Table 3.
Functionalization with bioactive molecules and their applications in tissue engineering.
| Bioactive Molecule | Method of Functionalization | Research/Study | Outcome of Biofunctionalization | Cells Used/Tissue to Regenerate |
|---|---|---|---|---|
| Collagen [94] | Remote plasma treatment followed by immobilization of collagen on the nanofibersurface | PCL nanofibers were electrospun and layered with collagen | Collagen coating improved hydrophilicity and increased cell proliferation compared to non-coated PCL nanofibers | Primary human dermal fibroblasts (HDFs)/ Dermal tissue |
| Collagen [95] | Coaxial electrospinning technique and by soaking the PCL matrix in collagen solution | PCL nanofibers were electrospun and coated with collagen using two techniques | Density of human dermal fibroblasts on collagen layered PCL nanofibers prepared using coaxial electrospinning increased linearly compared to roughly collagen coated and uncoated PCL nanofibers | Human dermal fibroblasts/Dermal tissue |
| Gelatin [96] | Air plasma treatment followed by covalent grafting of gelatin molecules | PCL nanofibers were electrospun and grafted with gelatin molecules | Viability and proliferation rate of fibroblast cells increased in biofunctionalized nanofibers compared to tissue culture polystyrene (TCPS) | Fibroblast cells/Tissue engineering |
| Fibronectin [97] | Three different approaches were used -protein surface entrapment, chemical functionalization and coaxial electrospinning | PCL nanofibers were electrospun and functionalized with fibronectin using three approaches | Improved cell adhesion and proliferation of bone murine stromal cells was observed for scaffolds functionalized using all the three approaches, but sample with the surface entrapment of fibronectin demonstrated better performance. | Bone murine stromal cells/ bone tissue |
| Fibronectin [98] | Immersing in fibronectin solution overnight. | PCL nanofibers were electrospun with radial alignment and coated with fibronectin | Improved cell adhesion, cell migration and helped in more uniform distribution of cells. Boosted the effect of topographic cues offered by the fiber alignment. | Dural fibroblast cells/dural tissue |
| RGD [99] | RGD peptide was conjugated on nanofibers using Polyethylene glycol as a spacer. | Polyurethane electrospun matrix was immobilized with RGD peptide. | Improved viability, promoted proliferation of cells in comparison with an unaltered surface. | Human umbilical vein endothelial cells/vascular tissue |
| RGD [100] | RGD functionalization via strain-promoted azide–alkyne cycloaddition. | PCL aligned nanofibers were electrospun and functionalized with RGD peptide. | RGD functionalization decreased muscular atrophy and hastened sensory recovery. Facilitated regeneration of sciatic nerve in animal model compared to non-functionalized nanofibers. | Rat sciatic nerve repair |
| RGD [101] | Chemical conjugation of RGD on nanofibers was carried out, after activation of carboxyl groups of polymer | Polybutylene adipate-co-terephthalate (PBAT)/gelatin elctrospun nanofibers were loaded with Doxycycline and modified using RGD | RGD functionalized PBAT/gelatin nanofibers showed notably improved wound closure and histopathological results with re-epithelialization and angiogenesis in animal model compared to the control groups. | Dermal wounds |
| Aspartic acid (ASP) and Glutamic acid (GLU) Templated Peptides [102] | Cold atmospheric plasma (CAP) was used to modify the nanofiber surface and to mediate the conjugation with peptides | PLGA nanofiberswere electrospun and conjugated with peptides | Peptide conjugation improved the osteoinductive capacity of nanofibers. ASP templated peptide conjugation to nanofibers increased the expression of key osteogenic markers and induced cell proliferation more than GLU templated peptide conjugated nanofibers. |
Human bone marrow derived mesenchymal stem cells/bone tissue |
| Laminin [103] | Physical coating method and the chemical bonding method used for functionalization of the surfaceof the nanofiber | Slow-degrading silica nanofibers were electrospun and attached with Laminin on the surface | Nanofibers with covalently attached laminin showed significantly longer neurite extensions than those observed on unmodified nanofibers and nanofibers subjected to physical adsorption of laminin. | Rat pheochromocytoma cell line/neuron |
| Laminin [104] | covalent binding, physical adsorption or blended electrospinning procedures. | PLLA nanofibers were electrospun and modified with laminin. | Functionalized nanofibers were capable of enhancing axonal extensions. In comparison to covalent immobilized and physical adsorbed, blending for electrospinning of laminin and synthetic polymer is a simple and effective method to functionalize nanofibers |
Rat pheochromocytoma cell-line PC12 cells/neurons |
| Laminin [105] | Functionalization with laminin usingcarbodiimide based crosslinking and physical adsorption method | Nanofibers were electrospun from the blends of poly(caprolactone) (PCL) and chitosan and modified with laminin | Number of cells attached and the rate of proliferation on the laminincoated scaffolds were higher than those of pure PCL and PCL-chitosan scaffolds. Schwann Cell attachment and proliferation were significantly higher on PCL-chitosan scaffolds with crosslinked laminin than the PCL-chitosan nanofibrous matrices with adsorbed laminin. |
