Graphical abstract

Biophysical properties of the extracellular environment dynamically regulate cellular fates. In this review, we highlight silk, an indispensable polymeric biomaterial, owing to its unique mechanical properties, bioactive component sequestration, degradability, well-defined architectures, and biocompatibility that can regulate temporospatial biochemical and biophysical responses. We explore how the materiobiology of silks, both mulberry and non-mulberry based, affect cell behaviors including cell adhesion, cell proliferation, cell migration, and cell differentiation. Keeping in mind the novel biophysical properties of silk in film, fiber, or sponge forms, coupled with facile chemical decoration, and its ability to match functional requirements for specific tissues, we survey the influence of composition, mechanical properties, topography, and 3D geometry in unlocking the body’s inherent regenerative potential.

Graphene quantum dots (GQDs) are the harbingers of a paradigm shift that revitalize self-assembly of the colloidal puzzle by adding shape and size to the material-design palette. Although self-assembly is ubiquitous in nature, the extent to which these molecular legos can be engineered reminds us that we are still apprenticing polymer carpenters. In this quest to unlock exotic nanostructures ascending from eventual anisotropy, we have utilized different concentrations of GQDs as a filler in free-radical-mediated aqueous copolymerization. Extensive polymer grafting over the geometrically confined landscape of GQDs (0.05%) bolsters crystallization instilling a loom which steers interaction of polymeric cilia into interlaced equilateral triangles with high sophistication. Such two-dimensional (2D) assemblies epitomizing the planar tiling of “Star of David” forming a molecular kagome lattice (KL) without metal templation evoke petrichor. Interestingly, a higher percentage (0.3%) of GQDs allow selective tuning of the interfacial property of copolymers breaking symmetry due to surface energy incongruity, producing exotic Janus nanomicelles (JNMs). Herein, with the help of a suite of characterizations, we delineate the mechanism behind the formation of the KL and JNMs which forms a depot of heightened drug accretion with targeted delivery of 5-fluorouracil in the colon as validated by gamma scintigraphy studies.

Graphitic carbon nitride (gCN) has only recently experienced a renaissance in a myriad of domains despite existing as a long-established material described in the chemical literature. Notwithstanding the upturn, their conventional synthesis at extremely high temperatures yielding limiting compositions stands in the way of achieving a paradigm shift in gCN fabrication. With the ultimate goal of surpassing these hurdles, we utilize Ndoped carbon nanosheets (N-CNS) as a filler in free-radical-mediated aqueous copolymerization. By dispersing N-CNS in a polymer matrix, high-performance mechanically robust composites could be developed and tailored to individual applications. As-synthesized hydrogel nanocomposite systems are used to decode the balance for emulating evolutionary accomplishments of nature's nanocomposites like the "abalone's nacre". At a lower concentration (0.05%), N-CNS disperse homogeneously and interact intimately with the polymer matrix forming an "interphase" zone around individual nanofillers dramatically affecting the mobility of polymer chains to yield sheet architectures. On increasing the filler concentration (0.3%), the intercalation phenomenon gets perturbed due to an intrinsically oriented aggregation of nanofiller giving rise to a surge in entropy that leads to conspicuous buckling and tubular aggregates. At the interfacial regime, the poly(acrylic acid) domains come in closer proximity to the hydrophobic cages of N-CNS, and a nanoconfinement effect exerts high pressure manifesting acid-catalyzed condensation of melamine units to form, for the first time, quasi-two-dimensional heptazine-gCN (h-gCN) within hydrogel nanocomposites. Polymer properties are enhanced by the addition of N-CNS through complex interfacial interactions and the unique distributions of internanofiller distances. Endowed with mechanical properties that closely mimic natural skin and combined with the repurposed drug "losartan", these hydrogel nanocomposites offer scarless healing of second-degree burns.

Nanoconfinement within flexible interfaces is a key step towards exploiting confinement effects in several biological and technological systems wherein flexible 2D materials are frequently utilized but are arduous to prepare. Hitherto unreported, the synthesis of 2D Hydrogel nanosheets (HNS) using a template- and catalyst-free process is developed representing a fertile ground for fundamental structure-property investigations. In due course of time, nucleating folds propagating along the edges trigger co-operative deformations of HNS generating regions of nanoconfinement within trapped water islands. These severely constricting surfaces force water molecules to pack within the nanoscale regime of HNS almost parallel to the surface bringing about phase transition into puckered rhombic ice with AA and AB Bernal stacking pattern, which was mostly restricted to Molecular dynamics (MD) studies so far. Interestingly, under high lateral pressure and spatial inhomogeneity within nanoscale confinement, bilayer rhombic ice structures were formed with an in-plane lattice spacing of 0.31 nm. In this work, a systematic exploration of rhombic ice formation within HNS has been delineated using High-resolution transmission electron microscopy (HRTEM), and its ultrathin morphology was examined using Atomic Force Microscopy (AFM). Scanning Electron Microscopy (SEM) images revealed high porosity while mechanical testing presented young’s modulus of 155 kPa with ~84% deformation, whereas contact angle suggested high hydrophilicity. The combinations of nanosheets, porosity, nanoconfinement, hydrophilicity, and mechanical strength, motivated us to explore their application as a scaffold for cartilage regeneration, by inducing chondrogenesis of human Wharton Jelly derived mesenchymal stem cells (hWJ MSCs). HNS promoted the formation of cell aggregates giving higher number of spheroid formation and a marked expression of chondrogenic markers (ColI, ColII, ColX, ACAN and S-100), thereby providing some cues for guiding chondrogenic differentiation.