**4. Electrospinning with the GEL/COL system**

by the FTIR spectra, while the thermal studies revealed that the melting and crystallinity temperatures of the scaffolds were slightly shifted to a lower value. Both HEC/PVAL and HEC/PVAL/COL fibers showed a significant decrease in Young's modulus and tensile stress during the 12 weeks of degradation. Their results demonstrate that these nanofibrous scaffolds showed degradation behavior that meets the requirements as a degradable biomaterial

The development of biomaterials with the capacity to induce the healing of cutaneous wounds is a great challenge in biomedicine. In one study, COL sponges were developed from tilapia skin and electro-nylon nanofibers for wound dressing. It was found that nanofibers could significantly promote the proliferation of human keratinocytes and stimulate epidermal differentiation through the expression of regulated genes involved, filaggrin and type I transglutaminase in human keratinocytes. In addition, COL nanofibers could also facilitate the regeneration of rat skin, in one study, electrolyzed nanofibers of COL were prepared from biomimetic tilapia skin and were shown to have a good bioactivity and could accelerate the healing of wounds from rat quickly and efficiently. These biological effects can be attributed to the structure of the biomimetic extracellular matrix and to the multiple amino acids of the COL nanofibers. Therefore, tilapia COL nanofibers could be used as a new wound dressing, effectively avoiding the risk of transmitting diseases in

Another study using the double-extrusion electrospinning technique prepared with multilayer 3D scaffolds stacking poly-lactic-co-glycolic acid (PLGA) microfiber membranes alternately to micro- /nano-mixed fibrous membranes of PLGA and COL. The density of the COL fibers in multilayered scaffolds obtained was able to control the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. Demonstrating that the homogeneous dispersion of glutamic acid-modified hydroxyapatite nanoparticles (nHA-GA) in the COL solution improved the osteogenic properties of the multilayer scaffolds fabricated. In addition, it found that PLGA-COL-HA micro-nano fibrous scaffolds were highly bioactive compared to pristine microfibrous PLGA and PLGA and COL micro/nano-mixed fibrous

The development of biomimetic scaffolds represents a promising direction in the engineering of bone tissue. This was demonstrated by Ma *et al.* [27], when they designed a two-step process to prepare a type of biomimetic hybrid hydrogels that were composed of COL, hydroxyapatite, and alendronate, the latter as anti-osteoporosis drug. These hybrid hydrogels of collagen, hydroxyapatite, and alendronate exhibited remarkably improved mechanical properties (G: 38–187 kPa storage modulus), higher gel contents, and lower swelling proportions compared to hydrogels prepared from COL only under similar conditions. In addition, they showed degradable behaviors against collagenase. The hybrid hydrogels of COL-hydroxyapatitealendronate well supported the adhesion and growth of MC3T3-E1 osteoblastic cells. Such resistant but enzymatically degradable hybrid hydrogels hold the potential as scaffolds for

The hybrid constructs from marine organism material for porous scaffolds of COL, such as fibrillated jellyfish and alginate hydrogel, mimic the two major components of cartilage,

potential for dermal replacement.

20 Tissue Regeneration

future clinical application [25].

platforms [26].

bone tissue engineering.

Angarano *et al.* [29] synthesized GEL and COL cross-linked fibers by the reactive electrospinning technique using a mixture of nontoxic solvents: acetic acid, ethyl acetate, and water (5, 3, and 2 w/w/w), eliminating fluorinated solvents, which require post-treatment and purification by the implementation of glyoxal, represented an easy, versatile, and one-step procedure. Enabling the expansion and fabrication of synthetic fabrics of COL based on nanofiber cross-linked GEL in situ. This in situ cross-linking renders the water soluble GEL fibers water resistant without adversely affecting the hydrophilicity, excellent wetting of fibers, cell compatibility, reabsorption, cell adhesion, and proliferation typical of COL nonwoven nanofibers cross-linked.

Tylingo *et al*. [30] prepared and characterized new porous scaffolds composed of chitosan, COL, and GEL for the preparation of GEL and COL scaffolds isolated from fish skin with various physicochemical properties. All biomaterials obtained showed homogeneous porosity. The type of protein polymer determined the rheology and mechanical properties of the preparation of the preparations. The use of protein polymers decreased the swelling ability of the materials by about 30% compared to the materials obtained from chitosan. GEL-containing materials showed the highest solubility (approximately 30%). Scaffolds obtained in 100% chitosan were found to be harder than COL materials by an average of 30% and less flexible more than twice. In addition, materials containing protein polymers showed good antioxidant properties.


In **Table 1**, other studies with the electrospinning technique are summarized.


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**Table 1.** Gelatin and collagen uses in biomedical applications.
