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.