skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Extracellular matrix and growth factor engineering for controlled angiogenesis in regenerative medicine.

Journal Article · · Frontiers in Bioengineering and Biotechnology

Blood vessel growth plays a key role in regenerative medicine, both to restore blood supply to ischemic tissues and to ensure rapid vascularization of clinical-size tissue-engineered grafts. For example, vascular endothelial growth factor (VEGF) is the master regulator of physiological blood vessel growth and is one of the main molecular targets of therapeutic angiogenesis approaches. However, angiogenesis is a complex process and there is a need to develop rational therapeutic strategies based on a firm understanding of basic vascular biology principles, as evidenced by the disappointing results of initial clinical trials of angiogenic factor delivery. In particular, the spatial localization of angiogenic signals in the extracellular matrix (ECM) is crucial to ensure the proper assembly and maturation of new vascular structures. Here, we discuss the therapeutic implications of matrix interactions of angiogenic factors, with a special emphasis on VEGF, as well as provide an overview of current approaches, based on protein and biomaterial engineering that mimic the regulatory functions of ECM to optimize the signaling microenvironment of vascular growth factors.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
European Research Council (ERC); University Hospital of Basel; Swiss National Science Foundation (SNSF); USDOE Office of Science - Office of Basic Energy Sciences - Materials Sciences and Engineering Division
DOE Contract Number:
AC02-06CH11357
OSTI ID:
1238795
Journal Information:
Frontiers in Bioengineering and Biotechnology, Vol. 4; ISSN 2296-4185
Publisher:
Frontiers Research Foundation
Country of Publication:
United States
Language:
English

References (89)

