Composite Nanoarchitectonics with Turmeric-Functionalized Layered Double Hydroxide/Poly(3-hydroxyoctanoate) as Bioactive Coatings for Bone and Nerve Regeneration

The limited regenerative capacity of bone and peripheral nerve tissues, together with the insufficient bioactivity and immunomodulatory control of commercially available coating materials, drives the development of multifunctional biomaterials capable of modulating cellular and immune responses. Herein, bacterially derived poly(3-hydroxyoctanoate) (P(3HO)) was applied as a biodegradable matrix for nanocomposites incorporating layered double hydroxides (LDHs) and their turmeric (turm)-functionalized counterparts. Nanocomposite films containing 2 wt.% nanofillers were fabricated by solvent casting. Structural and physicochemical analyses confirmed successful functionalization (up to 60 wt.% turm), with a tendency to form microscale agglomerates within the polymer matrix. These agglomerates contributed to heterogeneous surface topography (R a 0.9–7.9 μm) and governed the structure–property relationship in accordance with the Nanoarchitectonics strategy. Mechanical and surface properties were tunable, especially with a reduction in surface free energy of up to 24% for turm-containing nanocomposites. In vitro studies performed on mouse preosteoblastic (MC3T3-E1) and mouse neuroblastoma × rat glioma hybrid neuronal (NG108-15) cell lines confirmed a lack of toxicity, with cell viability exceeding 70% under both indirect and direct test conditions. All turm-functionalized materials supported cell differentiation and proliferation. However, the most favorable biological response was observed for P(3HO)_Zn/Al-turm, which exhibited enhanced neuronal proliferation of NG108-15 cells. Moreover, this system demonstrated robust immunomodulatory activity, inducing TGF-β1 secretion at ∼1787 pg mL –1 (comparable to the M2 phenotype) while maintaining controlled MMP-2 levels (∼19.9 pg mL –1 ) for human monocytic-derived macrophages (THP-1). In contrast, Ca/Al-based nanocomposites promoted osteogenic responses in MC3T3-E1 cells but showed lower neuronal proliferation. Importantly, incorporation of nanofillers overcame the intrinsic limitations of neat P(3HO), enabling neuronal growth and differentiation. These findings demonstrate that turm-functionalized P(3HO)/LDHs nanocomposites, designed according to the nanoarchitectonics concept, constitute a versatile platform integrating structural tunability and bioactive immunoregulation, opening remarkable perspectives for advanced coatings targeting bone and nerve tissue regeneration.