Purpose: Surgical reconstruction of intra-articular ligament injuries is hampered by the poor regenerative potential of the tissue. We hypothesized that a novel composite polymer ''neoligament'' seeded with progenitor cells and growth factors would be effective in regenerating native ligamentous tissue. Methods: We synthesized a fumarate-derivative of polycaprolactone fumarate (PCLF) to create macro-porous scaffolds to allow cell-cell communication and nutrient flow. Clinical grade human adipose tissue-derived human mesenchymal stem cells (AMSCs) were cultured in 5% human platelet lysate (PL) and seeded on scaffolds using a dynamic bioreactor. Cell growth, viability, and differentiation were examined using metabolic assays and immunostaining for ligament-related markers (e.g., glycosaminoglycans [GAGs], alkaline phosphatase [ALP], collagens, and tenascin-C). Results: AMSCs seeded on three-dimensional (3D) PCLF scaffolds remain viable for at least 2 weeks with proliferating cells filling the pores. AMSC proliferation rates increased in PL compared to fetal bovine serum (FBS) ( p < 0.05). Cells had a low baseline expression of ALP and GAG, but increased expression of total collagen when induced by the ligament and tenogenic growth factor fibroblast growth factor 2 (FGF-2), especially when cultured in the presence of PL ( p < 0.01) instead of FBS ( p < 0.05). FGF-2 and PL also significantly increased immunostaining of tenascin-C and collagen at 2 and 4 weeks compared with human fibroblasts. Summary: Our results demonstrate that AMSCs proliferate and eventually produce a collagen-rich extracellular matrix on porous PCLF scaffolds. This novel scaffold has potential in stem cell engineering and ligament regeneration.

Introduction The purpose of this study was to determine 1) if stable heart-failure patients with reduced ejection fraction (HFrEF) have elevated extravascular lung water (EVLW) versus healthy control subjects, and 2) the effect of acute β2AR agonist inhalation on lung fluid balance. Methods Twenty-two stable HFrEF patients and 18 age- and sex-matched healthy subjects were studied. Lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary conductance (DmCO), pulmonary capillary blood volume (Vc) (via rebreathe) and lung tissue volume (Vtis) (via computed tomography) were assessed before and within 30 min of administration of nebulized albuterol. EVLW was derived as Vtis – Vc. Results Pre-albuterol, Vtis and EVLW were greater in HFrEF vs. control (998 ± 200 vs. 884 ± 123 ml, P = 0.041; 943 ± 202 vs. 802 ± 133 ml, P = 0.015, respectively). Albuterol decreased Vtis and EVLW in HFrEF (−4.6 ± 7.8%, P = 0.010; −4.6 ± 8.8%, P = 0.018) and control (−2.8 ± 4.9%, P = 0.029; −3.0 ± 5.7%, P = 0.045). There was an inverse relationship between pre-albuterol values and the pre- to post-albuterol change for EVLW (r2 = −0.264, P = 0.015) and DmCO (r2 = −0.343, P = 0.004) in HFrEF only. Conclusion Lung fluid is elevated in stable HFrEF patients relative to healthy subjects. Stimulation of the β2ARs may cause fluid removal in HFrEF, especially in patients who exhibit greater evidence for increased lung water at baseline.

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In humans, a novel allosteric hemoglobin-oxygen affinity modulator was administered to comprehensively examine the cardiopulmonary consequences of stabilizing a portion of the available hemoglobin in a high-oxygen affinity state during submaximal exercise in normoxia and hypoxia. Oral administration of voxelotor enhanced arterial oxygen saturation during submaximal exercise without altering oxygen consumption and central hemodynamics; however, the partial pressure of arterial carbon dioxide was reduced and the partial pressure of arterial oxygen was increased implying that hyperventilation also contributed to the increase in oxygen saturation. The preservation of arterial oxygen saturation and content was particularly evident during hypoxic submaximal exercise, when arterial desaturation typically occurs, but this did not influence arterial-venous oxygen difference.

Introduction Pulmonary congestion is a common finding of heart failure (HF), but it remains unclear how pulmonary and heart blood volumes (Vp and Vh) and extravascular lung water (EVLW) change in stable HF and impact lung function. Methods Fourteen patients with HF (age: 68±11 y; LVEF: 33±8%) and 12 controls (age: 65±9 y) were recruited. A pulmonary function test, thoracic CT scan, and contrast perfusion scan were performed. From the thoracic scan, a histogram of CT attenuation of lung tissue was generated and skew, kurtosis, and full-width half-max were calculated as surrogates of EVLW. Blood volumes were calculated from the transit time of the contrast through the great vessels of the heart. Results Patients with HF had greater Vp and Vh (Vp: 0.55±0.21 l v.s 0.41±0.13 l; Vh: 0.53±0.33 l vs. 0.40±0.15 l) and EVLW (skew: 3.2±0.5 vs. 3.7±0.7; kurtosis: 19.4±6.6 vs. 25.9±9.4; FWHM: 73±13 vs 59±9Hu). Spirometric measures were decreased in HF (%-predicted FVC: 86±17% vs. 104±9%; FEV1: 83±20% vs. 105±11%; FEF25–75: 82±42% vs. 115±43%). Vp was associated with decreased expiratory flows, while EVLW was associated with decreased lung volumes. Conclusions Congestion in stable patients with HF includes expanded Vp and increased EVLW associated with reductions in lung volumes and expiratory flows.