Dynamic in vivo biocompatibility of angiogenic peptide amphiphile nanofibers.
Biomaterials that promote angiogenesis have great potential in regenerative medicine for rapid revascularization of damaged tissue, survival of transplanted cells, and healing of chronic wounds. Supramolecular nanofibers formed by self-assembly of a heparin-binding peptide amphiphile and heparan sulfate-like glycosaminoglycans were evaluated here using a dorsal skinfold chamber model to dynamically monitor the interaction between the nanofiber gel and the microcirculation, representing a novel application of this model. We paired this model with a conventional subcutaneous implantation model for static histological assessment of the interactions between the gel and host tissue. In the static analysis, the heparan sulfate-containing nanofiber gels were found to persist in the tissue for up to 30 days and revealed excellent biocompatibility. Strikingly, as the nanofiber gel biodegraded, we observed the formation of a de novo vascularized connective tissue. In the dynamic experiments using the dorsal skinfold chamber, the material again demonstrated good biocompatibility, with minimal dilation of the microcirculation and only a few adherent leukocytes, monitored through intravital fluorescence microscopy. The new application of the dorsal skinfold model corroborated our findings from the traditional static histology, demonstrating the potential use of this technique to dynamically evaluate the biocompatibility of materials. The observed biocompatibility and development of new vascularized tissue using both techniques demonstrates the potential of these angiogenesis-promoting materials for a host of regenerative strategies.
Ghanaati
Shahram
S
Institute of Pathology, Langenbeckstr. 1, Johannes Gutenberg University, 55101 Mainz, Germany. ghanaati@uni-mainz.de
Webber
Matthew J
MJ
Unger
Ronald E
RE
Orth
Carina
C
Hulvat
James F
JF
Kiehna
Sarah E
SE
Barbeck
Mike
M
Rasic
Angela
A
Stupp
Samuel I
SI
Kirkpatrick
C James
CJ
D042501:Angiogenic Proteins / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D005260:Female; D006497:Heparan Sulfate / Q000737:chemistry; D020007:Implants, Experimental; D051379:Mice; D008833:Microcirculation; D008856:Microscopy, Fluorescence
D042501:Angiogenic Proteins; D001672:Biocompatible Materials; D006497:Heparan Sulfate
J Biomed Mater Res A. 2006 Jul;78(1):157-67
16619254
FASEB J. 2002 Aug;16(10):1316-8
12060671
Nano Lett. 2006 Sep;6(9):2086-90
16968030
J Phys Chem B. 2008 Feb 28;112(8):2326-34
18251531
Biomaterials. 2008 Jan;29(2):161-71
17936353
Nano Lett. 2005 Jan;5(1):1-4
15792402
Biomaterials. 2007 Nov;28(31):4608-18
17662383
J Biol Chem. 1997 Jun 27;272(26):16382-9
9195945
J Neurosci. 2008 Apr 2;28(14):3814-23
18385339
Res Exp Med (Berl). 1980;177(2):125-34
7003665
BMJ. 2002 Jan 19;324(7330):160-3
11799036
J Tissue Eng Regen Med. 2008 Dec;2(8):455-62
18850672
Science. 1997 Apr 4;276(5309):75-81
9082989
J Clin Invest. 2003 Apr;111(7):952-4
12671043
Transplantation. 2008 Aug 15;86(3):478-81
18698254
J Vasc Surg. 2008 Jan;47(1):173-82
18178471
Biomaterials. 2008 Dec;29(34):4501-9
18774605
Nano Lett. 2005 Feb;5(2):249-52
15794605
Eur Surg Res. 2002 Jan-Apr;34(1-2):83-91
11867907
Science. 2004 Feb 27;303(5662):1352-5
14739465
Biomaterials. 2009 Mar;30(7):1329-38
19091396
Biomacromolecules. 2006 Jun;7(6):1855-63
16768407
J Exp Med. 1973 Oct 1;138(4):745-53
4744009
Biomaterials. 2008 Aug;29(23):3298-305
18468676
Int J Microcirc Clin Exp. 1995 Mar-Apr;15(2):85-91
8655257
Science. 1993 May 14;260(5110):920-6
8493529
Science. 2001 Nov 23;294(5547):1684-8
11721046
Arch Pathol. 1964 Jul;78:69-72
14150734
Nat Med. 2003 Jun;9(6):669-76
12778165
Lancet Oncol. 2002 Jan;3(1):35-43
11905603
Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5133-8
11929981
Bioconjug Chem. 2005 Nov-Dec;16(6):1343-8
16287227
Nature. 2000 Sep 14;407(6801):249-57
11001068
Semin Cancer Biol. 1992 Apr;3(2):81-7
1378313
AMA Arch Pathol. 1955 Sep;60(3):289-95
13248341
Acta Biomater. 2005 Jul;1(4):387-97
16701820
Biomaterials. 2008 Mar;29(8):1085-98
18083225
Mol Cell. 2000 Sep;6(3):743-50
11030354