Amorphous silica fiber matrix biomaterials:An analysis of material synthesis and characterization for tissue engineering

Silica biomaterials including Bioglass offer great biocompatibility and bioactivity but fail to provide pore and degradation features needed for tissue engineering.Herein we report on the synthesis and characterization of novel amorphous silica fiber matrices to overcome these limitations.Amorphous silica fibers were fused by sintering to produce porous matrices.The effects of sacrificial polymer additives such as polyvinyl alcohol(PVA)and cellulose fibers(CF)on the sintering process were also studied.The resulting matrices formed between sintering temperatures of 1,350-1,550◦C retained their fiber structures.The matrices presented pores in the range of 50-200μm while higher sintering temperatures resulted in increased pore diameter.PVA addition to silica significantly reduced the pore diameter and porosity compared with silica matrices with or without the addition of CF.The PVA additive morphologically appeared to fuse the silica fibers to a greater extent and resulted in significantly higher compressive modulus and strength than the rest of the matrices synthesized.These matrices lost roughly 30%of their original mass in an in vitro degradation study over 40 weeks.All matrices absorbed 500 wt%of water and did not change in their overall morphology,size,or shape with hydration.These fiber matrices supported human mesenchymal stem cell adhesion,proliferation,and mineralized matrix production.Amorphous silica fiber biomaterials/matrices reported here are biodegradable and porous and closely resemble the native extracellular matrix structure and water absorption capacity.Extending the methodology reported here to alter matrix properties may lead to a variety of tissue engineering,implant,and drug delivery applications.

Nanofiber matrix formulations for the delivery of Exendin-4 for tendon regeneration: In vitro and in vivo assessment

Tendon and ligament injuries are the most common musculoskeletal injuries,which not only impact the quality of life but result in a massive economic burden.Surgical interventions for tendon/ligament injuries utilize biological and/or engineered grafts to reconstruct damaged tissue,but these have limitations.Engineered matrices confer superior physicochemical properties over biological grafts but lack desirable bioactivity to promote tissue healing.While incorporating drugs can enhance bioactivity,large matrix surface areas and hydrophobicity can lead to uncontrolled burst release and/or incomplete release due to binding.To overcome these limitations,we evaluated the delivery of a peptide growth factor(exendin-4;Ex-4)using an enhanced nanofiber matrix in a tendon injury model.To overcome drug surface binding due to matrix hydrophobicity of poly(caprolactone)(PCL)-which would be expected to enhance cell-material interactions-we blended PCL and cellulose acetate(CA)and electrospun nanofiber matrices with fiber diameters ranging from 600 to 1000 nm.To avoid burst release and protect the drug,we encapsulated Ex-4 in the open lumen of halloysite nanotubes(HNTs),sealed the HNT tube endings with a polymer blend,and mixed Ex-4-loaded HNTs into the polymer mixture before electrospinning.This reduced burst release from~75%to~40%,but did not alter matrix morphology,fiber diameter,or tensile properties.We evaluated the bioactivity of the Ex-4 nanofiber formulation by culturing human mesenchymal stem cells(hMSCs)on matrix surfaces for 21 days and measuring tenogenic differentiation,compared with nanofiber matrices in basal media alone.Strikingly,we observed that Ex-4 nanofiber matrices accelerated the hMSC proliferation rate and elevated levels of sulfated glycosaminoglycan,tendon-related genes(Scx,Mkx,and Tnmd),and ECM-related genes(Col-Ⅰ,Col-Ⅲ,and Dcn),compared to control.We then assessed the safety and efficacy of Ex-4 nanofiber matrices in a full-thickness rat Achilles tendon defect with histology,marker expression,functional walking track analysis,and mechanical testing.Our analysis confirmed that Ex-4 nanofiber matrices enhanced tendon healing and reduced fibrocartilage formation versus nanofiber matrices alone.These findings implicate Ex-4 as a potentially valuable tool for tendon tissue engineering.

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.