In vivo demonstration of the suitability of piezoelectric stimuli for bone reparation
Graphical abstract
Introduction
Bone is one of the body tissues most often suffering implants [1]. Bone damage or fracture can require bone grafting or the use of bone graft substitutes in order to provide support, promote new bone formation and/or fill the defects [2].
Bone defects are very challenging in orthopedic practice and bone regeneration continues to be a challenge in clinical cases. Thereby, there is a high demand for the development of solutions and/or alternative bone substitutes [3], [4] of both biological and synthetic origin [5]. Synthetic bone substitutes should be biocompatible, show minimal fibrotic reaction, undergo remodeling and support new bone formation [4].
An important characteristic of bone, which has not been enough taken into account for applications, is its piezoelectric nature [6]. This is particularly relevant, as this characteristic can be essential for the development of fully functional bone. In fact, it has been demonstrated that when the bone is mechanically stressed, electrical signals are produced which in turn promote bone growth and remodeling [7]. In this way, being piezoelectricity an essential property of functional bone, two conclusions can be stated: bone substitutes should possess preferably this property and scaffolds for bone regeneration should be preferably piezoelectric [8].
Among piezoelectric materials, polymer based materials have confirmed their suitability for tissue engineering applications [7], being poly(vinylidene fluoride) (PVDF) the biocompatible polymer with the largest piezoelectric response [9]. Further, it has been demonstrated in vitro assays that when PVDF is stimulated mechanically, a transient surface charge is induced and the proliferation and differentiation of pre-osteoblast and human adipose stem cells is enhanced [7]. The in vivo pro-inflammatory effects of PVDF was also evaluated and no significant differences of microvessel density comparing with the control were detected [10]. Further, the material can be prepared in the form of films, fibers, spheres and 3D [11], [12].
However, to our knowledge, no in vivo data are available analyzing the effect of piezoelectric PVDF on bone formation, which is the main goal of the present work.
Section snippets
Materials processing
β-PVDF films poled and non-poled were prepared as described in Ref. [13]. The piezoelectric value (d33) of poled β-PVDF films was ∼−24 pC.N−1 (model 8000, APC Int. Ltd). β-PVDF randomly oriented fibers were also produced accordingly to [13] with a fiber diameter of approximately 500 nm. After electrospinning, the fibers are poled due to the strong electric field of the process, leading to piezoelectric responses around twice the films value [14]. The material properties are presented in Table 1.
Results and discussion
Independently of the implanted material, all the rats completed the experimental period without any complications and no inflammatory reactions or infection around the implanted materials were observed.
The regenerated bone qualification was performed according the H&E staining by the visualization of the obtained images (Fig. 2), which are representative of the cross-section through the entire defect.
After 4 weeks of implantation no bone regeneration or any kind of response is observed when
Conclusions
The potential of piezoelectric biomaterials for bone regeneration has been demonstrated. These findings encourage the development of piezoelectric substitutes in the form of 3D scaffolds and from biodegradable materials for bone tissue engineering in order to reach full therapeutic applicability.
Acknowledgment
The authors thank FEDER funds through the COMPETE 2020 Programme (POCI-01-0145-FEDER-006941) and National Funds through FCT-Portuguese Foundation for Science and Technology: Strategic Funding UID/FIS/04650/2013 and UID/BIM/04293/2013 and grants SFRH/BPD/90870/2012(CR), SFRH/BD/82411/2011(DMC). Funding by the Spanish Ministry of Economy and Competitiveness (MINECO) through the project MAT2016-76039-C4-3-R is acknowledged.
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