Mechanically regulated differentiation of adipose-derived mesenchymal stem cells by PDA-functionalized injectable microgels towards intervertebral disc repair.

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)

Mechanotransduction refers to the cellular mechanism by which mechanical cues from the extracellular matrix (ECM) are sensed and transduced into biochemical signals, playing a critical role in regulating stem cell differentiation. In degenerative intervertebral disc (IVD) disease, the mechanical microenvironment undergoes pathological alterations, most notably a marked increase in ECM stiffness. This aberrant mechanical milieu disrupts cellular fate decisions and poses a critical barrier to successful endogenous regeneration. To address this limitation, poly(acrylamide-co-acrylic acid) (P(AAm-co-AA)) microgels with tunable elastic moduli were synthesized via inverse emulsion polymerization. These microgels were subsequently functionalized with polydopamine (PDA) to enhance cellular adhesion, thereby facilitating cytoskeletal remodeling and activation of mechanotransductive signaling pathways. Notably, a compliant matrix with an elastic modulus of approximately 2 kPa was found to enhance nucleus pulposus (NP)-like differentiation of adipose-derived mesenchymal stem cells in differentiation-inducing medium, as evidenced by significantly upregulated expression of NP marker genes (COL2, ACAN, SOX9). This effect was correlated with the translocation of yes-associated protein 1 (YAP). In vivo studies demonstrated that implantation of these microgels into degenerated discs led to rest

Evidence level

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

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