Peristalsis is a nuanced mechanical stimulus comprised of multi-axial strain (radial and axial strain) and shear stress. Forces associated with peristalsis regulate diverse biological functions including digestion, reproductive function, and urine dynamics. Given the central role peristalsis plays in physiology and pathophysiology, we were motivated to design a bioreactor capable of holistically mimicking peristalsis. We engineered a novel rotating screw-drive based design combined with a peristaltic pump, in order to deliver multiaxial strain and concurrent shear stress to a biocompatible polydimethylsiloxane (PDMS) membrane “wall”. Radial indentation and rotation of the screw drive against the wall demonstrated multi-axial strain evaluated via finite element modeling. Experimental measurements of strain using piezoelectric strain resistors were in close alignment of model-predicted values (15.9 ± 4.2% vs. 15.2% predicted). Modeling of shear stress on the ‘wall’ indicated a uniform velocity profile and a moderate shear stress of 0.4 Pa. Human mesenchymal stem cells (hMSCs) seeded on the PDMS ‘wall’ and stimulated with peristalsis demonstrated dramatic changes in actin filament alignment, proliferation, and nuclear morphology compared to static controls, perfusion or strain, indicating that hMSCs sensed and responded to peristalsis uniquely. Lastly, significant differences were observed in gene expression patterns of Calponin, Caldesmon, Smooth Muscle Actin, and Transgelin, corroborating the propensity of hMSCs toward myogenic differentiation in response to peristalsis. Collectively, our data suggests that the peristalsis bioreactor is capable of generating concurrent multi-axial strain and shear stress on a ‘wall’. hMSCs experience peristalsis differently than perfusion or strain, resulting in changes in proliferation, actin fiber organization, smooth muscle actin expression, and genetic markers of differentiation. The peristalsis bioreactor device has broad utility in the study of development and disease in several organ systems.

Growth factors (GF) are critical cytokines in wound healing. However, the direct delivery of these biochemical cues into a wound site significantly increases the cost of wound dressings and can lead to a strong immunological response due to the introduction of a foreign source of GFs. To overcome this challenge, we designed a poly(ethylene glycol) diacrylate (PEGDA) hydrogel with the potential capacity to sequester autologous GFs directly from the wound site. We demonstrated that synthetic peptide sequences covalently tethered to PEGDA hydrogels physically retained human transforming growth factor beta 1 (hTGFβ1) and human vascular endothelial growth factor (hVEGF) at 3.2 and 0.6 ng/mm2, respectively. In addition, we demonstrated that retained hTGFβ1 and hVEGF enhanced human dermal fibroblasts (HDFa) average cell surface area and proliferation, respectively, and that exposure to both GFs resulted in up to 1.9-fold higher fraction of area covered relative to the control. After five days in culture, relative to the control surface, non-covalently bound hTGFβ1 significantly increased the expression of collagen type I and hTGFβ1 and downregulated vimentin and matrix metalloproteinase 1 expression. Cumulatively, the response of HDFa to hTGFβ1 aligns well with the expected response of fibroblasts during the early stages of wound healing.

Gulf War Illness (GWI) results from chemical exposure during the Gulf War, with notable impacts on gastrointestinal motility. Due to the limited demographic impacted by this ailment, an in‐depth investigation of the GWI has yielded little regarding the underlying pathophysiological mechanisms. Here, the hypothesis that exposure to pyridostigmine bromide (PB) results in severe enteric neuro‐inflammation, that cascades to disruptions in colonic motility, is tested. The analyses are performed on male C57BL/6 mice that are treated with physiologically similar doses of PB given to GW veterans. When colonic motility is assessed, GWI colons have significantly reduced forces in response to acetylcholine or electrical field stimulation. GWI is also accompanied by high levels of pro‐inflammatory cytokines and chemokines, associated with increased numbers of CD40+ pro‐inflammatory macrophages within the myenteric plexus. Enteric neurons responsible for mediating colonic motility reside within the myenteric plexus, and PB exposure reduced their numbers. Significant smooth muscle hypertrophy is also observed due to increased inflammation. Together, the results show that PB exposure caused functional and anatomical dysfunction, promoting impaired motility within the colon. Achieving a greater understanding of the mechanisms of GWI will allow more refinement in therapeutic options that improve veterans’ quality of life.

The tumor microenvironment encompasses complex interactions between diverse cell types including those of the immune system. Tumor–immune interactions occur in all phases of cancer, where the immune system can either eliminate or reach an equilibrium with cancer. These processes eventually lead to overt malignant growth because of active tumor-based immune suppression. The design of efficient immunotherapies depends on deepening our understanding of these complex immune mechanisms. Not only do advanced biomaterials and tissue engineering strategies re-engineer tumor immune microenvironments, they also provide valuable test-beds to refine the development of novel therapeutics. This chapter highlights nuances and challenges posed when engineering the tumor immune microenvironment, and the goals of various types of immunotherapy. In this context, the chapter examines advances in 3D biomaterials and tissue engineering strategies used to expand our understanding of tumor–immune interactions, and how engineered platforms are being applied toward immunotherapy development.