Tenascin C Promiscuously Binds Growth Factors via Its Fifth Fibronectin Type III-Like Domain journal April 2013
Induction of Aberrant Vascular Growth, But Not of Normal Angiogenesis, by Cell-Based Expression of Different Doses of Human and Mouse VEGF Is Species-Dependent journal February 2013
High-Throughput Flow Cytometry Purification of Transduced Progenitors Expressing Defined Levels of Vascular Endothelial Growth Factor Induces Controlled Angiogenesis In Vivo journal December 2009
Update on therapeutic vascularization strategies journal January 2009
VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia journal June 2003
Evaluation of angiogenesis and side effects in ischemic rabbit hindlimbs after intramuscular injection of adenoviral vectors encoding VEGF and LacZ: Gene Therapy for Angiogenesis journal May 2002
Gene Therapy for Ischemic Cardiovascular Diseases: Some Lessons Learned from the First Clinical Trials journal November 2004
Polymers for pro- and anti-angiogenic therapy journal April 2007
Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis journal October 2002
Growth factor delivery-based tissue engineering: general approaches and a review of recent developments journal June 2010
The shunt problem: control of functional shunting in normal and tumour vasculature journal July 2010
The role of actively released fibrin-conjugated VEGF for VEGF receptor 2 gene activation and the enhancement of angiogenesis journal April 2008
Therapeutic angiogenesis for critical limb ischaemia journal May 2013
Strategic Directions in Tissue Engineering journal December 2007
The well-tempered vessel journal May 2001
FACS-purified myoblasts producing controlled VEGF levels induce safe and stable angiogenesis in chronic hind limb ischemia journal December 2011
VEGF gene therapy: stimulating angiogenesis or angioma-genesis? journal October 2000
Increased angiogenesis and blood vessel maturation in acellular collagen–heparin scaffolds containing both FGF2 and VEGF journal February 2007
The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. journal December 1993
Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction journal July 2007
Critical role of microenvironmental factors in angiogenesis journal May 2005
Adipose tissue-derived progenitors for engineering osteogenic and vasculogenic grafts journal July 2010
The Extracellular Matrix: Not Just Pretty Fibrils journal November 2009
Vascularization in Tissue Engineering book October 2020
Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) journal January 2007
Growth factor binding to the pericellular matrix and its importance in tissue engineering☆ journal November 2007
The 12th–14th type III repeats of fibronectin function as a highly promiscuous growth factor-binding domain journal December 2010
Cell-Demanded Liberation of VEGF 121 From Fibrin Implants Induces Local and Controlled Blood Vessel Growth journal April 2004
The 12th–14th type III repeats of fibronectin function as a highly promiscuous growth factor‐binding domain journal July 2010
New aspects in vascular gene therapy journal April 2010
Basic and Therapeutic Aspects of Angiogenesis journal September 2011
Vascularization in tissue engineering journal August 2008
Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering text January 2007
Long-lasting fibrin matrices ensure stable and functional angiogenesis by highly tunable, sustained delivery of recombinant VEGF164 journal April 2014
Integrin regulation of growth factor receptors journal April 2002
The promotion of myocardial repair by the sequential delivery of IGF-1 and HGF from an injectable alginate biomaterial in a model of acute myocardial infarction journal January 2011
Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor journal February 2011
VEGF Gene Delivery to Muscle journal November 1998
Long-lasting fibrin matrices ensure stable and functional angiogenesis by highly tunable, sustained delivery of recombinant VEGF164 text January 2014
Inducible adeno-associated virus vectors promote functional angiogenesis in adult organisms via regulated vascular endothelial growth factor expression journal May 2009
Long-lasting fibrin matrices ensure stable and functional angiogenesis by highly tunable, sustained delivery of recombinant VEGF164 text January 2014
Controlled Angiogenesis in the Heart by Cell-Based Expression of Specific Vascular Endothelial Growth Factor Levels journal October 2012
Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia journal December 2006
Heparin-regulated release of growth factors in vitro and angiogenic response in vivo to implanted hyaluronan hydrogels containing VEGF and bFGF journal October 2006
Enhancing microvascular formation and vessel maturation through temporal control over multiple pro-angiogenic and pro-maturation factors journal December 2013
Conditional switching of VEGF provides new insights into adult neovascularization and pro-angiogenic therapy journal April 2002
Heart Disease and Stroke Statistics—2013 Update: A Report From the American Heart Association journal January 2013
Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix journal March 2013
Polymeric system for dual growth factor delivery journal November 2001
Therapeutic angiogenesis due to balanced single-vector delivery of VEGF and PDGF-BB journal June 2012
Specific VEGF sequestering and release using peptide-functionalized hydrogel microspheres journal April 2012
Extracellular Matrix and Cytokines: A Functional Unit journal January 2000
Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering journal September 2007
Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis journal February 2004
Functional muscle regeneration with combined delivery of angiogenesis and myogenesis factors journal December 2009
Engineering the Growth Factor Microenvironment with Fibronectin Domains to Promote Wound and Bone Tissue Healing journal September 2011
Agent-based simulation of notch-mediated tip cell selection in angiogenic sprout initialisation journal January 2008
Positional Control of Cell Fate Through Joint Integrin/Receptor Protein Kinase Signaling journal November 2003
Vasculogenic bio-synthetic hydrogel for enhancement of pancreatic islet engraftment and function in type 1 diabetes journal June 2013
Heterogeneity of the Angiogenic Response Induced in Different Normal Adult Tissues by Vascular Permeability Factor/Vascular Endothelial Growth Factor journal January 2000
Cell-demanded release of VEGF from synthetic, biointeractive cell ingrowth matrices for vascularized tissue growth journal December 2003
Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall journal August 2003
Conditional switching of VEGF provides new insights into adult neovascularization and pro-angiogenic therapy. text January 2002
VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond journal March 2012
Identification of a cell retention signal in the B-chain of platelet-derived growth factor and in the long splice version of the A-chain. journal July 1991
Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele journal April 1996
Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis journal January 2007
Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene journal April 1996
Growth Factors Engineered for Super-Affinity to the Extracellular Matrix Enhance Tissue Healing journal February 2014
Therapeutic angiogenesis: controlled delivery of angiogenic factors journal June 2012
Vitronectin: Growth Factor Complexes Hold Potential as a Wound Therapy Approach journal June 2008
Long-term VEGF-A expression promotes aberrant angiogenesis and fibrosis in skeletal muscle journal May 2011
The role of actively released fibrin-conjugated VEGF for VEGF receptor 2 gene activation and the enhancement of angiogenesis text January 2008
The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165 journal August 2013
Embryonic development is disrupted by modest increases in vascular endothelial growth factor gene expression journal September 2000
Glomeruloid Microvascular Proliferation Follows Adenoviral Vascular Permeability Factor/Vascular Endothelial Growth Factor-164 Gene Delivery journal March 2001
Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb journal August 1996
Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat—angiogenesis and angioma formation journal April 2000
Interactions between growth factor receptors and adhesion molecules: breaking the rules journal October 2003
Local Delivery of VEGF and SDF Enhances Endothelial Progenitor Cell Recruitment and Resultant Recovery from Ischemia journal April 2015
Release of basic fibroblast growth factor from a crosslinked glycosaminoglycan hydrogel promotes wound healing journal March 2007
Interactions between extracellular matrix and growth factors in wound healing journal March 2009
VEGF Gene Delivery to Myocardium: Deleterious Effects of Unregulated Expression journal August 2000
Angiogenic Gene Therapy for Experimental Critical Limb Ischemia: Acceleration of Limb Loss by Overexpression of Vascular Endothelial Growth Factor 165 but not of Fibroblast Growth Factor-2 journal May 2002
Heparin-II Domain of Fibronectin Is a Vascular Endothelial Growth Factor-Binding Domain: Enhancement of VEGF Biological Activity by a Singular Growth Factor/Matrix Protein Synergism journal October 2006
Human Studies of Angiogenic Gene Therapy journal October 2009
Blood Flow Remodels Growing Vasculature During Vascular Endothelial Growth Factor Gene Therapy and Determines Between Capillary Arterialization and Sprouting Angiogenesis journal December 2005
The “Heart Disease and Stroke Statistics—2013 Update” and the Need for a National Cardiovascular Surveillance System journal January 2013
Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis journal February 2004

