Hydrogels are promising candidates that mimic the native skin microenvironment due to their porous and hydrated molecular structure.
Study: Gelatin/alginate-based nanocomposite enriched with wet electrospun nanofibers as a biomimetic single-dose skin substitute. Image Credit: Impact Photography/Shutterstock.com
In a paper recently published in the journal ACS Applied Bio Materials, nanofiber (NF) reinforced hydrogel (HG) nanocomposites were fabricated for wound healing. The NF-enriched HG mimicked the extracellular matrix (ECM) and served as a skin substitute for wound healing.
The NF-reinforced HG matrix was composed of sodium alginate (SA) and gelatin (GE), antimicrobial Punica granatum extract (PE) with hyaluronic acid (HA). Additionally, HG nanocomposites crosslinked with N-(3-(dimethylamino)propyl)-N’-ethyl carbodiimide hydrochloride (EDC) were reinforced with cellulose acetate/polycaprolactone (PCL/CA) fragmented NFs charged of trans-ferulic acid (FA). .
The nanofibers used to fortify the HG nanocomposites were prepared by wet electrospinning the poly(vinyl alcohol) (PVA) coagulant solution, to mimic porous ECM fibers. The reinforced skin substitute designed for wound healing application provided the ability to tune mechanical and physical properties, as well as their inherent porous microstructure.
HG nanocomposites engineered for wound healing were characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and electron microscopy. Additionally, HG nanocomposites were investigated for their biocompatibility, biodegradability, bioactivity, and drug release kinetics in vitro to confirm their practical applicability in wound healing.
Nanocomposites in the wound healing process
Wound healing is a complex skin repair process that begins immediately after an injury to the epidermal layer and can take days or even years. This dynamic healing process includes highly organized cellular, humoral and molecular mechanisms. Wound healing has three overlapping phases: inflammation, proliferation, and remodeling. Any disruption of these phases could lead to abnormal wound healing.
A nanocomposite is a combination of two or more materials, of which the nanomaterial is at least one of the components, with unique physicochemical properties. Nanocomposite materials are engineered to exhibit properties that exceed the capabilities of the sum of their constituents. The materials embedded in the nanocomposites are called the reinforcing materials embedded in another material called the matrix.
The current trend in regenerative medicine encourages the replacement of damaged natural tissue with three-dimensional (3D) skin substitutes, representing the natural ECM. Therefore, the skin substitute improves the interactions of cellular materials and promotes tissue regeneration. To this end, hydrogels serve as water-rich 3D scaffolds, exhibiting elastic properties like natural soft tissues.
Although the porosity of hydrogels allows the absorption of exudates and maintains water balance, they lack mechanical properties and are very susceptible to degradation. However, inserting nanofibers into the cross-linked hydrogel matrix yields hybrid-enriched nanocomposites, which exhibit an optimal pore structure that maintains water balance and prevents cell migration in 3D hydrogels.
NF-enriched gelatin/alginate nanocomposites for wound healing
In the present work, an HG-based skin substitute was developed from ECM mimicking NF-enhanced HG nanocomposites and evaluated for its healing ability. The HG matrix which served as skin substitute was composed of antimicrobial agent SA, GE, PE and vital components HA, as in natural ECM.
Crosslinking of HG with the crosslinking agent EDC and reinforcement with FA-loaded fragmented PCL/CA NFs yielded highly competent nanocomposites, in which the nanofibers were fabricated by wet electrospinning in a PVA coagulant solution, resembling ECM fibers. Additionally, this 3D hybrid array was hypothesized to help cells identify both NF structure and the water-rich environment, mimicking the ECM.
In addition, the designed skin substitute had tunable mechanical properties, excellent physical properties and a highly porous microstructure. Characterization results revealed that single and FA-charged NFs had mean diameters of 210 ± 12 and 452 ± 25 nanometers, respectively.
Additionally, a full-thickness excision defect model was considered to perform live studies to evaluate the healing and skin regeneration properties of the engineered HG nanocomposites. The results showed that the constructed HG nanocomposites exhibited good antimicrobial properties, cytocompatibility, free radical scavenging activity, water absorption capacity, porosity and good bioavailability.
Moreover, the ECM-mimicking HG nanocomposites showed outstanding healing activity with their single-dose treatment ability against wounds of 0.95 millimeters in diameter after 15 days. Moreover, with the help of histological study of the wound area, it was observed that HG nanocomposites which served as skin substitutes could enhance the wound healing process and enhance skin regeneration.
In summary, a skin substitute mimicking natural ECM was made by reinforcing the HG matrix with NFs. The developed HG nanocomposites were incorporated with key components of the native ECM. Therefore, the skin substitute was composed of GE/SA HG fortified with fragmented PCL/CA NF.
The manufacturing method was easy without the need for complicated and difficult techniques. The prepared HG nanocomposites showed tunable mechanical characteristics, excellent physical properties and a highly porous microstructure. Additionally, the HG nanocomposite has the advantage of being a single-dose skin substitute for effective wound healing and skin regeneration.
Aboomeirah, AA., Sarhan, WA., Khalil, EA., Abdellatif, A., Dena, ASA., El-Sherbiny, IM. (2022) Wet electrospun nanofiber fortified gelatin/alginate nanocomposite as a single-dose biomimetic skin substitute. Applied Biological Materials ACS.https://pubs.acs.org/doi/10.1021/acsabm.2c00147