Nonlinear optical molecular imaging and quantitative analytic methods were developed to non-invasively assess the viability of tissue-engineered constructs manufactured from primary human cells. Label-free optical measures of local tissue structure and biochemistry characterized morphologic and functional differences between controls and stressed constructs. Rigorous statistical analysis accounted for variability between human patients. Fluorescence intensity-based spatial assessment and metabolic sensing differentiated controls from thermally-stressed and from metabolically-stressed constructs. Fluorescence lifetime-based sensing differentiated controls from thermally-stressed constructs. Unlike traditional histological (found to be generally reliable, but destructive) and biochemical (non-invasive, but found to be unreliable) tissue analyses, label-free optical assessments had the advantages of being both non-invasive and reliable. Thus, such optical measures could serve as reliable manufacturing release criteria for cell-based tissue-engineered constructs prior to human implantation, thereby addressing a critical regulatory need in regenerative medicine.
A photon-tissue interaction (PTI) model was developed and employed to analyze 96 pairs of reflectance and fluorescence spectra from freshly excised human pancreatic tissues. For each pair of spectra, the PTI model extracted a cellular nuclear size parameter from the measured reflectance, and the relative contributions of extracellular and intracellular fluorophores to the intrinsic fluorescence. The results suggest that reflectance and fluorescence spectroscopies have the potential to quantitatively distinguish among pancreatic tissue types, including normal pancreatic tissue, pancreatitis, and pancreatic adenocarcinoma.
Bone composition and biomechanics at the tissue-level are important
contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate
anabolic therapy for the treatment of osteoporosis that increases bone
formation, bone mass, and bone strength in animal studies, but its effect on
bone quality at the tissue-level has received little attention. Pre-clinical
studies of Scl-Ab have recently expanded to include diseases with altered
collagen and material properties such as Osteogenesis Imperfecta (OI). The
purpose of this study was to investigate the role of Scl-Ab on bone quality by
determining bone material composition and tissue-level mechanical properties in
normal wild type (WT) tissue, as well as mice with a typical OI Gly→Cys
mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult
(6-month-old) WT and Brtl/+ mice were treated for 5 weeks with Scl-Ab.
Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy)
and biomechanical testing (nanoindentation) were performed at multiple tissue
ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages
of 2–4wks. However, no treatment related changes were observed in
mineral to matrix levels at mid-cortex, and elastic modulus was not altered by
Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically
observed in adult Brtl/+ OI mice (at tissue ages >3wk) and rapidly
growing Brtl/+ (at tissue ages > 4wk) mice compared to WT. At identical
tissue ages defined by fluorescent labels adult mice had generally lower mineral
to matrix ratios and a greater elastic modulus than rapidly growing mice,
demonstrating that bone matrix quality can be influenced by animal age and
tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix
chemistry of newly formed bone while not affecting the elastic modulus, induces
similar changes between Brtl/+ and WT mice, and provides new insight into the
interaction between tissue age and animal age on bone quality.
Eighty-six lamb s were randomly allotted to treatment (heavy vs light slaughter weight ) within breed (Targhee vs Suffolk x Ta rghee) and sex (rams vs wethers) .Lamb s in the lightwe ight group were fed to an ave rage weight of approximately 109 lb . and the heavyweight group was fed to an average we ight of approximately 136 pounds .
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