Modified triple Kessler with least risk of elongation among Achilles tendon repair techniques: a systematic review and network meta-analysis of human cadaveric studies.

PURPOSE: Current treatment recommendations emphasize early loading, with preservation of tendon length and physiologic tension. The objective of this systematic review and network meta-analysis was to compare failure load and elongation after cyclic loading of Achilles tendon repair techniques at time-zero. METHODS: The databases PubMed, CENTRAL and Web of Science were searched for all published in-vitro studies comparing Achilles tendon repair techniques, or augmentation with autografts/biomaterials, and reports of failure load or elongation after cyclic loading. Only studies using human cadaveric Achilles tendons and matched pairs, or randomized specimen allocation, were selected for quantitative synthesis. A network meta-analysis per primary outcome was performed. Results were summarized as P score rankings and their validity was assessed using statistical methods. RESULTS: Sixteen studies, comprising 367 tendon repairs, were included. The following repair techniques were used (n = number of studies): Krackow (n = 8), Achillon (n = 4), double Krackow (n = 3), Bunnell (n = 3), Percutaneous Achilles Repair System (n = 3), Percutaneous Achilles Repair System Midsubstance (n = 2), Kessler (n = 3), double Kessler (n = 1), modified triple Kessler (n = 1), triple bundle (n = 1), a multifilament stainless steel cable-crimp technique (n = 1) and a double loop knot stitch (n = 1). Five studies assessed augmentation with autografts/biomaterials. Regarding the failure load, biomaterial augmented Krackow repairs occupied the first four positions in the ranking, followed by the multifilament stainless steel cable-crimp and Percutaneous Achilles Repair System Midsubstance techniques. Concerning elongation after cyclic loading, the triple Kessler was ranked first, followed by the Achillon and Percutaneous Achilles Repair System Midsubstance techniques. A negligible correlation between ranks was found (rs = 0.11; p = 0.75n.s.), meaning that a higher repair tensile strength is not necessarily related to improved performance in regard to avoidance of elongation. CONCLUSION: In the failure load network meta-analysis, biomaterial augmented Krackow repairs ranked highest, but noticeable statistical heterogeneity was found. Regarding elongation with cyclic loading, the modified triple Kessler stitch showed the highest probability of ranking first. LEVEL OF EVIDENCE: Level IV.

Electronic to ionic transduction of the electric field applied to PEDOT:PSS substrates to the cell cultures on top.

The potential of the electrical double layer (EDL) formed at the interface between cross-linked poly (3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) and phosphate-buffered saline (PBS) was measured with respect to a reference Ag/AgCl electrode, yielding a value of ca. 300 mV, which corresponds to a work function of 4.9 eV. More importantly, we report that the application of a voltage along the PEDOT:PSS substrate induces a modification of the EDL, which mirrors the potential applied to the PEDOT:PSS underneath. This is translated into an ionic electric field, tangential to the interface that images the electric field applied to the PEDOT:PSS. We propose that this modification of the EDL, via application of the electrical field away from the cell culture medium, is at origin of the neural stem cell response to that field, when cultured on top of PEDOT:PSS. Despite the comparatively low value of the Debye length (estimated around 1 nm) with respect to the much larger cell to PEDOT:PSS surface distance, we believe that the perturbation of the EDL is the likely source of the increase of neuronal differentiation of the neural stem cells. We discuss other possible implications of that EDL modulation.

Electrospun piezoelectric scaffolds for cardiac tissue engineering.

The use of smart materials in tissue engineering is becoming increasingly appealing to provide additional functionalities and control over cell fate. The stages of tissue development and regeneration often require various electrical and electromechanical cues supported by the extracellular matrix, which is often neglected in most tissue engineering approaches. Particularly, in cardiac cells, electrical signals modulate cell activity and are responsible for the maintenance of the excitation-contraction coupling. Addition of electroconductive and topographical cues improves the biomimicry of cardiac tissues and plays an important role in driving cells towards the desired phenotype. Current platforms used to apply electrical stimulation to cells in vitro often require large external equipment and wires and electrodes immersed in the culture media, limiting the scalability and applicability of this process. Piezoelectric materials represent a shift in paradigm in materials and methods aimed at providing electrical stimulation to cardiac cells since they can produce and deliver electrical signals to cells and tissues by mechanoelectrical transduction. Despite the ability of piezoelectric materials to mimic the mechanoelectrical transduction of the heart, the use of these materials is limited in cardiac tissue engineering and methods to characterise piezoelectricity are often built in-house, which poses an additional difficulty when comparing results from the literature. In this work, we aim at providing an overview of the main challenges in cardiac tissue engineering and how piezoelectric materials could offer a solution to them. A revision on the existing literature in electrospun piezoelectric materials applied to cardiac tissue engineering is performed for the first time, as electrospinning plays an important role in the manufacturing of scaffolds with enhanced piezoelectricity and extracellular matrix native-like morphology. Finally, an overview of the current techniques used to evaluate piezoelectricity and their limitations is provided.

A Multimodal Stimulation Cell Culture Bioreactor for Tissue Engineering: A Numerical Modelling Approach.

The use of digital twins in tissue engineering (TE) applications is of paramount importance to reduce the number of in vitro and in vivo tests. To pursue this aim, a novel multimodal bioreactor is developed, combining 3D design with numerical stimulation. This approach will facilitate the reproducibility between studies and the platforms optimisation (physical and digital) to enhance TE. The new bioreactor was specifically designed to be additive manufactured, which could not be reproduced with conventional techniques. Specifically, the design suggested allows the application of dual stimulation (electrical and mechanical) of a scaffold cell culture. For the selection of the most appropriate material for bioreactor manufacturing several materials were assessed for their cytotoxicity. Numerical modelling methods were then applied to the new bioreactor using one of the most appropriate material (Polyethylene Terephthalate Glycol-modified (PETG)) to find the optimal stimulation input parameters for bone TE based on two reported in vitro studies.