Development and Characterization of Polycaprolactone Scaffolds Functionalized with Nano-Hydroxyapatite to Enhance Osteogenic Potential

Nanotechnology has revolutionized the field of regenerative medicine, enabling the creation of biomaterials capable of interacting with living tissues at the molecular and cellular level. Within this framework, bone tissue engineering has emerged as one of the most promising applications, offering innovative alternatives to traditional grafts for the repair of complex bone defects. The present doctoral research aimed to develop, characterize, and biologically validate a new generation of bioactive scaffolds based on polycaprolactone (PCL), functionalized with nano-hydroxyapatite (nHAp) and further modified through plasma activation, ultraviolet (UV) crosslinking, and silver (Ag) doping to enhance osteogenic and antibacterial potential. The study employed a multidisciplinary workflow integrating materials science, nanotechnology, and biological evaluation. PCL scaffolds were fabricated via Fused Deposition Modeling (FDM) using a controlled lattice design to ensure uniform porosity and mechanical integrity. Plasma surface activation introduced polar functional groups that significantly improved surface hydrophilicity, while subsequent coating with nHAp enabled nanoscale mineralization mimicking the inorganic phase of bone. UV irradiation promoted interfacial stability through photochemical crosslinking, and silver ion doping imparted controlled antibacterial functionality. The resulting hierarchical surface architecture was analyzed through a comprehensive suite of morphological, chemical, mechanical, and thermal techniques, including Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Energy Dispersive X-ray Spectroscopy (EDS), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Thermogravimetric Analysis (TGA). Finite Element Modeling (FEM) further validated mechanical performance under simulated loading conditions. Experimental results demonstrated that plasma and nHAp functionalization markedly increased surface roughness, surface energy, and Ca/P stability, promoting enhanced protein adsorption and cell anchorage. Mechanical analyses confirmed the structural reliability of the scaffolds after six months of aging in aqueous and simulated body environments, with stable or slightly improved elastic modulus due to secondary crystallization. Thermal and spectroscopic data validated the chemical stability and homogeneous integration of the nano-coating. Biological assays using human MG63 osteoblast-like cells, murine 3T3 fibroblasts, and MC3T3-E1 pre-osteoblasts confirmed the biocompatibility and osteoconductive nature of the scaffolds, while silver-doped composites exhibited potent antibacterial efficacy without cytotoxic effects. The overall findings highlight the success of a multi-step nanoscale functionalization strategy that transforms a bioinert polymer into a bioactive, osteoconductive, and antimicrobial platform suitable for bone regeneration. By bridging nanostructural design with cellular response, this research contributes to the development of clinically translatable scaffolds for oral and maxillofacial surgery, where infection control and rapid osteointegration are critical. The study underscores how nano-engineering, surface chemistry, and additive manufacturing can converge to create the next generation of intelligent biomaterials for regenerative medicine.

Nanotechnology has revolutionized the field of regenerative medicine, enabling the creation of biomaterials capable of interacting with living tissues at the molecular and cellular level. Within this framework, bone tissue engineering has emerged as one of the most promising applications, offering innovative alternatives to traditional grafts for the repair of complex bone defects. The present doctoral research aimed to develop, characterize, and biologically validate a new generation of bioactive scaffolds based on polycaprolactone (PCL), functionalized with nano-hydroxyapatite (nHAp) and further modified through plasma activation, ultraviolet (UV) crosslinking, and silver (Ag) doping to enhance osteogenic and antibacterial potential. The study employed a multidisciplinary workflow integrating materials science, nanotechnology, and biological evaluation. PCL scaffolds were fabricated via Fused Deposition Modeling (FDM) using a controlled lattice design to ensure uniform porosity and mechanical integrity. Plasma surface activation introduced polar functional groups that significantly improved surface hydrophilicity, while subsequent coating with nHAp enabled nanoscale mineralization mimicking the inorganic phase of bone. UV irradiation promoted interfacial stability through photochemical crosslinking, and silver ion doping imparted controlled antibacterial functionality. The resulting hierarchical surface architecture was analyzed through a comprehensive suite of morphological, chemical, mechanical, and thermal techniques, including Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Energy Dispersive X-ray Spectroscopy (EDS), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Thermogravimetric Analysis (TGA). Finite Element Modeling (FEM) further validated mechanical performance under simulated loading conditions. Experimental results demonstrated that plasma and nHAp functionalization markedly increased surface roughness, surface energy, and Ca/P stability, promoting enhanced protein adsorption and cell anchorage. Mechanical analyses confirmed the structural reliability of the scaffolds after six months of aging in aqueous and simulated body environments, with stable or slightly improved elastic modulus due to secondary crystallization. Thermal and spectroscopic data validated the chemical stability and homogeneous integration of the nano-coating. Biological assays using human MG63 osteoblast-like cells, murine 3T3 fibroblasts, and MC3T3-E1 pre-osteoblasts confirmed the biocompatibility and osteoconductive nature of the scaffolds, while silver-doped composites exhibited potent antibacterial efficacy without cytotoxic effects. The overall findings highlight the success of a multi-step nanoscale functionalization strategy that transforms a bioinert polymer into a bioactive, osteoconductive, and antimicrobial platform suitable for bone regeneration. By bridging nanostructural design with cellular response, this research contributes to the development of clinically translatable scaffolds for oral and maxillofacial surgery, where infection control and rapid osteointegration are critical. The study underscores how nano-engineering, surface chemistry, and additive manufacturing can converge to create the next generation of intelligent biomaterials for regenerative medicine.