Programmed biomolecule delivery to enable and direct cell migration for connective tissue repair

Abstract

Dense connective tissue injuries have limited repair, due to the paucity of cells at the wound site. We hypothesize that decreasing the density of the local extracellular matrix (ECM) in conjunction with releasing chemoattractive signals increases cellularity and tissue formation after injury. Using the knee meniscus as a model system, we query interstitial cell migration in the context of migratory barriers using a novel tissue Boyden chamber and show that a gradient of platelet-derived growth factor-AB (PDGF-AB) expedites migration through native tissue. To implement these signals in situ, we develop nanofibrous scaffolds with distinct fiber fractions that sequentially release active collagenase (to increase ECM porosity) and PDGF-AB (to attract endogenous cells) in a localized and coordinated manner. We show that, when placed into a meniscal defect, the controlled release of collagenase and PDGF-AB increases cellularity at the interface and within the scaffold, as well as integration with the surrounding tissue.

Influence of Fiber Stiffness on Meniscal Cell Migration into Dense Fibrous Networks

“…Specifically, nano‐ to micro‐scale polymer fibers can be generated by electrospinning and collected as either random or aligned fibrous networks to mimic the highly organized collagen fibers of these dense connective tissues. Recent advances in biomaterials design and electrospinning techniques have expanded the range of biophysical (e.g., alignment, diameter, and stiffness) and biochemical (e.g., adhesion ligand and growth factor) properties of scaffolds to better explore features that enable expedited tissue repair.…”

Transcriptomic analysis of bone and fibrous tissue morphogenesis during digit tip regeneration in the adult mouse

“…Modulating early scar formation by targeting fibrotic signaling pathways (Li et al, 2017) may also give stem/progenitor cells an opportunity to expand and differentiate. Finally, spatiotemporal delivery of morphogenic signaling molecules by genetically modified cells and/or biomaterials may help direct and sustain the regenerative process Taghiyar et al, 2017;Qu et al, 2017).…”

Hyaluronic Acid act as a Non - Invasive Marker for Diagnosis of Liver Fibrosis in the Patients of Chronic Hepatitis C

“…In current study, serum hyaluronic acid is extensively evaluated as a non-invasive marker among clinically diagnosed chronic hepatitis C patients. Hyaluronic acid (HA) is an anionic, non sulfated glycosaminogly can distributed widely throughout connective, epithelial, and neural tissues 12,13 . Both metabolic activities and serum concentration of HA are precisely regulated by hepatic sinusoids 14 .…”