Design and clinical application of injectable hydrogels for musculoskeletal therapy

Abstract

Musculoskeletal defects are an enormous healthcare burden and source of pain and disability for individuals. With an aging population, the proportion of individuals living with these medical indications will increase. Simultaneously, there is pressure on healthcare providers to source efficient solutions, which are cheaper and less invasive than conventional technology. This has led to an increased research focus on hydrogels as highly biocompatible biomaterials that can be delivered through minimally invasive procedures. This review will discuss how hydrogels can be designed for clinical translation, particularly in the context of the new European Medical Device Regulation (MDR). We will then do a deep dive into the clinically used hydrogel solutions that have been commercially approved or have undergone clinical trials in Europe or the United States. We will discuss the therapeutic mechanism and limitations of these products. Due to the vast application areas of hydrogels, this work focuses only on treatments of cartilage, bone, and the nucleus pulposus. Lastly, the main steps toward clinical translation of hydrogels as medical devices are outlined. We suggest a framework for how academics can assist small and medium MedTech enterprises conducting the initial clinical investigation and post‐market clinical follow‐up required in the MDR. It is evident that the successful translation of hydrogels is governed by acquiring high‐quality pre‐clinical and clinical data confirming the device mechanism of action and safety.

Self-Healing Injectable Hydrogels for Tissue Regeneration

“…For instance, soft hydrogels have been found to promote adipogenesis, while stiffer hydrogels induce osteogenesis of stem cells. , Hydrogels are also increasingly designed to specifically recruit local immune cells and exert immunomodulatory effects, e.g., for cancer immunotherapy. − There are many self-healing injectable hydrogel formulations currently at a preclinical or clinical stage. Interesting perspectives how to foster their translation are provided by Correa et al and Øvrebø et al…”

“…Interesting perspectives how to foster their translation are provided by Correa et al 16 and Øvrebø et al 345 To conclude, self-healing injectable hydrogels may be exploited for several tissue regeneration strategies, either as "empty" hydrogels for mechanical support, for controlled delivery of drugs or cells, for repeated localized radiation therapy, or for local cell recruitment. A schematic overview of tissue regeneration strategies using self-healing injectable hydrogels is provided in Figure 7.…”

Injectable and Self-Invigorating Hydrogel Applications in Dentistry and Periodontal Regeneration: A Literature Review

“…Emdogain is based on a derivative of porcine enamel matrix, a combination of proteins supplied in an aqueous gel solution made of propylene glycol alginate and including amelogenin (90%) along with a few other nanomelogenin such as ameloblastin, enamelin, and tuftelin. Emdogain has been shown to regenerate a variety of periodontal tissues, including connective tissues like the periodontal ligament as well as osseo-like tissues, acellular cementum, and alveolar bone [ 31 ]. Aspirin/erythropoietin was used to fill the successfully created and proven to be helpful in periodontium regeneration CS/gelatin hydrogel [ 32 ].…”

Polymer-based thermoresponsive hydrogels for controlled drug delivery

“…Hydrogels are three-dimensional structure of polymeric networks able to swell in the presence of a water solution [1][2][3][4][5]. Thanks to their ability of containing a large quantity of water and physiological fluids, they are highly biocompatible and able to mimic the biological tissue [6][7][8].…”