Non-collagenous proteins, rather than the collagens, are key biochemical factors that mediate tenogenic bioactivity of tendon extracellular matrix.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Despite the growing clinical use of extracellular matrix (ECM)-based biomaterials for tendon repair, undesired healing outcomes or complications have frequently been reported. A major scientific challenge has been the limited understanding of their functional compositions and mechanisms of action due to the complex nature of tendon ECM. Previously, we have reported a soluble ECM fraction from bovine tendons (tECM) by urea extraction, which exhibited strong, pro-tenogenic bioactivity on human adipose-derived stem cells (hASCs). In this study, to advance our previous findings and gain insights into the biochemical nature of its pro-tenogenesis activity, tECM was fractionated using (i) an enzymatic digestion approach (pepsin, hyaluronidase, and chondroitinase) to yield various enzyme-digested tECM fractions; and (ii) a gelation-based approach to yield collagen matrix-enriched (CM) and non-collagenous matrix-enriched (NCM) fractions. Their tenogenic bioactivity on hASCs was assessed. Our results collectively indicated that non-collagenous tECM proteins, rather than collagens, are likely the important biochemical factors responsible for tECM pro-tenogenesis bioactivity. Mechanistically, RNA-seq analysis revealed that tECM and its non-collagenous portion induced similar transcriptional profiles of hASCs, particularly genes associated with cell proliferation, collagen synthesis, and t

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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