Control of in vivo microvessel ingrowth by modulation of biomaterial local architecture and chemistry.
We developed a method for controlling local architecture and chemistry simultaneously in biomaterial implants to control microvessel ingrowth in vivo. Porous polypropylene disks (5 mm in diameter and 40 microm thick) were plasma-coated with a fluoropolymer and then laser-drilled with 50-microm-diameter holes through their thickness. We then oxidized the disks to create hydroxyl functionality on the exposed polypropylene (inside the holes). Acrylamide was grafted to the hydroxyl groups through polymerization in the presence of activating ceric ions. Staining with toluidine blue O demonstrated that grafting occurred only inside the holes. We used the Hoffman degradation reaction to convert the amide groups of acrylamide to amine groups, and then we used ethylene glycol diglycidyl ether to attach biomolecules of interest inside the holes: secreted protein acidic and rich in cysteine (SPARC) peptide Lys-Gly-His-Lys (KGHK; angiogenic), thrombospondin-2 (TSP; antiangiogenic), or albumin (rat; neutral). In vivo testing in a rat subcutaneous dorsum model for a 3-week interval demonstrated a greater vessel surface area (p = 0.032) and a greater number of vessels (p = 0.043) in tissue local to the holes with KGHK-immobilized disks than with TSP-immobilized disks. However, differences between KGHK-immobilized and albumin-immobilized disks were less significant (p = 0.120 and p = 0.289 for the vessel surface area and number of vessels, respectively). The developed methods have potential applications in biomaterial design applications for which selective neovascularization is desired.
Sanders
J E
JE
Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA. jsanders@u.washington.edu
Baker
A B
AB
Golledge
S L
SL
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002196:Capillaries / Q000166:cytology / Q000254:growth & development*; D004396:Coloring Agents; D004731:Endotoxins / Q000494:pharmacology; D007834:Lasers; D008567:Membranes, Artificial; D008855:Microscopy, Electron, Scanning; D010949:Plasma; D011126:Polypropylenes; D016062:Porosity; D011506:Proteins / Q000737:chemistry; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties
D001672:Biocompatible Materials; D004396:Coloring Agents; D004731:Endotoxins; D008567:Membranes, Artificial; D011126:Polypropylenes; D011506:Proteins