Biology subjects

Stegemann, J. P.

Publications and source records attributed to Stegemann, J. P..

2 recordsLinked to original sources

bioRxiv2024

Clickable PEG-norbornene microgels support suspension bioprinting and microvascular assembly

The development of perfusable and multiscale vascular networks remains one of the largest challenges in tissue engineering. As such, there is a need for the creation of customizable and facile methods to produce robustly vascularized constructs. In this study, secondarily crosslinkable (clickable) poly(ethylene glycol)-norbornene (PEGNB) microbeads were produced and evaluated for their ability to sequentially support suspension bioprinting and microvascular self-assembly towards the aim of engineering hierarchical vasculature. The clickable PEGNB microbead slurry exhibited mechanical behavior suitable for suspension bioprinting of sacrificial bioinks, could be UV crosslinked into a granular construct post-print, and withstood evacuation of the bioink and subsequent perfusion of the patterned void space. Endothelial and stromal cells co-embedded within jammed RGD-modified PEGNB microbead slurries assembled into capillary-scale vasculature after secondary crosslinking of the beads into granular constructs, with endothelial tubules forming within the interstitial space between microbeads and supported by the perivascular association of the stromal cells. Microvascular self-assembly was not impacted by printing sacrificial bioinks into the cell-laden microbead support bath before UV crosslinking. Collectively, these results demonstrate that clickable PEGNB microbeads are a versatile substrate for both suspension printing and microvascular culture and may be the foundation for a promising methodology to engineer hierarchical vasculature.

bioengineering↗

bioRxiv2019

Bioresponsive Microspheres for On-demand Delivery of Anti-inflammatory Cytokines for Osteoarthritis

Despite innovations in surgical interventions, treatment of cartilage injury in osteoarthritic joints remains a challenge due to concomitant inflammation. Obstructing a single dominant inflammatory cytokine have shown remarkable clinical benefits in rheumatoid arthritis, and similar strategies are being suggested to target inflammatory pathways in osteoarthritis (OA). Here we describe the utility of gelatin microspheres that are responsive to arthritic flares, resulting in on-demand, and spatiotemporally controlled release of anti-inflammatory cytokines for cartilage preservation and repair. These microspheres had net negative charge potential to sequester cationic anti-inflammatory cytokines, and the magnitude of the negative charge potential increased with increase in crosslinking density. The enzymatic degradation of the microcarriers was concentration dependent. Release of anti-inflammatory cytokines from the loaded microspheres was directly correlated with the degradation of the gelatin matrix. Exposure of the IL-4 and IL-13 loaded microspheres reduced the inflammation of chondrocytes up to 80%. Hence, the delivery of these microspheres in an osteoarthritic joint can attenuate the stimulation of chondrocytes to secrete catabolic factors including proteinases and nitric oxide. The microsphere format also allows for minimally invasive delivery and is less susceptible to mechanically-induced drug release and are conformant to the intra-articular space. Consequently, bioresponsive microspheres are an effective tool for OA prevention and treatment.

bioengineering↗