinisk tillämpad karaktär. Experimentella studier har dock visat att det biologiska... (More)
Popular Abstract in Swedish

Det blir allt vanligare att man ersätter förlorade och skadade kroppsdelar med ett biomaterial (vanligtvis ett metall eller polymer implantat). Exempel på vanliga användningsområden är; suturer, kärl, hjärtklaffar, pacemakers, katetrar, ledproteser, fixationsskruvar för skelett och konstgjorda tänder samt kapslar för långsam frisättning av medicin. Trots det rutinmässiga användandet av biomaterial vet vi idag relativt lite om de mekanismer som avgör om ett implantat kommer att accepteras och integreras eller om det istället kapslas in och avstöts. Den tidigare biomaterialforskningen har framförallt varit av klinisk tillämpad karaktär. Experimentella studier har dock visat att det biologiska svaret är beroende av implantatets egenskaper. Tidigare forskning har visat att cellreaktioner är beroende av vilka proteiner implantatytan täcks av. Detta tillsammans med vetskapen om att implantatytor som exponeras för en biologisk omgivning snabbt täcks av dess proteiner, har skapat hypotesen att de cellreaktioner som implantatet alstrar till stor del styrs av de proteiner som initialt omger implantatet.



Denna avhandling har haft som huvudsakligt mål att studera vävnadsreaktioner kring olika typer av biomaterial.



Vi har utvecklat en teknik för att identifiera och lokalisera implantatnära proteiner. Denna teknik, som är användbar för både ljus- och elektronmikroskopi, har tillåtit oss att jämföra distributionen av vissa valda proteiner (albumin, fibrinogen, fibronektin, IgG och kollagen) runt två implantatmaterial, titan och polytetrafluoroethylen (PTFE), i bukväggen hos råtta. De individuella proteinerna var olikt distribuerade och denna distribution förändrades under uppföljningsperioden (1-12 veckor). För vissa proteiner var distributionsmönstret olika vid de två materialen.



För att utvärdera om implantationslokal, materialtyp och ytstruktur har någon betydelse för vilka celler som ansamlas, använde vi antikroppar riktade mot två olika typer av makrofager (vilka är viktiga inflammationsceller). Med hjälp av ljusmikroskopi räknades makrofager samt övriga celler. Vi mätte också tjockleken på den inflammatoriska kapsel som bildats runt implantatet. Alla implantat sattes i råttans bukvägg.



Lokalisationens betydelse undersöktes med titanimplantat som penetrerade, respektive inte penetrerade bukhinnan hos råtta. Totala antalet celler och makrofager samt kapseltjocklek jämfördes under 3-30 dagar. De penetrerande implantaten orsakade ett mer uttalat inflammationssvar, men först efter 30 dagars implantation.



PTFE och titanimplantat, vilka har vitt skilda materialegenskaper, jämfördes med avseende på cellantal och kapseltjocklek under 1-12 veckor. Runt PTFE fanns totalt fler celler och en kraftigare kapsel först efter 12 veckors implantation. Emellertid fann vi inga signifikanta skillnader i makrofagantalet mellan de två typerna av material.



Variationer i ytstruktur hos implantat av polyeten orsakade små men signifikanta skillnader i vävnadssvaret under uppföljningsperioden som var 1-12 veckor. Den släta ytan omgavs av den tjockaste kapseln vid alla tidpunkter, och efter 1 veckas implantation var också makrofagantalet och det totala antalet celler större än vid de strukturerade ytorna.



Sammanfattningsvis, variationer av implantatets lokalisation, materialegenskaper och ytstruktur gav signifikanta skillnader i det biologiska svaret, men först efter en relativt lång implantationstid. (Less)
Abstract
The biological response to different implanted biomaterials vary. The relative importance of factors in the material and host for this variation are at present incompletely known. The variation in the cellular response to specific proteins and the rapid adsorption of proteins to surfaces exposed to biological environments has created the hypothesis that the cellular interactions with biomaterials are influenced by the accumulated plasma proteins. These initial reactions have been suggested to determine the subsequent wound healing process and the long term stability of an implant.



The main purpose of the present thesis was to study the distribution of selected proteins and to quantify the macrophage subpopulations, in... (More)
The biological response to different implanted biomaterials vary. The relative importance of factors in the material and host for this variation are at present incompletely known. The variation in the cellular response to specific proteins and the rapid adsorption of proteins to surfaces exposed to biological environments has created the hypothesis that the cellular interactions with biomaterials are influenced by the accumulated plasma proteins. These initial reactions have been suggested to determine the subsequent wound healing process and the long term stability of an implant.



The main purpose of the present thesis was to study the distribution of selected proteins and to quantify the macrophage subpopulations, in the soft tissue adjacent to implants with different characteristics and at different localization.



A technique was developed for light and electron microscopical studies on the localization of accumulated proteins in the relatively inaccessible zone between implant and soft tissue. A procedure including mild chemical fixation, cryosubstitution and electrochemical removal of the metallic implant allowed immunohistochemical localization of selected proteins.



Implants of commercially pure (c.p.) titanium and polytetrafluoroethylene (PTFE) were inserted in rat abdominal wall for 1-12 weeks. Differences in the distribution pattern of the individual proteins (albumin, fibrinogen, fibronectin, IgG and collagen I) were revealed. The distribution also varied over time and differed to some extent between the two materials.



