Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation.
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.
Department of Biomedical Engineering, Illinois Institute of Technology, United States; Research Service, Hines Veterans Administration Hospital, Hines, IL, United States.
Banu
B
Akar
Department of Biomedical Engineering, Illinois Institute of Technology, United States; Research Service, Hines Veterans Administration Hospital, Hines, IL, United States.
Bin
B
Jiang
Department of Biomedical Engineering, Illinois Institute of Technology, United States; Research Service, Hines Veterans Administration Hospital, Hines, IL, United States.
Sami I
SI
Somo
Department of Biomedical Engineering, Illinois Institute of Technology, United States; Research Service, Hines Veterans Administration Hospital, Hines, IL, United States.
Alyssa A
AA
Appel
Department of Biomedical Engineering, Illinois Institute of Technology, United States; Research Service, Hines Veterans Administration Hospital, Hines, IL, United States.
Jeffery C
JC
Larson
Department of Biomedical Engineering, Illinois Institute of Technology, United States.
Kenneth M
KM
Tichauer
Department of Biomedical Engineering, Illinois Institute of Technology, United States; Research Service, Hines Veterans Administration Hospital, Hines, IL, United States. Electronic address: brey@iit.edu.
Eric M
EM
Brey
D000818:Animals; D000077214:Becaplermin; D001672:Biocompatible Materials / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D004058:Diffusion; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016062:Porosity; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D011917:Rats, Inbred Lew; D012038:Regeneration / Q000187:drug effects; D012995:Solubility; D054457:Tissue Scaffolds / Q000737:chemistry
D001672:Biocompatible Materials; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003094:Collagen
Biomaterials; Gradient; Near infrared fluorescence imaging; PDGF-BB; Vascularization