Table 6.
Scaffold Types | Preparation Methods | Results | Ref. |
---|---|---|---|
Collagen-Based Scaffolds | |||
3D-COL biological scaffolds |
Decellularization by SDS extraction; crosslinking (EDC/NSH); enzymatic treatment to remove elastic fibers. | Mechanical properties of 3D-COL controlled by crosslinking degree; 3T3 cells adhere and proliferate on COL scaffolds and infiltrated to depth of about 20 mm after 7 days, and 40 mm after 28 days. |
[227] |
COL/NRASMC matrix | Collagen-cell suspension was cast into silicon rubber wells and cultured in an incubator. | Uniform tension, during COL compaction, increases the cell content, stimulates their metabolism and leads to stronger constructs; NRASMCs are metabolically active proved by the elastin inside and around the COL fibers, and the proteoglycans at their interface. |
[228] |
3D COL disc scaffolds | Molding technique by rapid prototyping with 3D inkjet printer | VICs proliferate more on 1% w/v COL than 2% or 5%; VICs remodel the scaffold and synthesize new matrix (detection of remodeling enzymes, MMPs and ECM gene expression). |
[229] |
COL-EL; COL-C4S heterogenous scaffolds |
Molding technique using PTFE molds, followed by freeze drying | Good cell proliferation on COL, due to natural cells binding via integrin receptors; C4S increase the cell metabolic activities; Low cell proliferation on EL, due to its non-integrinsignaling pathway. |
[230] |
COL-EL bilayer scaffolds |
Solution casting into PTFE molds; freeze drying, repeated twice to obtain bilayer structure. | Bilayer scaffolds have anisotropic bending moduli similar to native valves CDCs prefer COL over EL when proliferating, resulting in asymmetrical cell distribution in the two different layers. | [210] |
3D COL-EL hydrogels scaffolds |
COL-EL composition: 50% COL, 12% EL, 10% PBS, 28% equal parts of DMEM and FBS; pH 7.5; 37°C; 1 h. | 3D COL-EL scaffolds support cell attachment, proliferation and differentiation: after 7 days, VICs double their number and exhibited stable levels of integrin β1 and F-actin expression; VECs have a very good proliferation, but the integrin β1 expression remained low. | [231] |
3D COL-CH composites scaffolds | COL:CH (7:1, w/w) The composites were seeded with 3 types of cells: SMCs, FIs and ECs. |
3D COL-CH have good cells adhesion and support ECs differentiation; SMCs group—large number of SMCs with dense disordered arrangement; SMC+EC group: large number of scattered ECs with long shuttle shape. |
[232] |
COL-HA hybrid scaffolds | Crosslinking by EDC/NHS route. | Structure similar to fibrosa layer of the valve leaflets; CDCs attachment not affected by the pore size and stiffness. |
[233] |
Fibrin-Based Scaffolds | |||
Autologous fibrin-based heart valve scaffolds | Molding technique; In vitro: bioreactor conditioning; In vivo: implantation in sheep pulmonary trunk (3 months). |
In vitro: well-organized structure of “conditioned samples”, aligned OCAs in leaflets; cellular detachment, possible cells death in “control samples”; In vivo: fibrin scaffolds completely resorbed and replaced by ECM proteins; significant tissue development and cell distribution. |
[145,234] |
(SC-F) composites biological valves |
Coating DPPV with stem cells-fibrin complex |
Static condition: 1st day—homogenous distribution of SC; 16th day—cell colony formation in SC-F compared to control (no cell clusters); Dynamic conditions: starting with the 4th day, floating composite clots at the inner surface of the valve and leaflets are observed. |
[235] |
Fibrin-based tubular heart valves | The tube mounted on a frame with three struts which, upon back-pressure, cause the tube to collapse into three coating “leaflets”. | In vitro: excellent performance under hydrodynamic conditions, minimal RF (approx. 5%), excellent values for TGV and EOA; In vivo (sheep, 2 months): substantial recellularization and no significant change in diameter or mechanical properties. |
[236] |
Tubular construct sutured at the root circumferential line and at three single points of sinotubular junction. | Advantage of one-piece construct manufacturing method without glue; In vivo (sheep, 3 months): no thrombus formation, calcification or stenosis; formation of ECs confluent monolayer on the valve surface. |
[140] | |
Fibrin-based tube-in-stent heart valves | Fibrin gel and HUVCs molded as tube-in-stent form and sewn into a self-expandable nitinol stent. | Homogeneous cells distribution throughout the valve; The simulation of the catheter-based delivery (the valves crimping for 20 min) does not influence the valve mechanical properties or functionality. |
[120] |
F-ELR biomimetic heart valves |
Multi-step injection molding: the valve wall obtained from F gel and the leaflets from F-ELR gel. | Good structure cohesion and functionality (opening/closing cycles); Different cell type localization: the vessel-derived α-SMA negative (leaflets) and α-SMA positive cells (valve wall). | [32] |
F/PLDL-PLGA anisotropic composites BioTexValve |
Molding of PLDL multifilaments and electrospun PLGA fibers incorporated within fibrin gel. |
Anisotropic Young’s moduli comparable with the native aortic leaflets; The valve withstands aortic flow/pressure conditions in flow-loop system; Homogeneous distribution of α-SMA, aligned with the longitudinal direction of the wall and leaflets. |
[134] |
SF/LDI-PEUU nanofibrous scaffolds | SF and LDI-PEUU prepared by electrospinning process. | Smooth and porous 3D structure of SF/LDI-PEUU scaffolds with randomly oriented fibers; Good blood compatibility (hemolysis rate <5%); HUVECs have spindle-shaped morphology and good spread. |
[237] |
Abbreviations: C4S—chondroitin-4-sulfate; CDCs—cardiosphere-derived cells; CH—chitosan; DMEM—Dulbecco’s modified Eagle medium; DPPV—decellularized porcine pulmonary valve; ECs—endothelial cells; EDC—1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-hydrochloride; EL—elastin; ELR—elastin-like recombinamer; EOA—effective orifice areas; F—fibrin; FBS—fetal bovine serum; FIs—fibroblasts; HA—hyaluronic acid; HUVECs—human umbilical vein endothelial cells; HUVCs—human umbilical vein cells; LDI-PEUU—L-lysine diisocyanate poly(ester-urethane)urea; MMPs—matrix metalloproteinases; NRASMCs—neonatal rat aortic smooth muscle cells; NSH—N-hydroxysuccinimide; OCAs—ovine carotid artery-derived cells; PBS—phosphate buffered saline; PLDL—poly(L/D,L-lactide); PLGA—poly(lactic-co-glycolic acid); PTFE—polytetrafluoroethylene; RF—regurgitant fractions; SCs—stem cells; SDS—sodium dodecyl sulfate; SF—silk fibrinoin; α-SMA—α-smooth muscle actin; SMCs—smooth muscle cells; 3T3—mouse fibroblasts cells; TVG—transvalvular pressure gradients; VECs—valvular endothelial cells; VICs—valvular interstitial cells.