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.

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.

Additive manufacturing of biodegradable porous orthopaedic screw

Advent of additive manufacturing in biomedical field has nurtured fabrication of complex,customizable and reproducible orthopaedic implants.Layer-by-layer deposition of biodegradable polymer employed in development of porous orthopaedic screws promises gradual dissolution and complete metabolic resorption thereby overcoming the limitations of conventional metallic screws.In the present study,screws with different pore sizes(916×918μm to 254×146μm)were 3D printed at 200μm layer height by varying printing parameters such as print speed,fill density and travel speed to augment the bone ingrowth.Micro-CT analysis and scanning electron micrographs of screws with 45%fill density confirmed porous interconnections(40.1%)and optimal pore size(259×207×200μm)without compromising the mechanical strength(24.58±1.36 MPa).Due to the open pore structure,the 3D printed screws showed increased weight gain due to the deposition of calcium when incubated in simulated body fluid.Osteoblast-like cells attached on screw and infiltrated into the pores over 14 days of in vitro culture.Further,the screws also supported greater human mesenchymal stem cell adhesion,proliferation and mineralized matrix synthesis over a period of 21 days in vitro culture as compared to non-porous screws.These porous screws showed significantly increased vascularization in a rat subcutaneous implantation as compared to control screws.Porous screws produced by additive manufacturing may promote better osteointegration due to enhanced mineralization and vascularization.