The Incorporation of Etanercept into a Porous Tri-Layer Scaffold for Restoring and Repairing Cartilage Tissue.

Yaima Campos,Gastón Fuentes,Carla Jorquera-Cordero,Luis J Cruz,Timo Schomann,Chih Kit Chung,Luis Quintanilla,Amisel Almirall,Alan Chan,Ivo Que,José C Rodríguez-Cabello

doi:10.3390/pharmaceutics14020282

Abstract

Cartilage diseases currently affect a high percentage of the world’s population. Almost all of these diseases, such as osteoarthritis (OA), cause inflammation of this soft tissue. However, this could be controlled with biomaterials that act as an anti-inflammatory delivery system, capable of dosing these drugs over time in a specific area. The objective of this study was to incorporate etanercept (ETA) into porous three-layer scaffolds to decrease the inflammatory process in this soft tissue. ETA is a blocker of pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). For this reason, the scaffold was built based on natural polymers, including chitosan and type I collagen. The scaffold was grafted next to subchondral bone using hydroxyapatite as filler. One of the biomaterials obtained was also crosslinked to compare its mechanical properties with the non-treated one. Both samples’ physicochemical properties were studied with SEM, micro-CT and photoacoustic imaging, and their rheological properties were also compared. The cell viability and proliferation of the human chondrocyte C28/I2 cell line were studied in vitro. An in vitro and in vivo controlled release study was evaluated in both specimens. The ETA anti-inflammatory effect was also studied by in vitro TNF-α and IL-6 production. The crosslinked and non-treated scaffolds had rheological properties suitable for this application. They were non-cytotoxic and favoured the in vitro growth of chondrocytes. The in vitro and in vivo ETA release showed desirable results for a drug delivery system. The TNF-α and IL-6 production assay showed that this drug was effective as an anti-inflammatory agent. In an in vivo OA mice model, safranin-O and fast green staining was carried out. The OA cartilage tissue improved when the scaffold with ETA was grafted in the damaged area. These results demonstrate that this type of biomaterial has high potential for clinical applications in tissue engineering and as a controlled drug delivery system in OA articular cartilage.

Highlights

Introduction distributed under the terms andCartilage is a soft tissue located in several areas of the body coating joints
The morphology of the scaffold must be porous in order to allow the interchange of fluids, nutrients and cells once it is grafted in the damaged area of the knee
The scaffold was crosslinked and its morphology was compared with the non-crosslinked material

Summary

Introduction

Introduction distributed under the terms andCartilage is a soft tissue located in several areas of the body coating joints. Its main function is to protect joints from cyclic stresses, preventing wear by friction and allowing movement Some factors, such as mechanical, genetic and biochemical factors, can disrupt chondrocyte–matrix associations and alter metabolic responses in the chondrocytes [1]. Pharmaceutics 2022, 14, 282 can lead to OA, which is a slowly progressive disease that is very common in the elderly and sportive populations. It is frequently found in the hip, knee, distal phalangeal and intervertebral joints. It is difficult for cartilage to recover because it lacks lymphatic and blood vessels and it has a scant cellular population Since their joint function is remarkably affected, the daily living and social activities of patients with OA are restricted

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