Musculoskeletal tissues-on-a-chip: role of natural polymers in reproducing tissue-specific microenvironments

Abstract

Over the past years, 3D in vitro models have been widely employed in the regenerative medicine field. Among them, organ-on-a-chip technology has the potential to elucidate cellular mechanism exploiting multichannel microfluidic devices to establish 3D co-culture systems that offer control over the cellular, physico-chemical and biochemical microenvironments. To deliver the most relevant cues to cells, it is of paramount importance to select the most appropriate matrix for mimicking the extracellular matrix of the native tissue. Natural polymers-based hydrogels are the elected candidates for reproducing tissue-specific microenvironments in musculoskeletal tissue-on-a-chip models owning to their interesting and peculiar physico-chemical, mechanical and biological properties. Despite these advantages, there is still a gap between the biomaterials complexity in conventional tissue engineering and the application of these biomaterials in 3D in vitro microfluidic models. In this review, the aim is to suggest the adoption of more suitable biomaterials, alternative crosslinking strategies and tissue engineered-inspired approaches in organ-on-a-chip to better mimic the complexity of physiological musculoskeletal tissues. Accordingly, after giving an overview of the musculoskeletal tissue compositions, the properties of the main natural polymers employed in microfluidic systems are investigated, together with the main musculoskeletal tissues-on-a-chip devices.

Bioactive Composite Methacrylated Gellan Gum for 3D-Printed Bone Tissue-Engineered Scaffolds

“…The inherent structural similarities to native glycosaminoglycans and, hence, the proven biocompatibility, along with the mild processing conditions for scaffold fabrication, have made GG-derivatives suitable for tissue engineering applications [ 51 ]. The properties of GG-derivatives, such as mechanical stability, flexibility and responsiveness to external stimuli, have been improved and tailored by introducing bioactive moieties including nanoparticles and bioactive compounds [ 6 ]. Therefore, this work aimed to study the effect of BSF-Eumel and HAp as bioactive signals in triggering a physiological response in 7F2 osteoblastic cells when seeded on a 3D-printed GGMA-based scaffold.…”

“…Therefore, the natural polymers’ printing fidelity in layer-by-layer approaches is not fully ensured; hence the need to be functionalized. Indeed, the introduction of suitable functional groups (i.e., by esterification, aminated carboxymethylation or methacrylation) may improve the mechanical stability after printing as well as the physico-chemical properties (i.e., residence time and swelling) of the final structure [ 5 , 6 , 7 , 8 , 9 ].…”

Understanding Atherosclerosis Pathophysiology: Can Additive Manufacturing Be Helpful?

“…Table 5 summarizes the most used materials in 3D printing of blood vessels, although most of the works do not specify the chemistry of the polymeric material. Moreover, some critical reviews on 3D printing and polymers to reproduce biological tissues environments can also be consulted, such as those of references [ 74 , 75 ].…”

Eumelanin from the Black Soldier Fly as Sustainable Biomaterial: Characterisation and Functional Benefits in Tissue-Engineered Composite Scaffolds

“…Inspired by this application, a hyaluronic acid sodium salt with high molecular weight (HM w HAs)-based matrix was selected for the 3D printing of a bone tissue-engineered scaffold in which BSF-Eumel was supposed to exert a bioactive stimulus. HA [α-1,4-D-glucuronic acid-β-1,3-N-acetyl-D-glucosamine] n is a naturally occurring hydrophilic glycosaminoglycan whose chemical structure may allow easy chemical modification of the hydroxyl groups by esterification [ 22 , 23 ]. Indeed, modification with methacrylate groups can allow the crosslinking by UV light, in the presence of a photoinitiator.…”