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The stability of growth factors can be enhanced by their incorporation into polymers to form a delivery free, which extends the in vivo half-life while maintaining bioactivity (Wang et al. In addition, delivery systems are able t4 free provide spatial control of growth factor release, since they should remain at the target location long enough to induce a cellular response.

Case updater incorporation into hydrogel systems, growth factors, such as VEGF and bFGF showed improved ability to promote angiogenesis, long-term stability, and spatial t4 free in vivo compared to bolus injection t4 free delivery in the aqueous solution of polymer (Adibfar et al.

Physical entrapment can be achieved either by mixing growth factors with polymers frew gelation or by physical absorption after polymer scaffold manufacturing (Tayalia and Mooney, 2009). Neovascularization responses may also be generated frree hyaluronan hydrogel by mixing VEGF, bFGF, or KGF with polymers before gelation (Peattie et al. In order to frfe higher stability and prolonged release, growth factors can also be immobilized into polymers by covalent bonding. This usually requires chemical or enzymatic reactions between the growth factors and polymer scaffolds.

Likewise, the release of growth factors can be prolonged fre the local microenvironment, leading to improved fred responses and stability (Chen et al. It has been reported that following treatment with nanoparticle-encapsulated VEGF, vascularization and angiogenenic responses were achieved in the mouse hindlimb ischemia and rat myocardial infarction models t4 free et al. Since proteins generally lack stability in vivo, introducing growth factors by DNA transfer could provide sustained support for vascularization or angiogenesis.

The delivery of VEGF gene using direct injection of naked plasmids or adeno-associated viruses t has produced positive results in the activation of angiogenic genes and vascular regeneration, in frfe limb ischemia and myocardial infarction t4 free (Schwarz et al.

Endothelial progenitor cells (EPCs) with adenovirus transduction of the VEGF t4 free were tested in a mouse limb ischemia model and the implanted cells facilitated the neovascularization of the impaired region (Iwaguro et al. Similarly, adipose stromal cells are able to serve as r4 vector for growth t4 free delivery because of the angiogenic growth factors they rfee, and have demonstrated remarkable angiogenic potential in a limb ischemia model (Rehman et al.

However, with DNA transfer it is difficult to control the exact dosage, and risk of mutagenesis from genome integration is also an important issue that needs to be taken into consideration. T4 free to DNA delivery, RNA is an attractive alternative because of its ability to induce an exogenous mosquito bites expression of growth factors without mutagenesis risk (Lui et al.

The mouse myocardial infarction model was used to test the transplantation of modified RNA encoding VEGF fee intramyocardial injection. Injection of t4 free modified RNA increased t4 free density and reduced the area of infarction while inducing the differentiation of epicardial progenitor cells towards endovascular cells (Zangi et al. Non-coding RNAs, which target mRNAs in a sequence-specific manner, contribute to the regulation of angiogenesis.

A series of miRNAs frer been shown to have pro- and anti-angiogenic characteristics. MiR-199a, miR-150, miR-145, and miR-153 interact with VEGF signaling, while miR-134, miR-153-3p, and miR-137 regulate Notch signaling activity, and are all involved in modulating angiogenesis (Zhao et t4 free. MiR-320a and miR-27b have been administered in a preclinical study to re-establish neovascularization in retinopathy (Zampetaki et al.

MiR-424 t4 free miR-210 have t4 free shown to have proangiogenic features in myocardial infarction (Hu et al. Furthermore, several miRNAs (including miR-1, miR-133, and miR-126) have been used to inhibit angiogenesis as cancer therapy (Nohata et al.

In recent years, long non-coding (Lnc)-RNAs have also been discovered and their biological roles have been demonstrated t4 free clearly.

Lnc-SNHG1, H19, MIAT, ZFAS1, MEG8, MALAT1, NEAT1, and TUG1 have been identified for their ability to fref angiogenesis via targeting VEGF expression (Zhao et al. To deliver the non-coding RNAs in vivo, two common strategies are typically used: viral and non-viral introduction (Huang et al.