Schwann Cell/nerve tissue |
| Avidin-biotin system [106] | Avidin immobilization on nanofibers | Poly(caprolactone-co-lactide)/Pluronic (PLCL/Pluronic) nanofibers were electrospun and modified with avidin. Adipose-derived stem cells (ADSCs) were modified with biotin. |
Biotinylated ADSCs showed more rapid attachment onto avidin-treated nanofibrous matrices compared to normal ADSCs adherence on untreated matrices, and the difference of attached cell number between the two groups was notable. It also promoted cell spreading on nanofibrous matrices. |
Adipose-derived stem cells (ADSCs) |
| Fibroblast Growth Factor-2 (FGF-2) [107] | FGF-2 was immobilized on the surface of the nanofibers through avidin-biotin covalent binding. | Gelatin nanofibers were electrospun, crosslinked using glutaraldehyde, and modified with FGF-2 | FGF-2 immobilization led to proportionate increase in cell proliferation and adhesion. | Adipose derived stem cells |
| Insulin [108] | Insulin was bound to carboxylic moieties of the polymer backbone through a standard carbodiimide chemistry | PCL and cellulose acetate micro-nanofibers were electrospun and functionalized with insulin. | Enhanced expression of tendon phenotypic markers by Mesenchymal stem cells (MSCs) akin to observations from insulin supplemented media, indicatedconservation of insulin bioactivity upon functionalization. | MSCs/tendon |
| Insulin-like Growth Factor-1 (IGF-1) [109] | Physical adsorption of IGF-1 due to soaking into suspension of IGF-1 in PBS and shaking for 4 h | Graphene oxide (GO)-incorporated PLGAnanofibres were electrospun and functionalized with IGF-1 | Survival, proliferation, and differentiation of neural stem cells (NSCs) was significantly increased. Higher survival rate of NSCs in the IGF-1 modifed nanofibers compared to unmodifed nanofibers was observed. |
NSCs/nerve cells |
| Polydopamine assisted bromelain [110] | Soaking in solution of dopamine and bromelain, with continuoue stirring for 8 h. Dopamine-assisted co-deposition strategy was used. |
PCL nanofibers were electrospun and immobilized with bromelain using polydopamine (PDA) to create bromelain-polydopamine-PCL (BrPDA-PCL) nanofibers | BrPDA-PCL fibers exhibited superior biocompatibility compared to PCL fibers PDA coating made scaffold hydrophilic, allowing for better cell attachment and spreading PDA and bromelain both showed anti-bacterial activity. |
L929 fibroblast cells/wound healing |
| Poly norepinephrine (pNE) [111] | Soaking in norepinephrine solution for 15 h | PCLfibers were electrospun andcoated using mussel-inspired pNE. | pNE coating improved the ECM proteins accumulation on the fibers, which supported cell adhesion and proliferation of cells on PCL fibrous membranes. | Skeletal muscle cell line L6/skeletal muscles |
| pNE mediated collagen [112] | Soaking in norepinephrine solution 16 h, followed by soaking in collagen solution overnight. | Poly(lactic acid-co-caprolactone) (PLCL) nanofibers were electrospun and coated with poly norepinephrine, followed by collagen. | pNE coating assisted in collagen anchoring to improve cell adhesion and to immobilize nerve growth factor to advance differentiation to neurons. pNE–collagen coating was observed to be the better substrate for PC12 cells differentiation. |
PC12 cells/neurons |
| Polyphenol [113] | Blend electrospinning | Polylactic acid/date palm polyphenol nanofibers were electrospun using blend electrospinning. | Both cell proliferation and cell viability were enhanced with increased polyphenol concentration within the scaffolds. Higher polyphenol content resulted into better cell migration |
NIH/3T3 fibroblast cell/wound healing |
| Vascular endothelial growth factor (VEGF) [114] | Blend and co-axial electrospinning | PCL-gelatin nanofibers were electrospun and modified with VEGF. | Functionalization improved proliferation of mesenchymal stem cells, but no significant difference in proliferartion between nanofibers manufactured with both techniques was observed. Expression of cardiac specific proteins enhanced. | Human mesenchymal stem cells/myocardium |
| VEGF [115] | Covalent coupling to VEGF by forming stable amide bond | PCL nanofibers were electrospun and modified with VEGF. | Biological activity of immobilised VEGF was maintained and functionalised substrates demonstrated to induce a higher cell number compared to non-functionalised scaffolds. | Human umbilical vein endothelial cells |
| Epidermal growth factor (EGF) and fibroblast growth factor (FGF) [28] | Blend electrospinning | PVAnanofibers were electrospun and modified with EGF and FGF. | GFs incorporated PVA nanofibers induced cell proliferation andenhanced cell survival compared to PVA control sample In in-vivo study, PVA/EGF/FGF nanofibers demonstratedquick recovery of the wounds in contrast to that of only EGF or FGF nanofibers. |
Human dermal fibroblasts/wound healing. |