Tailoring nanofibrous matrices-a material with much promise for wound healing applications-to simultaneously mitigate bacterial colonization and stimulate wound closure of infected wounds is highly desirable. To that end, a dual-releasing, multiscale system of biodegradable electrospun nanofibers coated with biocompatible micellar nanocarriers is reported. For wound healing, transforming growth factor-β1 is incorporated into polycaprolactone/collagen (PCL/Coll) nanofibers via electrospinning and the myofibroblastic differentiation of human dermal fibroblasts is locally stimulated. To prevent infection, biocompatible nanocarriers of polypeptide-based block copolymer micelles are deposited onto the surfaces of PCL/Coll nanofibers using tannic acid as a binding partner. Micelle-modified fibrous scaffolds are favorable for wound healing, not only supporting the attachment and spreading of fibroblasts comparable to those on noncoated nanofibers, but also significantly enhancing fibroblast migration. Micellar coatings can be loaded with gentamicin or clindamycin and exhibit antibacterial activity as measured by Petrifilm and zone of inhibition assays as well as time-dependent reduction of cellular counts of Staphylococcus aureus cultures. Moreover, delivery time of antibiotic dosage is tunable through the application of a novel modular approach. Altogether, this system holds great promise as an infection-mitigating, cell-stimulating, biodegradable skin graft for wound management and tissue engineering.
In recognition of the potential of calreticulin (CRT)
protein in
enhancing the rate and quality of wound healing in excisional animal
wound models, this study was to incorporate CRT via polyblend electrospinning
into polycaprolactone (PCL)/type 1 collagen (Col1) nanofibers (NFs;
334 ± 75 nm diameter) as biomimetic extracellular matrices to
provide a novel mode of delivery and protection of CRT with enhanced
synergistic activities for tissue regeneration. Release kinetic studies
using fluoresceinated CRT (CRT-FITC) polyblend NFs showed a burst
release within 4 h reaching a plateau at 72 h, with further intervals
of release upon incubation with fresh phosphate buffered saline for
up to 8 weeks. By measuring fluorescence during the first 4 h of release,
CRT-FITC-containing NFs were shown to protect CRT from proteolytic
digestion (e.g., by subtilisin) compared to CRT-FITC in solution.
CRT incorporated into NFs (CRT-NFs) also showed retention of biological
activities and potency for stimulating proliferation and migration
of human keratinocytes and fibroblasts. Fibroblasts seeded on CRT-NFs,
after 2 days, showed increased amounts of fibronectin, TGF-β1,
and integrin β1 in cell lysates by immunoblotting. Compared
to NFs without CRT, CRT-NFs supported cell responses consistent with
greater cell polarization and increased laminin-5 deposition of keratinocytes
and a more motile phenotype of fibroblasts, as suggested by vinculin-capping
F-actin fibers nonuniformly located throughout the cell body and the
secretion of phosphorylated focal adhesion kinase-enriched migrasomes.
Altogether, CRT electrospun into PCL/Col1 NFs retained its structural
integrity and biological functions while having additional benefits
of customizable loading, protection of CRT from proteolytic degradation,
and sustained release of CRT from NFs, coupled with innate physicochemical
cues of biomimetic PCL/Col1 NFs. Such synergistic activities have
potential for healing recalcitrant wounds such as diabetic foot ulcers.
Healing of chronic wounds is challenging because of the imbalance of growth factors and common occurrence of infection. In article https://doi.org/10.1002/adhm.201800132, Svetlana A. Sukhishvili and co‐workers develop a dual‐releasing, multiscale system of biodegradable nanofibers to simultaneously accelerate wound healing and mitigate bacterial infection. A unique strategy of submicron topography provided by the surface‐bound polymer micelles enables accelerated wound healing and supported localized delivery of antibiotics. Cover image designed and produced by Victor Selin.
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