Characterization of degradation kinetics of additively manufactured PLGA under variable mechanical loading paradigms.

Controlled degradation of biodegradable poly-lactic-co-glycolic acid (PLGA) trauma implants may increase interfragmentary loading which is known to accelerate fracture healing. Additive manufacturing allows us to tune the mechanical properties of PLGA scaffolds; however, little is known about this novel approach. The purpose of this study was to use in vitro and in vivo models to determine the degradative kinetics of additively manufactured test coupons fabricated with PLGA.

Developmental morphogens direct human induced pluripotent stem cells toward an annulus fibrosus-like cell phenotype.

Introduction: Therapeutic interventions for intervertebral disc herniation remain scarce due to the inability of endogenous annulus fibrosus (AF) cells to respond to injury and drive tissue regeneration. Unlike other orthopedic tissues, such as cartilage, delivery of exogenous cells to the site of annular injury remains underdeveloped, largely due to a lack of an ideal cell source and the invasive nature of cell isolation. Human induced pluripotent stem cells (iPSCs) can be differentiated to specific cell fates using biochemical factors and are, therefore, an invaluable tool for cell therapy approaches.

Tension-activated nanofiber patches delivering an anti-inflammatory drug improve repair in a goat intervertebral disc herniation model.

Conventional microdiscectomy treatment for intervertebral disc herniation alleviates pain but does not repair the annulus fibrosus, resulting in a high incidence of recurrent herniation and persistent dysfunction. The lack of repair and the acute inflammation that arise after injury can further compromise the disc and result in disc-wide degeneration in the long term. To address this clinical need, we developed tension-activated repair patches (TARPs) for annulus fibrosus repair and local delivery of the anti-inflammatory factor anakinra (a recombinant interleukin-1 receptor antagonist).

Gravity-based patterning of osteogenic factors to preserve bone structure after osteochondral injury in a large animal model.

Chondral and osteochondral repair strategies are limited by adverse bony changes that occur after injury. Bone resorption can cause entire scaffolds, engineered tissues, or even endogenous repair tissues to subside below the cartilage surface. To address this translational issue, we fabricated thick-shelled poly(D,L-lactide-co-glycolide) microcapsules containing the pro-osteogenic agents triiodothyronine and-glycerophosphate, and delivered these microcapsules in a large animal model of osteochondral injury to preserve bone structure.

Disrupted Surfaces of Porous Membranes Reduce Nuclear YAP Localization and Enhance Adipogenesis through Morphological Changes.

The disrupted surface of porous membranes, commonly used in tissue-chip and cellular coculture systems, is known to weaken cell-substrate interactions. Here, we investigated whether disrupted surfaces of membranes with micron and submicron scale pores affect yes-associated protein (YAP) localization and differentiation of adipose-derived stem cells. We found that these substrates reduce YAP nuclear localization through decreased cell spreading, consistent with reduced cell-substrate interactions, and in turn enhance adipogenesis while decreasing osteogenesis.

Stretch-responsive adhesive microcapsules for strain-regulated antibiotic release from fabric wound dressings.

Bacterial infection of a wound is a major complication that can significantly delay proper healing and even necessitate surgical debridement. Conventional non-woven fabric dressings, including gauzes, bandages and cotton wools, often fail in treating wound infections in a timely manner due to their passive release mechanism of antibiotics. Here, we propose adhesive mechanically-activated microcapsules (MAMCs) capable of strongly adhering to a fibrous matrix to achieve a self-regulated release of antibiotics upon uniaxial stretching of non-woven fabric dressings.

A challenging playing field: Identifying the endogenous impediments to annulus fibrosus repair.

Intervertebral disc (IVD) herniations, caused by annulus fibrosus (AF) tears that enable disc tissue extrusion beyond the disc space, are very prevalent, especially among adults in the third to fifth decade of life. Symptomatic herniations, in which the extruded tissue compresses surrounding nerves, are characterized by back pain, numbness, and tingling and can cause extreme physical disability. Patients whose symptoms persist after nonoperative intervention may undergo surgical removal of the herniated tissue via microdiscectomy surgery.

Mechano-activated biomolecule release in regenerating load-bearing tissue microenvironments.

Although mechanical loads are integral for musculoskeletal tissue homeostasis, overloading and traumatic events can result in tissue injury. Conventional drug delivery approaches for musculoskeletal tissue repair employ localized drug injections. However, rapid drug clearance and inadequate synchronization of molecule provision with healing progression render these methods ineffective.

Putting the Pieces in Place: Mobilizing Cellular Players to Improve Annulus Fibrosus Repair.

The intervertebral disc (IVD) is an integral load-bearing tissue that derives its function from its composite structure and extracellular matrix composition. IVD herniations involve the failure of the annulus fibrosus (AF) and the extrusion of the nucleus pulposus beyond the disc boundary. Disc herniations can impinge the neural elements and cause debilitating pain and loss of function, posing a significant burden on individual patients and society as a whole.

Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues.

Dense matrices impede interstitial cell migration and subsequent repair. We hypothesized that nuclear stiffness is a limiting factor in migration and posited that repair could be expedited by transiently decreasing nuclear stiffness. To test this, we interrogated the interstitial migratory capacity of adult meniscal cells through dense fibrous networks and adult tissue before and after nuclear softening via the application of a histone deacetylase inhibitor, Trichostatin A (TSA) or knockdown of the filamentous nuclear protein Lamin A/C.

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

Fibrous scaffolds fabricated via electrospinning are being explored to repair injuries within dense connective tissues. However, there is still much to be understood regarding the appropriate scaffold properties that best support tissue repair. In this study, the influence of the stiffness of electrospun fibers on cell invasion into fibrous scaffolds is investigated.

Mechanosensing at Cellular Interfaces.

At the plasma membrane interface, cells use various adhesions to sense their extracellular environment. These adhesions facilitate the transmission of mechanical signals that dictate cell behavior. This review discusses the mechanisms by which these mechanical signals are transduced through cell-matrix and cell-cell adhesions and how this mechanotransduction influences cell processes.

Membrane Pore Spacing Can Modulate Endothelial Cell-Substrate and Cell-Cell Interactions.

Mechanical cues and substrate interaction affect the manner in which cells adhere, spread, migrate and form tissues. With increased interest in tissue-on-a-chip and co-culture systems utilizing porous membranes, it is important to understand the role of disrupted surfaces on cellular behavior. Using a transparent glass membrane with defined pore geometries, we investigated endothelial fibronectin fibrillogenesis and formation of focal adhesions as well as development of intercellular junctions.

Effect of Simplified One-Step Drilling Protocol on Osseointegration.

This study was designed to compare the combined effect of two different drilling techniques (conventional expansion and one-step) and four different implant geometries in a beagle dog model. The nondecalcified bone-implant samples underwent histologic/metric analysis at 2 and 6 weeks. Morphologic analysis showed similarities between different drilling technique groups and implant geometries.