Nanofibrous asymmetric collagen/curcumin membrane containing aspirin-loaded PLGA nanoparticles for guided bone regeneration

Mohammad Ali Ghavimi,Solmaz Maleki Dizaj,Simin Sharifi,Mohammad Yousef Memar,Amirhossein Bani Shahabadi,Seyedhosein Jarolmasjed

doi:10.1038/s41598-020-75454-2

Mohammad Ali Ghavimi, Solmaz Maleki Dizaj + Show 4 more

Open Access

https://doi.org/10.1038/s41598-020-75454-2

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Abstract

The goal of the current study was to develop an asymmetric guided bone regeneration (GBR) membrane benefiting from curcumin and aspirin. The membrane was prepared using electrospinning technique and then was physic-chemically characterized by the conventional methods. The release profile of aspirin from the prepared membrane was also measured by ultraviolet spectrophotometry. Also, the antibacterial activities of the membrane was evaluated. We also assessed the in vitro effects of the prepared membrane on the biocompatibility and osteogenic differentiation of dental pulp stem cells (DPSCs), and evaluated in vivo bone regeneration using the prepared membrane in the defects created in both sides of the dog’s jaw by histology. The results from the characterization specified that the membrane was successfully prepared with monodispersed nanosized fibers, uniform network shaped morphology, negative surface charge and sustained release platform for aspirin. The membrane also showed antimicrobial effects against all tested bacteria. The presence of curcumin and aspirin in the asymmetric membrane enhanced osteogenic potential at both transcriptional and translational levels. The results of the animal test showed that the test area was completely filled with new bone after just 28 days, while the commercial membrane area remained empty. There was also a soft tissue layer above the new bone area in the test side. We suggested that the prepared membrane in this work could be used as a GBR membrane to keep soft tissue from occupying bone defects in GBR surgeries. Besides, the surgeries can be benefited from antibacterial activities and bone healing effects of this novel GBR membrane while, simultaneously, promoting bone regeneration.

Highlights

Bone defects are considered among the common devastating problems worldwide
Fetal bovine serum (FBS), Dulbecco’s modified Eagle’s medium (DMEM), Dulbecco’s phosphate buffer saline (DPBS), trypsin, penicillin G and streptomycin were achieved from Gibco (Life Technologies, Carlsbad, CA, USA). poly lactic-co-glycolic acid (PLGA (75:25), Acetylsalicylic acid (Aspirin), curcumin, collagen (Bovine type), Dimethylsulfoxide (DMSO), MTT (3-[4,5-dimethyl-thiazol-2-yl]2,5-diphenyl-tetrazoliumbromide), paraformaldehyde, glycerol phosphate, ascorbic acid, dexamethasone, RIPA buffer, protease inhibitor cocktail, Alkaline Phosphatase Assay Kit, QuantiPro BCA Assay Kit were bought from Sigma-Aldrich (Darmstadt, Germany)
Processing variables for the electrospinning process including needle to collector distance, voltage, flow rate, solution parameters such as surface tension, viscosity, and electrical conductivity of the solution can control the morphology of the n anofibers[8]

Summary

Introduction

Bone defects are considered among the common devastating problems worldwide. bone grafting has been applied in the clinic to solve this issue, it has been reported that the rapid migration of fibroblasts to the defect or fracture site can shape a fibrous capsule which prohibits the efficient growth of blood vessels and osteoblasts into the graft tissue and result in bone nonunion[1]. Satisfactory degradation and mechanical specifications in order to produce proper barrier functionalities, space maintenance and clinical handling should be the essential properties of used m embranes[4,5] Enhancing these properties and the ability to complete new bone regeneration via membrane materials is an important research field in bone regeneration. Electro-spinning as a conventional textile industry using polymer science has lately been introduced as a novel strategy in the production of nanoscale biomimetic scaffolds in tissue engineering. It is a promising controlled drug delivery system which allows the incorporation of therapeutic agents into the non-woven nanofiber meshes during the electrospinning p rocess[2]. Owing to its outstanding biocompatibility and biodegradability, collagen membranes have been applied in the GBR technique and have shown suitable clinical o utcomes[9]

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