Osteogenic and Biocompatibility Potential of Polylactic Acid-Based Materials: A Systematic Review of Human Primary Cells Studies

Background: Guided Bone Regeneration (GBR) relies on barrier membranes, for which polylactic acid (PLA) and its copolymer poly(lactic-co-glycolic acid) (PLGA) are promising biodegradable polymers. However, their inherent hydrophobicity limits biological performance, and the evidence regarding how specific modifications affect key human cell types, particularly osteoblasts and fibroblasts, remains scattered. Methods: A systematic review was conducted to synthesize the in vitro evidence on the response of primary human osteoblasts and fibroblasts to polylactic acid-based materials. Following a pre-registered protocol (10.17605/OSF.IO/CE8KB), a comprehensive search was performed across four major databases, and the risk of bias in the included studies was assessed using an adapted OHAT tool. Results: Twenty-six studies were included, which showed that polylactic acid-based materials have limited bioactivity, and their modification significantly improves cellular responses. The incorporation of bioceramics and growth factors, or alterations in surface topography, notably enhanced osteogenic differentiation and mineralization in osteoblasts. For gingival fibroblasts, topographical modifications like micro-grooves guided cell alignment and modulated proliferation. Conclusions: Native polylactic acid-based materials display limited bioactivity. However, functionalization through bioceramics incorporation, growth factor delivery, and surface topographical modification is crucial for transforming them into bioactive scaffolds capable of achieving the dual biofunctionality required for successful GBR.