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Shpichka, et al.
Table 2. Possible fibrin modifications to tune its biological properties.

Modifying agent Type of IM Type of experiments Outcomes Ref.
PLGA nanoparticles loaded Physical In vivo (diabetic mice) Promoted wound closure [46]
with VEGF and bFGF Accelerated re-epithelialization
Increased formation of granulation
tissue
Enhanced collagen synthesis
Platelet-like particles Physical In vitro Promoted cell migration [55]
In vivo (mice) Improved wound healing
TG-PDGF.AB Covalent In vivo (pigs) Enhanced wound healing [47]
KGF Covalent In vitro Increased cell migration [48]
In vivo (mice) Improved wound healing
RGD, IKVAV, YIGSR, and Cocrosslinking In vitro (dorsal root Enhanced neurite outgrowth [56]
RNIAEIIKDI ganglia dissected from
chicken embryos)
In vivo (rats) Improved axons regeneration
Bifunctional carboxylated Covalent In vitro Maintained cell proliferation [57]
N-hydroxysulfosuccinimide- Increased ALP activity
active ester PEG Up-regulated osteoblast-specific genes
In vivo (nude mice) Formation of soft vascularized
connective tissue
O,O′-bis[2-(N-succinimidyl- Covalent In vitro (MSC Promoted better sprouting [58]
succinylamino)ethyl]PEG spheroids)
TG-VEGF121 Covalent In vivo (VEGFR2-luc Enhanced vessel formation [59]
mice) SMC stabilization
Fusion proteins LN-TGF-β1 Covalent In vitro Enhanced contractile function of [60]
and LNG-TGF-β1 vascular constructs
T1 peptide sequence from Covalent In vitro Improved cellular sprouting without [61]
CCN1 adding VEGF
Increased effects when VEGF is added
In vivo (CAM) Stimulated formation of new vessels
Anti-VEGF aptamer and anti- Covalent In vivo (mice) Enhanced blood vessel growth [62]
PDGF-BB aptamer Affinity
TG-PDGF.AB Covalent In vivo (rats) Decreased flap tissue necrosis [63]
Enhanced perfusion
Maturation of new vessels
Vector containing the Physical In vivo (rats) Prolonged flap survival for 7 days after [64]
VEGF-A cDNA surgery

Increased perfusion of tissues

Higher VEGF-A expression
Abbreviations. Ref: References; ALP: Alkaline phosphatase activity; bFGF: Basic fibroblast growth factor; CAM: Chorioallantoic membrane; IM: Immobilization; KGF: Keratinocyte
growth factor; MSC: Mesenchymal stromal cells; PDGF: Platelet-derived growth factor; PEG: Polyethylene glycol; PLGA: Poly(lactic-co-glycolic acid); SMC: Smooth muscle
cells; TG: Transglutaminase; TGF-β: Transforming growth factor beta; VEGF: Vascular endothelial growth factor
improvement of wound healing in severe burns . Except pure fibrin and the mentioned above
[47]
Muhamed et al. fabricated fibrin nanoparticles, modifications, there is also platelet-rich fibrin
[48]
which were modified with keratinocyte growth (PRF) that is so-called the “second-generation
factor (KGF) by its coupling using carbodiimide platelet concentrate” . This review does not go
[49]
derivative and N-hydroxysulfosuccinimide. These into details regarding this type of fibrin-based
particles had higher healing potential that those products. The reader can learn more about it from
from non-loaded ones. the following publications [49-54] .

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