Production of 3D Printed Bi-Layer and Tri-Layer Sandwich Scaffolds with Polycaprolactone and Poly (vinyl alcohol)-Metformin towards Diabetic Wound Healing

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by impaired insulin secretion, sensitivity, and hyperglycemia. Diabetic wounds are one of the significant complications of T2DM owing to its difficulty in normal healing, resulting in chronic wounds. In the present work, PCL/PVA, PCL/PVA/PCL, and metformin-loaded, PCL/PVA-Met and PCL/PVA-Met/PCL hybrid scaffolds with different designs were fabricated using 3D printing. The porosity and morphological analysis of 3D-printed scaffolds were performed using scanning electron microscopy (SEM). The scaffolds’ average pore sizes were between 63.6 ± 4.0 and 112.9 ± 3.0 μm. Molecular and chemical interactions between polymers and the drug were investigated with Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Mechanical, thermal, and degradation analysis of the scaffolds were undertaken to investigate the physico-chemical characteristics of the scaffolds. Owing to the structure, PCL/PVA/PCL sandwich scaffolds had lower degradation rates than the bi-layer scaffolds. The drug release of the metformin-loaded scaffolds was evaluated with UV spectrometry, and the biocompatibility of the scaffolds on fibroblast cells was determined by cell culture analysis. The drug release in the PCL/PVA-Met scaffold was sustained till six days, whereas in the PCL/PVA-Met/PCL, it continued for 31 days. In the study of drug release kinetics, PCL/PVA-Met and PCL/PVA-Met/PCL scaffolds showed the highest correlation coefficients (R2) values for the first-order release model at 0.8735 and 0.889, respectively. Since the layered structures in the literature are mainly obtained with the electrospun fiber structures, these biocompatible sandwich scaffolds, produced for the first time with 3D-printing technology, may offer an alternative to existing drug delivery systems and may be a promising candidate for enhancing diabetic wound healing.

Effect of Diabetes on Wound Healing: A Bibliometrics and Visual Analysis

“…Researchers are experimenting with using 3D-printed artificial skin or stents to promote the healing diabetic ulcers. [56][57][58] 5. Immunomodulatory treatment: Because of decreased immune function in diabetic patients, some new treatment methods promote the healing of ulcers through immune regulation.…”

Metformin: A Potential Treatment for Acne, Hidradenitis Suppurativa and Rosacea

“…In another study, metformin inhibited the HIF-1α-dependent epithelial-to-mesenchymal transition of keloid fibroblasts ( 80 ). Efforts have also been made to generate a metformin-releasing multilayered 3-D scaffold to alleviate fibrosis and accelerate wound healing ( 81 , 82 ). Further studies are needed to investigate the anti-fibrotic effects of metformin in acne vulgaris, HS and rosacea, which have shared pathways in fibrosis and are well-known to cause scars.…”

Blend Electrospinning of Nigella sativa-Incorporating PCL/PLA/HA Fibers and Its Investigation for Bone Healing Applications

“…Polylactic acid (PLA) and polycaprolactone (PCL) are among the synthetic polymers widely used in BTE. PLA and PCL are preferred due to their biocompatibility, biodegradation, nontoxic effects, and controllable degradation rates after administration to the human body . PCL is a semicrystalline polyester widely used as a biomaterial in medical applications.…”

“…PLA and PCL are preferred due to their biocompatibility, biodegradation, nontoxic effects, and controllable degradation rates after administration to the human body. 12 PCL is a semicrystalline polyester widely used as a biomaterial in medical applications. PCL has a low melting point (55 °C) and favorable properties for bone tissue regeneration such as porosity and reabsorption.…”