Evaluating Thera-101 as a Low-Volume Resuscitation Fluid in a Model of Polytrauma.

Traumatic brain injury (TBI) and hemorrhage remain challenging to treat in austere conditions. Developing a therapeutic to mitigate the associated pathophysiology is critical to meet this treatment gap, especially as these injuries and associated high mortality are possibly preventable. Here, Thera-101 (T-101) was evaluated as low-volume resuscitative fluid in a rat model of TBI and hemorrhage. The therapeutic, T-101, is uniquely situated as a TBI and hemorrhage intervention. It contains a cocktail of proteins and microvesicles from the secretome of adipose-derived mesenchymal stromal cells that can act on repair and regenerative mechanisms associated with poly-trauma. T-101 efficacy was determined at 4, 24, 48, and 72 h post-injury by evaluating blood chemistry, inflammatory chemo/cytokines, histology, and diffusion tensor imaging. Blood chemistry indicated that T-101 reduced the markers of liver damage to Sham levels while the levels remained elevated with the control (saline) resuscitative fluid. Histology supports the potential protective effects of T-101 on the kidneys. Diffusion tensor imaging showed that the injury caused the most damage to the corpus callosum and the fimbria. Immunohistochemistry suggests that T-101 may mitigate astrocyte activation at 72 h. Together, these data suggest that T-101 may serve as a potential field deployable low-volume resuscitation therapeutic.

Comparative evaluation of mesenchymal stromal cell growth and osteogenic differentiation on a shape memory polymer scaffold.

Trauma-induced, critical-size bone defects pose a clinical challenge to heal. Albeit autografts are the standard-of-care, they are limited by their inability to be shaped to various defect geometries and often incur donor site complications. Herein, the combination of a "self-fitting" shape memory polymer (SMP) scaffold and seeded mesenchymal stromal cells (MSCs) was investigated as an alternative. The porous SMP scaffold, prepared from poly(ε-caprolactone) diacrylate (PCL-DA) and coated with polydopamine, provided conformal shaping and cell adhesion. MSCs from five tissues, amniotic (AMSCs), chorionic tissue (CHSCs), umbilical cord (UCSCs), adipose (ADSCs), and bone marrow (BMSCs) were evaluated for viability, density, and osteogenic differentiation on the SMP scaffold. BMSCs exhibited the fastest increase in cell density by day 3, but after day 10, CHSCs, UCSCs, and ADSCs approached similar cell density. BMSCs also showed the greatest calcification among the cell types, followed closely by ADSCs, CHSCs and AMSCs. Alkaline phosphatase (ALP) activity peaked at day 7 for AMSCs, UCSCs, ADSCs and BMSCs, and at day 14 for CHSCs, which had the greatest overall ALP activity. Of all the cell types, only scaffolds cultured with ADSCs in osteogenic media had increased hardness and local modulus as compared to blank scaffolds after 21 days of cell culture and osteogenic differentiation. Overall, ADSCs performed most favorably on the SMP scaffold. The SMP scaffold was able to support key cellular behaviors of MSCs and could potentially be a viable, regenerative alternative to autograft.