Macrophage-specific antibodies were used for identification of newly recruited macrophages (ED1) and of mature tissue macrophages (ED2) in the soft tissue adjacent to titanium implants which penetrated or did not penetrate, respectively, the peritoneal membrane of rat for 3-30 days. The penetrating implants induced a more pronounced inflammatory response at 30 days but not at earlier time points.



PTFE and c.p. titanium, which have widely different material properties, were compared with respect to the number of macrophage subpopulations and total cells during a 12 weeks follow-up period. PTFE induced a larger accumulation of cells and a thicker capsule formation at 12 weeks insertion. However, no significant differences were seen in the macrophage subset response between the two implants.



Variation in surface topography on polyethylene implants induced small but significant differences in the soft tissue response when examined after 1-12 weeks. The smoother surface induced the thickest capsule formation at all time points, and at 1 week it also recruited the largest number of macrophages and total cells as compared to the coarser surfaces.



In summary, significant differences in the biological response to implanted biomaterials due to localization, material characteristics and surface topography were seen, particularly after relatively long implantation times. (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Doc Johansson, Carina, Avd. för Handikappforskning, Medicinaregatan 8B, 413 90 Göteborg
organization
publishing date
type
Thesis
publication status
published
subject
keywords
cytochemistry, Histology, Macrophages, Cryosubstitution, Proteins, Immunohistochemistry, Titanium, Implants, PTFE, histochemistry, tissue culture, Histologi, cytokemi, histokemi, vävnadskultur
pages
121 pages
publisher
Inst. fysiologi och neurovetenskap, avd. neuroendokrin cellbiologi, EA-blocket, 5:e vån., Universitetssjukhuset, 221 85 Lund,
defense location
Segerfalksalen, Wallenberg Neurocenter, Sölvegatan 17, Lund
defense date
1997-09-25 09:15
external identifiers
  • other:ISRN: LUMEDW/MEFN-10-SE
ISBN
91-628-2607-7
language
English
LU publication?
yes
id
6f5670cf-a9c3-49f9-9dfb-984f5e22f926 (old id 29466)
date added to LUP
2007-06-12 16:11:30
date last changed
2016-09-19 08:45:13
@phdthesis{6f5670cf-a9c3-49f9-9dfb-984f5e22f926,
  abstract     = {The biological response to different implanted biomaterials vary. The relative importance of factors in the material and host for this variation are at present incompletely known. The variation in the cellular response to specific proteins and the rapid adsorption of proteins to surfaces exposed to biological environments has created the hypothesis that the cellular interactions with biomaterials are influenced by the accumulated plasma proteins. These initial reactions have been suggested to determine the subsequent wound healing process and the long term stability of an implant.<br/><br>
<br/><br>
The main purpose of the present thesis was to study the distribution of selected proteins and to quantify the macrophage subpopulations, in the soft tissue adjacent to implants with different characteristics and at different localization.<br/><br>
<br/><br>
A technique was developed for light and electron microscopical studies on the localization of accumulated proteins in the relatively inaccessible zone between implant and soft tissue. A procedure including mild chemical fixation, cryosubstitution and electrochemical removal of the metallic implant allowed immunohistochemical localization of selected proteins.<br/><br>
<br/><br>
Implants of commercially pure (c.p.) titanium and polytetrafluoroethylene (PTFE) were inserted in rat abdominal wall for 1-12 weeks. Differences in the distribution pattern of the individual proteins (albumin, fibrinogen, fibronectin, IgG and collagen I) were revealed. The distribution also varied over time and differed to some extent between the two materials.<br/><br>
<br/><br>
Macrophage-specific antibodies were used for identification of newly recruited macrophages (ED1) and of mature tissue macrophages (ED2) in the soft tissue adjacent to titanium implants which penetrated or did not penetrate, respectively, the peritoneal membrane of rat for 3-30 days. The penetrating implants induced a more pronounced inflammatory response at 30 days but not at earlier time points.<br/><br>
<br/><br>
PTFE and c.p. titanium, which have widely different material properties, were compared with respect to the number of macrophage subpopulations and total cells during a 12 weeks follow-up period. PTFE induced a larger accumulation of cells and a thicker capsule formation at 12 weeks insertion. However, no significant differences were seen in the macrophage subset response between the two implants.<br/><br>
<br/><br>
Variation in surface topography on polyethylene implants induced small but significant differences in the soft tissue response when examined after 1-12 weeks. The smoother surface induced the thickest capsule formation at all time points, and at 1 week it also recruited the largest number of macrophages and total cells as compared to the coarser surfaces.<br/><br>
<br/><br>
In summary, significant differences in the biological response to implanted biomaterials due to localization, material characteristics and surface topography were seen, particularly after relatively long implantation times.},
  author       = {Rosengren, Agneta},
  isbn         = {91-628-2607-7},
  keyword      = {cytochemistry,Histology,Macrophages,Cryosubstitution,Proteins,Immunohistochemistry,Titanium,Implants,PTFE,histochemistry,tissue culture,Histologi,cytokemi,histokemi,vävnadskultur},
  language     = {eng},
  pages        = {121},
  publisher    = {Inst. fysiologi och neurovetenskap, avd. neuroendokrin cellbiologi, EA-blocket, 5:e vån., Universitetssjukhuset, 221 85 Lund,},
  school       = {Lund University},
  title        = {Tissue reactions to biomaterials},
  year         = {1997},
}