Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation

Abstract Gradients of soluble factors play an important role in many biological processes, including blood vessel assembly. Gradients can be studied in detail in vitro , but methods that enable the study of spatially distributed soluble factors and multi-cellular processes in vivo are limited. Here,...

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Bibliographic Details
Published in:Biomaterials 2015-12, Vol.72, p.61-73
Main Authors: Akar, Banu, Jiang, Bin, Somo, Sami I, Appel, Alyssa A, Larson, Jeffery C, Tichauer, Kenneth M, Brey, Eric M
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Biocompatibility
Biocompatible Materials - pharmacology
Biomaterials
Biomedical materials
Blood Vessels - drug effects
Blood Vessels - growth & development
Blood Vessels - physiology
Collagen - metabolism
Dentistry
Diffusion
Gradient
Growth factors
Humans
Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology
In vivo testing
In vivo tests
Male
Near infrared fluorescence imaging
Neovascularization, Physiologic - drug effects
PDGF-BB
Porosity
Proto-Oncogene Proteins c-sis - pharmacology
Rats, Inbred Lew
Regeneration - drug effects
Solubility
Surgical implants
Three dimensional
Tissue Scaffolds - chemistry
Vascularization
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Summary:Abstract Gradients of soluble factors play an important role in many biological processes, including blood vessel assembly. Gradients can be studied in detail in vitro , but methods that enable the study of spatially distributed soluble factors and multi-cellular processes in vivo are limited. Here, we report on a method for the generation of persistent in vivo gradients of growth factors in a three-dimensional (3D) biomaterial system. Fibrin loaded porous poly (ethylene glycol) (PEG) scaffolds were generated using a particulate leaching method. Platelet derived growth factor BB (PDGF-BB) was encapsulated into poly (lactic-co-glycolic acid) (PLGA) microspheres which were placed distal to the tissue–material interface. PLGA provides sustained release of PDGF-BB and its diffusion through the porous structure results in gradient formation. Gradients within the scaffold were confirmed in vivo using near-infrared fluorescence imaging and gradients were present for more than 3 weeks. The diffusion of PDGF-BB was modeled and verified with in vivo imaging findings. The depth of tissue invasion and density of blood vessels formed in response to the biomaterial increased with magnitude of the gradient. This biomaterial system allows for generation of sustained growth factor gradients for the study of tissue response to gradients in vivo.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2015.08.049