Electrospun Hyaluronan Nanofiber Membrane Immobilizing Aromatic Doxorubicin as Therapeutic and Regenerative Biomaterial

Abstract

Lesioned tissue requires synchronous control of disease and regeneration progression after surgery. It is necessary to develop therapeutic and regenerative scaffolds. Here, hyaluronic acid (HA) was esterified with benzyl groups to prepare hyaluronic acid derivative (HA-Bn) nanofibers via electrospinning. Electrospun membranes with average fiber diameters of 407.64 ± 124.8 nm (H400), 642.3 ± 228.76 nm (H600), and 841.09 ± 236.86 nm (H800) were obtained by adjusting the spinning parameters. These fibrous membranes had good biocompatibility, among which the H400 group could promote the proliferation and spread of L929 cells. Using the postoperative treatment of malignant skin melanoma as an example, the anticancer drug doxorubicin (DOX) was encapsulated in nanofibers via hybrid electrospinning. The UV spectroscopy of DOX-loaded nanofibers (HA-DOX) revealed that DOX was successfully encapsulated, and there was a π–π interaction between aromatic DOX and HA-Bn. The drug release profile confirmed the sustained release of about 90%, achieved within 7 days. In vitro cell experiments proved that the HA-DOX nanofiber had a considerable inhibitory effect on B16F10 cells. Therefore, the HA-Bn electrospun membrane could facilitate the potential regeneration of injured skin tissues and be incorporated with drugs to achieve therapeutic effects, offering a powerful approach to developing therapeutic and regenerative biomaterial.

Chemical Modifications in Hyaluronic Acid‐Based Electrospun Scaffolds

“…In the following, some examples of electrospun grafted HA will be discussed (Table 3). wound-dressing for chronic diabetic wounds [38] benzyl bromide HA-benzyl ester/ Doxorubicin Doxorubicin encapsulation anti-melanoma drug delivery system [39] C 8 /C 12 /C 18 Alkyl Amine + EDA alkylated-HA/ PVA/HPβCD/dexamethasone EDC/NHS crosslinking scaffold for periodontal regeneration [40] Temporin Ra HA/Chitosan/PVA Peptide Loading Antimicrobial wound healing dressing [52] REDV peptide (P1) PCL Layer-by-layer deposition of PDDA [a] , SePEI [b] RGD-TCO [c] (P4) PCL-Tz [d] LbL deposition of HA-TCO and HA-Tz + final P4-TCO deposition therapeutic implants for the treatment of vocal fold scarring [80] Ac-KGGPQVTRGDVFTMP (P5) PVA/HA P5 conjugation with EDC/NHS on glutaraldehyde crosslinked nanofibers Scaffold for iPSCs growth and proliferation [81] [a]…”

“…In vitro cell experiments demonstrated that HA-DOX nanofiber had a considerable inhibitory effect on murine melanoma cell-lines. [39] The introduction of alkylamine pendant moieties at different lengths (C x ) to HA (HA-EDA-C x ) was carried out by Federico et al and the osteoinductive potential of HA-based electrospun scaffolds was evaluated). [40] HA derivatives were blended with PVA and 2-hydroxypropylcyclodextrin to improve electrospinning process.…”

Nanofiber Scaffolds as Drug Delivery Systems Promoting Wound Healing

“…Natural polymers suitable for the preparation of nanofibers mainly fall into two categories: polysaccharides and proteins. Polysaccharides include chitosan [ 60 ], starch [ 61 ], alginates [ 62 ], hyaluronic acid [ 63 ], and cellulose [ 64 ]; while protein-based polymers include collagen [ 65 ], gelatin [ 66 ], fibrinogen [ 67 ], silk proteins [ 68 ], sericin [ 69 ], elastin [ 70 ], keratin [ 71 ], and plant proteins [ 72 ]. Table 1 lists the polymers that can be used to prepare nanofibrous scaffolds.…”

“…Blended electrospinning allows for the fabrication of drug-loaded nanofiber scaffolds by combining drugs with scaffold materials and then utilizing electrospinning technology [ 63 ]. This approach allows for excellent biocompatibility and mechanical properties, making them suitable for various biomedical applications [ 199 ].…”