Cited By (28)

3D Cardiac Cell Culture: A Critical Review of Current Technologies and Applications journal June 2019
Therapeutic vascularization in regenerative medicine journal April 2020
TGF-β1/CD105 signaling controls vascular network formation within growth factor sequestering hyaluronic acid hydrogels journal March 2018
It Takes Two to Tang: Coupling of Angiogenesis and Osteogenesis for Bone Regeneration text January 2017
3D Cardiac Cell Culture: A Critical Review of Current Technologies and Applications text January 2019
EphrinB2/EphB4 signaling regulates non-sprouting angiogenesis by VEGF text January 2018
4D Biomaterials for Light‐Guided Angiogenesis collection January 2018
Rational Design of Prevascularized Large 3D Tissue Constructs Using Computational Simulations and Biofabrication of Geometrically Controlled Microvessels journal May 2016
A sulfonated reversible thermal gel for the spatiotemporal control of VEGF delivery to promote therapeutic angiogenesis: Sulfonated reversible thermal gel for control of VEGF delivery journal September 2018
In vitro selection technologies to enhance biomaterial functionality journal May 2016
Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment? journal December 2016
Biofabrication strategies for creating microvascular complexity journal April 2019
Tethering QK peptide to enhance angiogenesis in elastin-like recombinamer (ELR) hydrogels journal February 2019
State-of-the-Art Strategies for the Vascularization of Three-Dimensional Engineered Organs journal June 2019
Design principles for therapeutic angiogenic materials journal January 2016
Cultured cell‐derived extracellular matrices to enhance the osteogenic differentiation and angiogenic properties of human mesenchymal stem/stromal cells
  • Carvalho, Marta S.; Silva, João C.; Cabral, Joaquim M. S.
  • Journal of Tissue Engineering and Regenerative Medicine, Vol. 13, Issue 9 https://doi.org/10.1002/term.2907
journal July 2019
EphrinB2/EphB4 signaling regulates non‐sprouting angiogenesis by VEGF journal April 2018
Prevascularized bladder acellular matrix hydrogel/silk fibroin composite scaffolds promote the regeneration of urethra in a rabbit model journal October 2018
It Takes Two to Tango: Coupling of Angiogenesis and Osteogenesis for Bone Regeneration journal November 2017
Angiogenesis-promoted bone repair with silicate-shelled hydrogel fiber scaffolds journal January 2019
Growth factors with enhanced syndecan binding generate tonic signalling and promote tissue healing journal November 2019
Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study Cancer-Microenvironment Interactions? journal January 2018
Mechanical Interaction Between Cells Facilitates Molecular Transport text January 2019
Mechanical Interaction between Cells Facilitates Molecular Transport journal November 2019
Gellan Gum Hydrogels with Enzyme-Sensitive Biodegradation and Endothelial Cell Biorecognition Sites journal February 2018
4D Biomaterials for Light‐Guided Angiogenesis journal December 2018
Learning from Mother Nature: Innovative Tools to Boost Endogenous Repair of Critical or Difficult-to-Heal Large Tissue Defects journal April 2017
Preparation and characteristics of gelatin sponges crosslinked by microbial transglutaminase journal August 2017

Similar Records

Extracellular matrix and growth factor engineering for controlled angiogenesis in regenerative medicine
Journal Article · Wed Apr 01 00:00:00 EDT 2015 · Frontiers in Bioengineering and Biotechnology · OSTI ID:1238795

Extracellular Matrix-Inspired Growth Factor Delivery Systems for Skin Wound Healing
Journal Article · Sat Aug 01 00:00:00 EDT 2015 · Advances in Wound Care · OSTI ID:1238795

Decreased cell adhesion promotes angiogenesis in a Pyk2-dependent manner
Journal Article · Mon Aug 01 00:00:00 EDT 2011 · Experimental Cell Research · OSTI ID:1238795

Related Subjects