Electrospining: Electrospun drug-loaded polycaprolactone/polycaprolactone-gelatin multifunctional double-layer nanofiber composite scaffold for wound healing after surgery of cutaneous squamous cell carcinoma

Background

Skin cancer, including cutaneous squamous cell carcinoma (cSCC), melanoma, and basal cell carcinoma (BCC), is the most common malignant cancer in humans. In particular, cSCC, a malignancy that originates from the squamous epithelial cells of the skin, is the most common type of metastatic skin cancer, and its incidence is increasing worldwide. Over the past 30 years, new cases of cSCC have increased by 263%, and this growth trend is expected to continue due to the increase in the elderly population. The treatment modalities available for cSCC include surgical resection, radiotherapy, photodynamic therapy, immunotherapy, and targeted drug therapybb0. Despite these options, the 5-year survival rate of cSCC remains at 25-50%. Currently, surgical resection remains the preferred treatment for most patients with cSCC. However, this approach may not only cause unnecessary damage to the surrounding healthy tissues, but also leave residual tumor cells, which significantly increases the risk of local recurrence and micrometastasis. In addition, surgical resection is more likely to induce wound healing disorders and infection, leading to severe damage to skin function and aesthetics, as well as an increased likelihood of postoperative complications. Therefore, it is crucial to develop skin substitutes for postoperative wound care that can effectively prevent local recurrence and metastasis of cSCC and promote the repair of damaged tissue after resection.

The main point of this paper

Application of electrospinning technology:

Electrospinning technology is widely used to prepare nanofiber scaffolds that simulate extracellular matrix (ECM) for wound dressings to promote wound healing and skin regeneration.

Demand for double-layer wound dressings:

Double-layer wound dressings can simulate the structure and function of human skin. The outer layer acts as a barrier to prevent dehydration and bacterial invasion, and the inner layer absorbs exudate to keep the wound moist.

Material selection:

Polycaprolactone (PCL) and gelatin (Gel) are selected as the inner and outer layer materials of double-layer dressings. PCL is used as the outer layer due to its mechanical properties and biocompatibility, while Gel is used as the inner layer due to its hydrophilicity and promotion of cell proliferation.

Challenges of drug carriers:

The chemotherapy drug bleomycin (BLM) and the antibiotic enrofloxacin (ENR) are used in double-layer scaffolds to solve the problems of postoperative bacterial infection and tumor recurrence.

Advantages of drug carriers:

Nano drug carriers such as nanoparticles and nanofibers can ensure that chemotherapy drugs are delivered to the tumor site more safely and effectively, reducing systemic side effects.

Drug-loaded double-layer nanofibrous skin scaffold: an innovative strategy for wound care after cSCC surgery

cSCC surgical challenges:

cSCC tumor resection surgery has the risk of incomplete cancer cell removal and local recurrence, and large surgical wounds are prone to infection, which brings challenges to surgery.

Preparation of drug-loaded double-layer nanofiber skin scaffold:

A multifunctional double-layer nanofiber skin scaffold was prepared using electrospinning technology for cSCC postoperative wound care.

Preparation of antibacterial outer layer:

The antibacterial drug enrofloxacin (ENR) was loaded into polycaprolactone (PCL) nanofibers to form an antibacterial nanofiber membrane (PCL-ENR) as the outer layer of the scaffold.

Preparation of anticancer inner layer:

The anticancer drug bleomycin (BLM) was loaded into PCL/gelatin (Gel) nanofibers to form an anticancer nanofiber membrane (PG-BLM) as the inner layer of the scaffold.

Drug loading and physicochemical properties:

ENR and BLM were successfully loaded into the scaffold, and the scaffold showed excellent physicochemical properties. The outer layer was hydrophobic and antibacterial, and the inner layer was hydrophilic and anticancer.

Summary

In this study, electrospinning technology was used to prepare a drug-loaded multifunctional double-layer nanofiber composite skin scaffold PCL-ENR@PG-BLM for cSCC postoperative wound care. FTIR results showed that the antibacterial drug ENR and the anticancer drug BLM were successfully loaded into the skin scaffold. The outer scaffold PCL-ENR has excellent hydrophobicity and antibacterial activity, and the inner scaffold PG-BLM has good hydrophilicity. The elongation at break of PCL-ENR@PG-BLM is 26.35±1.61%, and the tensile modulus is 15.25±1.56 MPa. The results of in vitro cell experiments showed that the prepared double-layer skin scaffold had no obvious cytotoxic effect on HaCaT cells, could support the adhesion and proliferation of HaCaT, had a significant anticancer effect on A431 cells, and inhibited the proliferation of A431 cells. In addition, the biocompatibility and anticancer activity of PCL-ENR@PG-BLM were verified by in vivo animal experiments. PCL-ENR@PG-BLM repaired the wound after cSCC resection by promoting the formation of blood vessels and collagen fibers and inhibiting inflammation and proliferation of residual skin tumor cells. In summary, the prepared PCL-ENR@PG-BLM can provide a practical method for wound healing after cSCC resection.