An Effective Translation: The Development of Hyaluronan-Based Medical Products From the Physicochemical, and Preclinical Aspects

Abstract

This review shows the steps toward material selection focalized on the design and development of medical devices based on hyaluronan (HA). The selection is based on chemical and mechanical properties, biocompatibility, sterilization, safety, and scale-up costs. These facts play a vital role in the industrialization process. Approved medical devices containing-HA are illustrated to identify key parameters. The first part of this work involves the steps toward a complete characterization of chemical and mechanical aspects, reproducibility of the processes and scale up. In a second stage, we aimed to describe the preclinical in vitro and in vivo assays and selected examples of clinical trials. Furthermore, it is important to keep in mind the regulatory affairs during the research and development (R&D) using standardization (ISO standards) to achieve the main goal, which is the functionality and safety of the final device. To keep reproducible experimental data to prepare an efficient master file for the device, based on quality and recorded manufacturing data, and a rigorous R&D process may help toward clinical translation. A strong debate is still going on because the denominated basic research in HA field does not pay attention to the purity and quality of the raw materials used during the development. So that, to achieve the next generation of devices is needed to overcome the limitations of state of art in terms of efficacy, biodegradability, and non-toxicity.

Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties

“…Our observation that at physiological levels vHMM-HA better protects human cells from stress than the shorter HMM-HA has significant clinical implications considering the broad medical applications of HA 42 . Manufacturing higher molecular mass HA might lead to the improvement of HA-based medical products.…”

Sodium hyaluronate supplemented culture medium combined with joint-simulating mechanical loading improves chondrogenic differentiation of human mesenchymal stem cells

“…However, one of the main challenges of in vitro hBM-MSC chondrogenic differentiation is the lack of a suitable culture environment that reproduces the in vivo physiological conditions and, in so doing, prevents or reduces the progression of MSC-derived chondrocytes through hypertrophic differentiation, www.ecmjournal.org G Monaco et al Role of HA and mechanical load on chondrogenesis exposed to HA contained within the synovial fluid (Kang et al, 2008;Oussedik et al, 2015;Steadman et al, 2001). Therefore, HA has been extensively used as target molecule for scaffold or hydrogel manufacturing, alone or in combination with MSCs, to reproduce engineered cartilage with native structure or to enhance the repair of osteochondral defects (Gallo et al, 2019;Huerta-Ángeles et al, 2018;Li et al, 2018;Radice et al, 2000;Solchaga et al, 2000). However, few studies have described the use of HA as an exogenous medium supplement to promote the chondrogenic differentiation of MSCs (Hegewald et al, 2004;Monaco et al, 2020).…”

Sodium Hyaluronate Supplemented Culture Media as a New hMSC Chondrogenic Differentiation Media-Model for in vitro/ex vivo Screening of Potential Cartilage Repair Therapies

“…HA has been extensively used as a polymer in scaffolds or hydrogel form, alone or in combination with MSCs to produce engineered cartilage with native tissue properties (Radice et al, 2000;Solchaga et al, 2000;Huerta-Ángeles et al, 2018;Li et al, 2018;Gallo et al, 2019).…”