The Collagen-Based Medical Device MD-Tissue Acts as a Mechanical Scaffold Influencing Morpho-Functional Properties of Cultured Human Tenocytes

Abstract

Mechanotransduction is the ability of cells to translate mechanical stimuli into biochemical signals that can ultimately influence gene expression, cell morphology and cell fate. Tenocytes are responsible for tendon mechanical adaptation converting mechanical stimuli imposed during mechanical loading, thus affecting extracellular matrix homeostasis. Since we previously demonstrated that MD-Tissue, an injectable collagen-based medical compound containing swine-derived collagen as the main component, is able to affect tenocyte properties, the aim of this study was to analyze whether the effects triggered by MD-Tissue were based on mechanotransduction-related mechanisms. For this purpose, MD-Tissue was used to coat Petri dishes and cytochalasin B was used to deprive tenocytes of mechanical stimulation mediated by the actin cytoskeleton. Cell morphology, migration, collagen turnover pathways and the expression of key mechanosensors were analyzed by morphological and molecular methods. Our findings confirm that MD-Tissue affects collagen turnover pathways and favors cell migration and show that the MD-Tissue-induced effect represents a mechanical input involving the mechanotransduction machinery. Overall, MD-Tissue, acting as a mechanical scaffold, could represent an effective medical device for a novel therapeutic, regenerative and rehabilitative approach to favor tendon healing in tendinopathies.

Morpho-Functional Effect of a New Collagen-Based Medical Device on Human Gingival Fibroblasts: An In Vitro Study

“…These data were in line with previously published data, which, using the same collagen-based injectable medical device as a coating, demonstrated increased viability and substrate attachment of human tenocytes, known specialized fibroblasts of tendons [ 39 , 40 ]. On the contrary, other authors have found no advantages in the use of a collagen coating, demonstrating that fibroblasts (in this case human skin fibroblasts), grown on collagen-coated dishes, were rounder in shape and with a shorter perimeter, compared to those grown on uncoated polystyrene or glass culture dishes [ 50 ].…”

“…On the contrary, other authors have found no advantages in the use of a collagen coating, demonstrating that fibroblasts (in this case human skin fibroblasts), grown on collagen-coated dishes, were rounder in shape and with a shorter perimeter, compared to those grown on uncoated polystyrene or glass culture dishes [ 50 ]. Furthermore, the number and density of cells at confluence were not affected by that specific collagen coating as well, but it should be probably considered that the fibroblast’s origin and the type of collagen used for their experimentation were different from those used in the present study and in the study conducted by Randelli et al [ 40 ].…”

“…This is an injectable medical device composed of collagen type I of porcine origin as the main constituent and excipients such as ascorbic acid, magnesium gluconate, pyridoxine hydrochloride, riboflavin, thiamine hydrochloride, NaCl, and water for injection. Based on the results obtained by Randelli et al [ 39 , 40 ] on human tenocytes, in this study, we hypothesized that allowing hGF to grow on a coating layer made up of this collagen compound could represent a substrate for cell cultures, contributing to their mechanical stimulation and influencing their proliferation and migration properties.…”

“…Interestingly, Dental SKIN BioRegulation (Guna S.p.a., Milan, Italy) has been designed to help counteract the physiological aging of connective tissues and intended to act as a mechanical bio-scaffold, providing physical and chemical support to collagen fibers present in the soft tissues around teeth. In particular, following in the footsteps of the present study design, it was previously demonstrated that this medical device,,though mentioned with another commercial name and tested on specialized fibroblasts in tendon connective tissue (human tenocytes), not only induced type I collagen secretion and increased the levels of Tissue Inhibitor of Matrix Metalloproteinases (TIMP-1), suggesting an anti-collagenolytic effect, but also upregulated the expression of focal adhesions and mechanosensors (FAK, YAP/TAZ), implying a mechanical input for cell migration [ 39 , 40 ]. Clinical studies also corroborated these data, demonstrating that the collagen-based medical compound was effective in connective tissue repair, even in osteoarticular pathologies [ 41 , 42 , 43 , 44 ].…”

Recovery of Bioactive Compounds from Marine Organisms: Focus on the Future Perspectives for Pharmacological, Biomedical and Regenerative Medicine Applications of Marine Collagen

“…In addition to being the main structural element of the extracellular matrix of human tissues, type I collagen also has numerous intrinsic properties, such as biocompatibility for many biological applications, bioactivity, biodegradability, and the ability, in its native form, to generate hydrogels, by a simple pH change [ 41 , 42 , 43 , 44 , 45 , 46 ]. Due to these important characteristics, it receives great attention in the biomedical field, both as a functional ingredient in different formulations and as a component of several products, such as medical devices and pharmaceutical systems [ 46 , 47 , 48 , 49 ]. Although collagen appeared in the first phase of evolution in primitive animals such as jellyfish, corals and sea anemones, the mammalian (especially bovine and porcine) form is the main source used in the industrial and biomedical fields [ 50 , 51 , 52 ].…”