International Journal of Nanomedicine (Jul 2019)
Enhancement of bone consolidation using high-frequency pulsed electromagnetic short-waves and titanium implants coated with biomimetic composite embedded into PLA matrix: in vivo evaluation
Abstract
Daniel Oltean-Dan,1 Gabriela-Bombonica Dogaru,2 Maria Tomoaia-Cotisel,3,4 Dragos Apostu,1 Alexandru Mester,5 Horea-Rares-Ciprian Benea,1 Mihai-Gheorghe Paiusan,1 Elena-Mihaela Jianu,6 Aurora Mocanu,3 Reka Balint,3 Catalin-Ovidiu Popa,7 Cristian Berce,8 Gyorgy-Istvan Bodizs,9 Alina-Mihaela Toader,10 Gheorghe Tomoaia1,41Iuliu Hatieganu University of Medicine and Pharmacy, Department of Orthopedics and Traumatology, 400132 Cluj-Napoca, Romania; 2Iuliu Hatieganu University of Medicine and Pharmacy, Department of Medical Rehabilitation, 400347 Cluj-Napoca, Romania; 3Babes Bolyai University, Faculty of Chemistry and Chemical Engineering, Department of Chemical Engineering, Research Center of Physical Chemistry, 400028 Cluj-Napoca, Romania; 4Academy of Romanian Scientists, 050085 Bucharest, Romania; 5Iuliu Hatieganu University of Medicine and Pharmacy, Department of Oral Rehabilitation, Oral Health and Management, 400012 Cluj-Napoca, Romania; 6Iuliu Hatieganu University of Medicine and Pharmacy, Department of Histology, 400349 Cluj-Napoca, Romania; 7Technical University of Cluj-Napoca, Department of Materials Science and Engineering, 400641 Cluj-Napoca, Romania; 8Iuliu Hatieganu University of Medicine and Pharmacy, Center for Experimental Medicine, 400349 Cluj-Napoca, Romania; 9Rehabilitation Clinic, 400347 Cluj-Napoca, Romania; 10Iuliu Hatieganu University of Medicine and Pharmacy, Department of Physiology, 400006 Cluj-Napoca, RomaniaPurpose: Bone consolidation after severe trauma is the most challenging task in orthopedic surgery. This study aimed to develop biomimetic composite for coating Ti implants. Afterwards, these implants were tested in vivo to assess bone consolidation in the absence or the presence of high-frequency pulsed electromagnetic short-waves (HF-PESW).Materials: Biomimetic coating was successfully developed using multi-substituted hydroxyapatite (ms-HAP) functionalized with collagen (ms-HAP/COL), embedded into poly-lactic acid (PLA) matrix (ms-HAP/COL@PLA), and subsequently covered with self-assembled COL layer (ms-HAP/COL@PLA/COL, named HAPc).Methods: For in vivo evaluation, 32 Wistar albino rats were used in four groups: control group (CG) with Ti implant; PESW group with Ti implant+HF-PESW; HAPc group with Ti implant coated with HAPc; HAPc+PESW group with Ti implant coated with HAPc+HF-PESW. Left femoral diaphysis was fractured and fixed intramedullary. From the first post-operative day, PESW and HAPc+PESW groups underwent HF-PESW stimulation for 14 consecutive days. Biomimetic coating was characterized by XRD, HR-TEM, SEM, EDX and AFM.Results: Osteogenic markers (ALP and osteocalcin) and micro-computed tomography (CT) analysis (especially bone volume/tissue volume ratio results) indicated at 2 weeks the following group order: HAPc+PESW>HAPc≈PESW (P>0.05) and HAPc+PESW>control (P<0.05), indicating the higher values in HAPc+PESW group compared to CG. The fracture-site bone strength showed, at 2 weeks, the highest average value in HAPc+PESW group. Moreover, histological analysis revealed the most abundant COL fibers assembled in dense bundles in HAPc-PESW group. At 8 weeks, micro-CT indicated higher values only in HAPc+PESW group vs CG (P<0.05), and histological results showed a complete-healed fracture in groups: HAPc+PESW, HAPc and PESW, but with more advanced bone remodeling in HAPc+PESW group.Conclusion: Using Ti implants coated by HAPc jointly with HF-PESW stimulation positively influenced the bone consolidation process, especially in its early phase, thus potentially providing a superior strategy for clinical applications.Keywords: fracture healing, HF-PESW, titanium implants, biomimetic composite coating, multi-substituted hydroxyapatite, collagen fibers
