Bioactive polymeric materials and electrical stimulation strategies for musculoskeletal tissue repair and regeneration

Electrical stimulation(ES)is predominantly used as a physical therapy modality to promote tissue healing and functional recovery.Research efforts in both laboratory and clinical settings have shown the beneficial effects of this technique for the repair and regeneration of damaged tissues,which include muscle,bone,skin,nerve,tendons,and ligaments.The collective findings of these studies suggest ES enhances cell proliferation,extracellular matrix(ECM)production,secretion of several cytokines,and vasculature development leading to better tissue regeneration in multiple tissues.However,there is still a gap in the clinical relevance for ES to better repair tissue interfaces,as ES applied clinically is ineffective on deeper tissue.The use of a conducting material can transmit the stimulation applied from skin electrodes to the desired tissue and lead to an increased function on the repair of that tissue.Ionically conductive(IC)polymeric scaffolds in conjunction with ES may provide solutions to utilize this approach effectively.Injectable IC formulations and their scaffolds may provide solutions for applying ES into difficult to reach tissue types to enable tissue repair and regeneration.A better understanding of ES-mediated cell differentiation and associated molecular mechanisms including the immune response will allow standardization of procedures applicable for the next generation of regenerative medicine.ES,along with the use of IC scaffolds is more than sufficient for use as a treatment option for single tissue healing and may fulfill a role in interfacing multiple tissue types during the repair process.

Bioactive polymeric scaffolds for tissue engineering

A variety of engineered scaffolds have been created for tissue engineering using polymers,ceramics and their composites.Biomimicry has been adopted for majority of the three-dimensional(3D)scaffold design both in terms of physicochemical properties,as well as bioactivity for superior tissue regeneration.Scaffolds fabricated via salt leaching,particle sintering,hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo.Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity.Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution,not reproducible and involved multiple steps.The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery.This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores,bioactivity and degradation rate to enable tissue regeneration.Review highlights few examples of bioactive scaffold mediated nerve,muscle,tendon/ligament and bone regeneration.Regardless of the efforts required for optimization,a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.

Review: Bioengineering approach for the repair and regeneration of peripheral nerve

Complex craniofacial surgeries of damaged tissues have several limitations,which present complications and challenges when trying to replicate facial function and structure.Traditional treatment techniques have shown suitable nerve function regeneration with various drawbacks.As technology continues to advance,new methods have been explored in order to regenerate damaged nerves in an effort to more efficiently and effectively regain original function and structure.This article will summarize recent bioengineering strategies involving biodegradable composite scaffolds,bioactive factors,and external stimuli alone or in combination to support peripheral nerve regeneration.Particular emphasis is made on the contributions of growth factors and electrical stimulation on the regenerative process.

Biopolymer-nanotube nerve guidance conduit drug delivery for peripheral nerve regeneration:In vivo structural and functional assessment

Peripheral nerve injuries account for roughly 3%of all trauma patients with over 900,000 repair procedures annually in the US.Of all extremity peripheral nerve injuries,51%require nerve repair with a transected gap.The current gold-standard treatment for peripheral nerve injuries,autograft repair,has several shortcomings.Engineered constructs are currently only suitable for short gaps or small diameter nerves.Here,we investigate novel nerve guidance conduits with aligned microchannel porosity that deliver sustained-release of neurogenic 4-aminopyridine(4-AP)for peripheral nerve regeneration in a critical-size(15 mm)rat sciatic nerve transection model.The results of functional walking track analysis,morphometric evaluations of myelin development,and histological assessments of various markers confirmed the equivalency of our drug-conduit with autograft controls.Repaired nerves showed formation of thick myelin,presence of S100 and neurofilament markers,and promising functional recovery.The conduit’s aligned microchannel architecture may play a vital role in physically guiding axons for distal target reinnervation,while the sustained release of 4-AP may increase nerve conduction,and in turn synaptic neurotransmitter release and upregulation of critical Schwann cell neurotrophic factors.Overall,our nerve construct design facilitates efficient and efficacious peripheral nerve regeneration via a drug delivery system that is feasible for clinical applications.