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Surface-Modified Piezoelectric Copolymer Poly(vinylidene fluoride–trifluoroethylene) Supporting Physiological Extracellular Matrixes to Enhance Mesenchymal Stem Cell Adhesion for Nanoscale Mechanical Stimulation

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Hannah Donnelly, Mark Robert Sprott, Anup Poudel, Paul Campsie, Peter Childs, S. Reid, Manuel Salmerón‐Sánchez, Manus Biggs, Matthew J. Dalby

A future bone graft might not need only the right cells. It may also need the right surface—and tiny vibrations that help those cells begin turning into bone.

Abstract

There is an unmet clinical need to provide viable bone grafts for clinical use. Autologous bone, one of the most commonly transplanted tissues, is often used but is associated with donor site morbidity. Tissue engineering strategies to differentiate an autologous cell source, such as mesenchymal stromal cells (MSCs), into a potential bone-graft material could help to fulfill clinical demand. However, osteogenesis of MSCs can typically require long culture periods that are impractical in a clinical setting and can lead to significant cost. Investigation into strategies that optimize cell production is essential. Here, we use the piezoelectric copolymer poly(vinylidene fluoride−trifluoroethylene) (PVDFTrFE), functionalized with a poly(ethyl acrylate) (PEA) coating Supporting Information that drives fibronectin network formation, to enhance MSC adhesion and to present growth factors in the solid phase. Dynamic electrical cues are then incorporated, via a nanovibrational bioreactor, and the MSC response to electromechanical stimulation is investigated.

Transcript

A future bone graft might not need only the right cells. It may also need the right surface—and tiny vibrations that help those cells begin turning into bone. Bone repair remains difficult in the clinic. The usual graft comes from the patient’s own body, but its supply is limited and harvesting it requires another operation that can cause harm at the donor site.

Other grafts can be limited by the quality of the donor tissue or by the risk that the patient’s immune system reacts to it. These problems have encouraged the development of materials designed to help the body regenerate bone. The central idea is like giving a climber both a handhold and a gentle rhythm to move against.

The material is coated to help cells grip it, while mechanical stimulation supplies another cue found in bone. The material can produce body-relevant electrical signals when it is mechanically stimulated. The goal is to combine several signals associated with bone and help the cells become bone-forming cells.

The material produced a voltage when it was vibrated. Electrically prepared films produced a stronger voltage than films that were not electrically prepared. That difference matters because the vibration is not only movement. In the electrically prepared material, movement can also create an electrical cue for the cells.

Without pPEA and FN, the films did not facilitate long-term cellular culture, whereas conditions with both pPEA and FN were able to support it. Together, the coating and the network made cells spread out more, become less round, and form longer attachment structures, regardless of the electrical preparation.

Early attachment matters because it can determine whether cells remain healthy and respond to later treatment. Here, the added surface coating made cells spread out more, become less round, and form longer attachment structures, regardless of the film’s electrical orientation.

Here is the catch: the electrically prepared material responds to mechanical stimulation, but the uncoated material does not support the cell–material interaction needed to use that response. Adding the coating and the attachment network allowed the system to use low-amplitude, high-frequency mechanical stimulation.

In other words, the surface made the electrically active material biologically usable. The strongest result appeared when the coated, electrically prepared films carrying a bone-related growth signal were also given nanoscale mechanical stimulation.

Both early indicators of bone formation increased only under that combined condition. The increase compared with unstimulated films suggests that nanoscale motion may strengthen the cells’ early commitment toward becoming bone-forming cells.

The existing cell-growing system can promote bone formation, but its long culture time limits clinical use. This study found that the electrically active material improved cell attachment and early bone-forming commitment, while the coating improved cell survival and adhesion.

The bioreactor has potential clinical applications, but its culture time of more than twenty-eight days currently hinders translation into clinical use. Further investigating the system may help optimize production of useful bone-forming cells, while the coatings improve cell viability and adhesion.

Future work will further investigate the inclusion of BMP-2 in the PVDF-TrFE system and continue exploring the system’s osteogenic potential. The study suggests that combining a cell-friendly coating with electrically active material and nanoscale motion can improve early bone-forming behavior.

That could help make engineered bone grafts more practical, though more work is needed.

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