In Vivo Biocompatibility of Electrospun Biodegradable Dual Carrier (Antibiotic + Growth Factor) in a Mouse Model-Implications for Rapid Wound Healing.

Charu Dwivedi,Ajay Vikram Singh,Avinash C Pandey,Pramod W Ramteke,Himanshu Pandey,Andreas Luch,Peter Laux,Sandip Patil

doi:10.3390/pharmaceutics11040180

Abstract

Tissue engineering technologies involving growth factors have produced one of the most advanced generations of diabetic wound healing solutions. Using this approach, a nanocomposite carrier was designed using Poly(d,l-lactide-co-glycolide) (PLGA)/Gelatin polymer solutions for the simultaneous release of recombinant human epidermal growth factor (rhEGF) and gentamicin sulfate at the wound site to hasten the process of diabetic wound healing and inactivation of bacterial growth. The physicochemical characterization of the fabricated scaffolds was carried out using scanning electron microscopy (SEM) and X-ay diffraction (XRD). The scaffolds were analyzed for thermal stability using thermogravimetric analysis and differential scanning calorimetry. The porosity, biodegradability, and swelling behavior of the scaffolds was also evaluated. Encapsulation efficiency, drug loading capacity, and in vitro drug release were also investigated. Further, the bacterial inhibition percentage and detailed in vivo biocompatibility for wound healing efficiency was performed on diabetic C57BL6 mice with dorsal wounds. The scaffolds exhibited excellent wound healing and continuous proliferation of cells for 12 days. These results support the applicability of such systems in rapid healing of diabetic wounds and ulcers.

Highlights

Wound healing or tissue repair is a complex multistep process comprising a multitude of cells, cytokines, extracellular matrix (ECM) molecules, blood cells, and a number of other factors [1]
The results indicate that gentamicin sulfate loaded scaffolds possess efficient antibacterial property and can be effectively used in the treatment of wound healing or dermal bacterial infections, thereby, proving a potential application for use as a drug delivery and as a wound dressing agent [50]
We studied the morphologies and biovolume of bacterial cells seeded on two nanofibrous scaffold supplemented with Gentamicin Sulfate (GS) using laser scanning microscope to quantify surface and biovolume (Figure 5F–G and Supplementary Figure S2A–E)

Summary

Introduction

Wound healing or tissue repair is a complex multistep process comprising a multitude of cells, cytokines, extracellular matrix (ECM) molecules, blood cells, and a number of other factors [1]. Disturbances at proliferation or inflammation phases of wound healing lead to perturbations in the process [2]. Chronic wounds, such as those in diabetic patients, present worldwide health challenges as well as an economic burden. Since diabetes lowers the normal immunity of the body, such patients are more prone to infection in wounds [5] Chronic wounds, such as leg ulcers, foot ulcers, and pressure ulcers, are more prone to such microbial infections due to the presence of multiple microbial populations consisting of S. aureus [6], P. aeruginosa [7], coliform bacteria [8], Streptococcus spp., and Enterococcus spp. The patient may develop a more serious deep-wound infection, and require amputation due to the occurrence of anaerobic bacteria in diabetic foot ulcers and may lead to abscess or granuloma formation [10,11]

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