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Contactless magnetically responsive injectable hydrogel for aligned tissue regeneration.

ABSTRACT: Cellular alignment plays a pivotal role in several human tissues, including skeletal muscle, spinal cord and tendon. Various techniques have been developed to control cellular alignment using 3D biomaterials. However, the majority of 3D-aligned scaffolds require invasive surgery for implantation. In contrast, injectable hydrogels provide a non-invasive delivery method, gaining considerable attention for the treatment of diverse conditions, including osteochondral lesions, volumetric muscle loss, and traumatic brain injury. We engineered a biomimetic hydrogel with magnetic responsiveness by combining gellan gum, hyaluronic acid, collagen, and magnetic nanoparticles (MNPs). Collagen type I was paired with MNPs to form magnetic collagen bundles (MCollB), allowing the orientation control of these bundles within the hydrogel matrix through the application of a remote low-intensity magnetic field. This resulted in the creation of an anisotropic architecture. The hydrogel mechanical properties were comparable to those of human soft tissues, such as skeletal muscle, and proof of the aligned hydrogel concept was demonstrated. In vitro findings confirmed the absence of toxicity and pro-inflammatory effects. Notably, an increased fibroblast cell proliferation and pro-regenerative activation of macrophages were observed. The in-vivo study further validated the hydrogel biocompatibility and demonstrated the feasibility of injection with rapid in situ gelation. Consequently, this magnetically controlled injectable hydrogel exhibits significant promise as a minimally invasive, rapid gelling and effective treatment for regenerating various aligned human tissues.

SUBMITTER: Rossi A

PROVIDER: S-EPMC11360152 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Contactless magnetically responsive injectable hydrogel for aligned tissue regeneration.

Rossi Arianna A Furlani Franco F Bassi Giada G Cunha Carla C Lunghi Alice A Molinari Filippo F Teran Francisco J FJ Lista Florigio F Bianchi Michele M Piperno Anna A Montesi Monica M Panseri Silvia S

Materials today. Bio 20240603

Cellular alignment plays a pivotal role in several human tissues, including skeletal muscle, spinal cord and tendon. Various techniques have been developed to control cellular alignment using 3D biomaterials. However, the majority of 3D-aligned scaffolds require invasive surgery for implantation. In contrast, injectable hydrogels provide a non-invasive delivery method, gaining considerable attention for the treatment of diverse conditions, including osteochondral lesions, volumetric muscle loss, ...[more]

PMID: 39211510

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Project description:Currently, bone infections caused by diseases or injuries are a major health issue. In addition, the conventional therapeutic approaches used to treat bone diseases or injuries present several drawbacks. In the area of tissue engineering, researchers have been developing new alternative therapeutic approaches, such as scaffolds, to promote the regeneration of injured tissues. Despite the advantages of these materials, most of them require an invasive surgical procedure. To overcome these problems, the main focus of this work was to develop scaffolds for bone regeneration, which can be applied using injectable hydrogels that circumvent the use of invasive procedures, while allowing for bone regeneration. Throughout this work, injectable hydrogels were developed based on a natural polymer, dextran, along with the use of two inorganic compounds, calcium β-triphosphate and nanohydroxyapatite, that aimed to reinforce the mechanical properties of the 3D mesh. The materials were chemically characterized considering the requirements for the intended application: the swelling capacity was evaluated, the degradation rate in a simulated physiological environment was assessed, and compression tests were performed. Furthermore, vancomycin was incorporated into the polymeric matrices to obtain scaffolds with antibacterial performance, and their drug release profile was assessed. The cytotoxic profile of the hydrogels was assessed by an MTS assay, using osteoblasts as model cells. The data obtained demonstrated that dextran-based hydrogels were successfully synthesized, with a drug release profile with an initial burst between 50 and 80% of the drug. The hydrogels possess fair biocompatibility. The swelling capacity showed that the stability of the samples and their degradation profile is compatible with the average time period required for bone regeneration (usually about one month) and have a favorable Young's modulus (200-300 kPa). The obtained hydrogels are well-suited for bone regeneration applications such as infections that occur during implantation or bone graft substitutes with antibiotics.

Project description:Directing the organization of cells into a tissue with defined architectures is one use of biomaterials for regenerative medicine. To this end, hydrogels are widely investigated as they have mechanical properties similar to native soft tissues and can be formed in situ to conform to a defect. Herein, we describe the development of porous hydrogel tubes fabricated through a two-step polymerization process with an intermediate microsphere phase that provides macroscale porosity (66.5%) for cell infiltration. These tubes were investigated in a spinal cord injury model, with the tubes assembled to conform to the injury and to provide an orientation that guides axons through the injury. Implanted tubes had good apposition and were integrated with the host tissue due to cell infiltration, with a transient increase in immune cell infiltration at 1 week that resolved by 2 weeks post injury compared to a gelfoam control. The glial scar was significantly reduced relative to control, which enabled robust axon growth along the inner and outer surface of the tubes. Axon density within the hydrogel tubes (1744 axons/mm2) was significantly increased more than 3-fold compared to the control (456 axons/mm2), with approximately 30% of axons within the tube myelinated. Furthermore, implantation of hydrogel tubes enhanced functional recovery relative to control. This modular assembly of porous tubes to fill a defect and directionally orient tissue growth could be extended beyond spinal cord injury to other tissues, such as vascular or musculoskeletal tissue. STATEMENT OF SIGNIFICANCE: Tissue engineering approaches that mimic the native architecture of healthy tissue are needed following injury. Traditionally, pre-molded scaffolds have been implemented but require a priori knowledge of wound geometries. Conversely, hydrogels can conform to any injury, but do not guide bi-directional regeneration. In this work, we investigate the feasibility of a system of modular hydrogel tubes to promote bi-directional regeneration after spinal cord injury. This system allows for tubes to be cut to size during surgery and implanted one-by-one to fill any injury, while providing bi-directional guidance. Moreover, this system of tubes can be broadly applied to tissue engineering approaches that require a modular guidance system, such as repair to vascular or musculoskeletal tissues.

Dataset Information

Contactless magnetically responsive injectable hydrogel for aligned tissue regeneration.

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Contactless magnetically responsive injectable hydrogel for aligned tissue regeneration.

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