Tunable piezoelectric PLLA nanofiber membranes for enhanced mandibular repair with optimal self-powering stimulation

Abstract Poly (l-lactic acid) (PLLA) is a biocompatible, biodegradable material with piezoelectric properties, making it a promising candidate for providing self-powered stimulation to accelerate tissue repair. Repairs to various tissues, such as bone, cartilage and nerve, necessitate distinct piezoelectric characteristics even from the same material. However, the extensive utilization of PLLA piezoelectric scaffolds in various tissue is hindered by their low and single piezoelectric constants. In this study, PLLA nanofiber membranes with enhanced and adjustable piezoelectric constants (d33) were fabricated through oriented electrospinning. By carefully controlling the parameters of the spinning solution, a steady increase in d33 values from 0 to 30 pC/N was achieved. This advancement allows tailoring of PLLA nanofiber membranes to meet various piezoelectric requirements of different tissues. As an example of tailoring the optimal piezoelectric constants, we developed PLLA-2-0, PLLA-2-10, PLLA-2-15 and PLLA-2-20 nanofiber membranes with d33 values of 0, 5, 10 and 15 pC/N, respectively. The impact of varying piezoelectric constants of PLLA nanofiber membranes on cellular behavior and repair efficacy were validated through in vitro cellular experiments and in vivo mandibular critical defect repair. The results indicated that PLLA-2-20 demonstrated superior cell proliferation rate up to 130% and an osteogenic differentiation level approximately twice of the control. In addition, PLLA-2-20 significantly promoted cell adhesion and migration, and the cell aspect ratio was about five times higher than that of the control group. In vivo, PLLA-2-20 optimal restorative effects on rat mandibles via endogenous mechanical force-mediated piezoelectric stimulation, leading to complete histological restoration within 8 weeks. These findings highlight the potential of the PLLA membranes with high and adjustable d33 by a straightforward process. This study provides a novel approach for the development of highly electroactive membranes tailored to specific tissue repair needs.