Growth factors and mechanical cues synergistically affect cellular functions, triggering a variety of signaling pathways. The molecular levels of such cooperative interactions are not fully understood. Due to its role in osteogenesis, the growth factor bone morphogenetic protein 2 (BMP‐2) is of tremendous interest for bone regenerative medicine, osteoporosis therapeutics, and beyond. Here, contribution of BMP‐2 signaling and extracellular mechanical cues to the osteogenic commitment of C2C12 cells is investigated. It is revealed that these two distinct pathways are integrated at the transcriptional level to provide multifactorial control of cell differentiation. The activation of osteogenic genes requires the cooperation of BMP‐2 pathway‐associated Smad1/5/8 heteromeric complexes and mechanosensitive YAP/TAZ translocation. It is further demonstrated that the Smad complexes remain bound onto and active on target genes, even after BMP‐2 removal, suggesting that they act as a “molecular memory unit.” Thus, synergistic stimulation with BMP‐2 and mechanical cues drives osteogenic differentiation in a programmable fashion.

Recreating the healing microenvironment is essential to regulate cell–material interactions and ensure the integration of biomaterials. To repair bone, such bioactivity can be achieved by mimicking its extracellular matrix (ECM) and by stimulating integrin and growth factor (GF) signaling. However, current approaches relying on the use of GFs, such as bone morphogenetic protein 2 (BMP‐2), entail clinical risks. Here, a biomimetic peptide integrating the RGD cell adhesive sequence and the osteogenic DWIVA motif derived from the wrist epitope of BMP‐2 is presented. The approach offers the advantage of having a spatial control over the single binding of integrins and BMP receptors. Such multifunctional platform is designed to incorporate 3,4‐dihydroxyphenylalanine to bind metallic oxides with high affinity in a one step process. Functionalization of glass substrates with the engineered peptide is characterized by physicochemical methods, proving a successful surface modification. The biomimetic interfaces significantly improve the adhesion of C2C12 cells, inhibit myotube formation, and activate the BMP‐dependent signaling via p38. These effects are not observed on surfaces displaying only one bioactive motif, a mixture of both motifs or soluble DWIVA. These data prove the biological potential of recreating the ECM and engaging in integrin and GF crosstalk via molecular‐based mimics.

The fabrication and optical characterization of self-assembled arrangements of rough gold nanoparticles with a high area coverage and narrow gaps for surface-enhanced Raman spectroscopy (SERS) are reported. A combination of micellar nanolithography and electroless deposition (ED) enables the tuning of the spacing and size of the noble metal nanoparticles. Long-range ordered quasi-hexagonal arrays of gold nanoparticles on silicon substrates with a variation of the particle sizes from about 20 nm to 120 nm are demonstrated. By increasing the particle sizes for the homogeneously spaced particles, a large number of narrow gaps is created, which together with the rough surface of the particles induces a high density of intense hotspots. This makes the surfaces interesting for future applications in near-field-enhanced bio-analytics of molecules. SERS was demonstrated by measuring Raman spectra of 4-MBA on the gold nanoparticles. It was verified that a smaller inter-particle distance leads to an increased SERS signal.

Stimulating integrin and growth factor signaling is a major goal to regulate cell‐material interactions. This cover shows a biomimetic peptide containing the RGD cell adhesive motif and the osteogenic DWIVA sequence anchored to a glass model substrate. This work can be found in article number 2001757 by Carlos Mas‐Moruno and co‐workers. Such functionalized surface fine‐tuned the behavior of C2C12 cells in a synergistic manner.