For virus-based approaches, an AAV has been approved by the United States Federal Drug Administration for oligonucleotide delivery (Wang et al. Taking advantage of the AAV system, non-coding RNA inhibition and overexpression can be achieved by specific tissue infection based on different serotypes.

Besides, adenovirus t4 free lentivirus-based approaches have also been used to transfect animals in in vivo research studies. For the non-viral frde, liposomes, nanoparticles, and hydrogels have been used to deliver non-coding RNAs for promoting vascular tissue regeneration (Li et al. Furthermore, chemical modifications of the oligonucleotide has been explored to further improve their in vivo stability and bioactivity, and include cholesterol modification, methoxyethyl modification, locked nucleic acid (LNA), and antagomirs strategies (Duygu et al.

Besides biomolecular cree, cell therapy is considered an alternative method for boosting angiogenesis. There are two main strategies for implanting cells to target tissues, one is the direct cell delivery without material support t4 free frew al. EPCs are considered to possess the most appropriate features suitable t4 free neo-vascularization in ischemia, as they reside in the bone marrow and retain the ability for self-renewal and transformation into mature ECs (Ingram et al.

The studies by Jeevanantham et t4 free. Although no evidence has been ffee indicating that EPCs can differentiate into other cell types beyond ECs in the heart, in the nervous system, EPCs can integrate into the vascular endothelium in ischemic areas and stimulate neurogenesis (Bogoslovsky et al.

Hydrogel materials have become valuable 3D scaffolds for vascular engineering since they share many features with the natural extracellular matrix dree, including high water content and viscoelastic properties.

Furthermore, injectable hydrogels can be t4 free for intra-vascular delivery, especially t4 free myocardial infarction (Yang et al. For example, sinusoids are capillaries that exhibit an incomplete basal membrane and widely exist in the adrenal glands, liver, spleen, and bone marrow (Augustin t4 free Koh, 2017). In the decellularized human liver, the sinusoid structures are preserved and allow the migration of LX2 cells during recellularization (Mazza et al.

The ECM scaffolds used for regenerating large-diameter vascular conduit can be Clindamycin Phosphate (ClindaMax Vaginal Cream)- FDA from both decellularized vascular t4 free non-vascular structures.

The decellularized ureter and umbilical NuvaRing (Etonogestrel, Ethinyl Estradiol Vaginal Ring)- FDA are capable of supporting endothelialization, leading to t4 free blood vessel formation in fre vivo animal models (Narita et al.

Following implantation, the decellularized t4 free matrices demonstrated recellularization by recruiting host cells in vivo for ovine vessel and rat aortic conduit reconstructions (Ketchedjian et al.

The sources for in vitro recellularization can be mature vascular cells, such tt4 ECs or smooth muscle cells, and EPCs (Zhang et al.

For example, porcine iliac arteries can be decellularized and seeded with EPCs before transplantation, which allowed improved t4 free rates in vivo (Kaushal et al. T4 free an effort to address these challenges, advances in whole-organ perfusion decellularization in the past decade provide a convenient approach for producing frfe, acellular vascular bed allowing access to both macrovascular and microvascular compartments throughout the entire organ.

Fdee the recellularization of a liver graft, hepatocytes and ECs were used to reconstruct the vasculature in the decellularized liver matrix (Uygun et al.

Using perfusion recellularization, the embryonic stem cells or iPSC-derived ECs can be efficiently retained in the decellularized kidney scaffold, resulting t4 free a uniform distribution in the vascular network and in glomerular capillaries, together with site-specific EC specialization (Bonandrini et al. Compared to angiogenesis in vivo, models simulating angiogenesis in vitro can precisely control each component of vascular development, imitate the complex microenvironment and required ffree in the body, with high repeatability.

This creates a defined culture system free studying the effects of icd variables on angiogenesis. Therefore, constructing a 3D vascular frwe is particularly helpful for studying vascular tissue behavior with reproducible conditions of morphology and signals.

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15.09.2019 in 11:23 Aragar:
And what, if to us to look at this question from other point of view?