Ti-Based Template Incorporated with RGD Amino Motif as a Domain Supporting Self-Assembly of Extracellular Matrix in Bone Tissue Regeneration: Preparation, Characterization, and Correlated Structure to Identified Application

Bone tissue engineering utilizing bioactive materials represents a promising strategy for regenerating bone defects and stimulating new tissue growth. In this study, a biocompatible, bone-mimicking material was developed by incorporating the arginine–glycine–aspartate (RGD) amino motif onto the surface of a titanium-based metal–organic framework (MOF), MIL-125, using a simple solvent-soaking method to impart osteoinductive properties. The molecular incorporation, phase composition, and surface morphology of the functionalized MIL-125 powder were comprehensively characterized using microdifferential scanning calorimetry (Micro-DSC), XRD, SEM, EDX, and FT-IR. Among the investigated conditions, the MIL-125 sample prepared with 0.25 mg of RGD and a 36 h soaking time exhibited the most favorable physicochemical characteristics based on the combined structural, spectroscopic, thermal, elemental, and morphological analyses. SEM analysis revealed the initial development of needle-like RGD-associated structures at 0.15 mg of RGD, which was consistent with the appearance of an exothermic Micro-DSC peak associated with RGD interaction with the MIL-125 surface. Furthermore, quantum chemical calculations were performed to elucidate the molecular-level interaction mechanisms between the peptide and the MOF framework. The computational results uncovered two stable adsorption configurations within the MIL-125 pore structure. Among these, the aspartic acid (ASP)-terminal-coordinated titanium oxide cluster of MIL-125 exhibited the highest thermodynamic stability, possessing an adsorption energy of −24.99 kcal/mol, which was more than 2-fold stronger than the arginine (ARG)-terminal interaction. This strong electronic binding corroborates the experimentally observed RGD immobilization. Ultimately, these fundamental insights into RGD–MOF chemical interactions provide a robust framework for developing advanced bioactive components suitable for orthopedic regeneration applications.