TABLE III.
Natural and synthetic biomaterials being used to facilitate angiogenesis.
| Natural biomatrices | ||||
|---|---|---|---|---|
| Biomaterial | Composition | Characteristics | Application and modifications | Example outcomes |
| Alginate | α-L-glucuronic acid and β-D-mannuronic acid | Non-toxic, temperature-independent | GF encapsulation in microspheres/beads and angiogenic induction, heparin conjugation | Slow and continuous FGF2 release and enhanced coronary circulation,164 sustained VEGF release from alginate beads and enhanced EC growth165 |
| Encapsulation of MSCs into Alginate-gelatin cross-linked hydrogel (ADA-GEL) microcapsules by means of AV loop166 | ||||
| Agarose | Agarose | Solid | GF release from beads and angiogenic induction, heparin conjugation | Local FGF2 release and augmented arteriogenesis167 |
| HUVECs sprouting withing Agarose (AG) + HA + Fibrinogen (FGN) microbeads promote vascularization168 | ||||
| Hyaluronic acid (HA) | N-acetyl-D-glucosamine and glucuronic acid | Anionic, non-sulfated, biodegradable, biocompatible | Controlled and sustained GF delivery from hydrogels and angiogenic induction, chitosan crosslinkage and adhesion peptides | Local and sustained VEGF and Ang-1 release from HA hydrogels, enhanced vessel sprouting and maturation169 |
| Chitosan | D-glucosamine and N-acetyl-D-glucosamine | Biocompatible, biodegradable, water-soluble, bioadhesive | GF encapsulation in microspheres and angiogenic induction, HA, or collagen crosslinkage | Sustained and controlled FGF1 release and promoted neoangiogenesis170 |
| Platelet-rich plasma (PRP)-Chitosan hybrid induce angiogenesis171 | ||||
| Fibrin | Fibrin monomers | Proangiogenic, weak, injectable | GF encapsulation or covalent conjugation in fibrin gel and angiogenic induction, heparin conjugation | Controlled and sustained covalently conjugated VEGF delivery, augmented local neovascularization172 |
| T1-functionalized fibrin hydrogels promotes therapeutic vascularization173 | ||||
| Collagen and gelatin | Collagen type I | Lower loading capacity, strong, biocompatible, biodegradable, permeable, porous, proangiogenic | GF encapsulation or covalent conjugation and angiogenic induction, heparin crosslinkage, chitosan crosslinkage and adhesion peptides | Prolonged and local VEGF delivery,174 augmented FGF2-mediated HUVEC growth and vascularization175 |
| BMP-2 delivery with decorin-supplemented collagen hydrogels for revascularization of bone-muscle injury176 | ||||
| Elastin | Elastin monomers and microfibrils like fibrillin | Flexible | Angiogenic induction, heparin crosslinkage | Enhanced vessel sprouting by activated ECs and pericytes177 |
| Matrigel | Various ECM molecules such as collagen type IV, entactin and laminin | Proangiogenic, biocompatible, biodegradable, solid | In vitro EC culturing and capillary tube formation, in vivo angiogenesis and 2D and 3D tissue network mimicking | Augmented 2D solid endothelial cord networks with MSCs in rat aorta culture178 |
| Microspheres | Natural polymers such as alginate, chitosan, and gelatin | Biocompatible, biodegradable, high surface-to-volume ratio, micro and nano-scale production, hydrophilic | Angiogenic induction, local and sustained delivery of encapsulated GFs, heparin crosslinkage | Local and prolonged VEGF release from calcium alginate microspheres and augmented microvessel formation125 |
| VEGF co-culture with dental pulp stem cells (DPSCs) to promote blood vessels and pulp-like tissue179 | ||||
| Synthetic biomatrices | ||||
| Biomaterial | Composition | Characteristics | Application | Outcomes |
| PLGA | Lactide and glycolide polyesters | Bioadhesive, water-insoluble, solid, porous, amorphous, biodegradable | Angiogenic induction by encapsulating or conjugating GFs, cells and ECM molecules, controlled single or multiple GF release, heparin crosslinkage and adhesion peptides | Distinct release rates of VEGF and PDGF-BB, their sustained and local release and augmented vascularization and maturation154 |
| PLGA-based bioartificial devices pre-vascularized with hypo-MSCs180 | ||||
| PEG hydrogel | PEG macromers | High viscoelasticity, biodegradable, biocompatible, water-soluble, hydrophilic, non-adhesive, photopolymerisable | ECM mimicking, angiogenic induction, avoidance of non-specific cell adhesion and intimal thickening, controlled release of encapsulated or chemically conjugated GFs, heparin crosslinkage, adhesion peptides, proteolytic cleavage sites | Augmented EC and SMC proliferation, HUVEC migration and angiogenesis by controlled and local delivery of covalently immobilized PDGF-BB181 |
| HUVECs and 10T1/2 co-culture within PEG hydrogel promotes prevascularization182 | ||||
| Peptide amphiphiles (PA) | Amino acids sequence and alkyl tail | Biocompatible, biodegradable, soft, hydrophobic, nanofiber formation, pH-sensitive | ECM or GF activity mimicking, angiogenic induction, heparin crosslinkage and adhesion peptides, hierarchical organization | Augmented neovascularization by controlled VEGF and FGF2 release from heparin-crosslinked gels183 |
| Microspheres | Synthetic polymers such as PLGA and polycaprolactones | Biocompatible, biodegradable, high surface-to-volume ratio, micro- and nano-scale production, lipophilic | Angiogenic induction, local and sustained delivery of encapsulated GFs, heparin crosslinkage | Enhanced blood vessel formation and angiogenic chemokine expression by controlled release of PDGF-BB from PLGA microspheres184 |