Long Range Forces from Two Neutrino Exchange Revisited

The exchange of two massless neutrinos gives rise to a long range force which couples to weakly charged matter. As has been noted previously in the literature, the potential for this force is \VN \propto G_{F}^2 / r^5 with monopole-monople, spin-spin and more complicated interactions. Unfortunately, this is far too small to be observed in present day experiments. We calculate \VN explicitly in the electroweak theory, and show that under very general assumptions forces arising from the exchange of two massless fermions can at best yield $1 / r^5$ potentials.Comment: 5 pages + 1 figure (not included), UFIFT-HEP-92-28/HUTP-92-A04

Characterization of a unique technique for culturing primary adult human epithelial progenitor/“stem cells”

Abstract Background Primary keratinocytes derived from epidermis, oral mucosa, and urothelium are used in construction of cell based wound healing devices and in regenerative medicine. This study presents in vitro technology that rapidly expands keratinocytes in culture by growing monolayers under large volumes of serum-free, essential fatty acid free, low calcium medium that is replaced every 24 hrs. Methods Primary cell cultures were produced from epidermal skin, oral mucosa and ureter by trypsinization of tissue. Cells were grown using Epilife medium with growth factors under high medium volumes. Once densely confluent, the keratinocyte monolayer produced cells in suspension in the overlying medium that can be harvested every 24 hrs. over a 7–10 day period. The cell suspension (approximately 8 X 105 cells/ml) is poured into a new flask to form another confluent monolayer over 2–4 days. This new culture, in turn produced additional cell suspensions that when serially passed expand the cell strain over 2–3 months, without the use of enzymes to split the cultures. The cell suspension, called epithelial Pop Up Keratinocytes (ePUKs) were analyzed for culture expansion, cell size and glucose utilization, attachment to carrier beads, micro-spheroid formation, induction of keratinocyte differentiation, and characterized by immunohistochemistry. Results The ePUKs expanded greatly in culture, attached to carrier beads, did not form micro-spheroids, used approximately 50% of medium glucose over 24 hrs., contained a greater portion of smaller diameter cells (8–10 microns), reverted to classical appearing cultures when returned to routine feeding schedules (48 hrs. and 15 ml/T-75 flask) and can be differentiated by either adding 1.2 mM medium calcium, or essential fatty acids. The ePUK cells are identified as cycling (Ki67 expressing) basal cells (p63, K14 expressing). Conclusions Using this primary culture technique, large quantities of epithelial cells can be generated without the use of the enzyme trypsin to split the cultures. The cells are small in diameter and have basal cell progenitor/”stem” (P/SC) cell characteristics induced by daily feeding with larger than normal medium volumes. The ePUK epithelial cells have the potential to be used in regenerative medicine and for basic studies of epithelia P/SC phenotype.http://deepblue.lib.umich.edu/bitstream/2027.42/112344/1/12895_2011_Article_127.pd

Evaluation of Transplanted Tissue-Engineered Oral Mucosa Equivalents in Severe Combined Immunodeficient Mice

The aim of this study was to determine the optimal stage of development at which transplant human ex vivo-produced oral mucosa equivalents (EVPOMEs) in vivo. EVPOMEs were generated in a serum-free culture system, without the use of an irradiated xenogeneic feeder layer, by seeding human oral keratinocytes onto a human cadaveric dermal equivalent, AlloDerm. EVPOMEs were cultured for 4 days submerged and then for 7 or 14 days at an air-liquid interface to initiate stratification before transplantation into SCID mice. AlloDerm, without epithelium, was used as a control. Mice were killed on days 3, 10, and 21 posttransplantation. Epithelium of the transplanted EVPOMEs was evaluated with the differentiation marker keratin 10/13. Dermal microvessel ingrowth was determined by immunohistochemistry with a mouse vascular marker, lectin binding from Triticum vulgaris. The presence and stratification of the epithelium were correlated with revascularization of the underlying dermis. The microvessel density of AlloDerm without epithelium was less than that of EVPOMEs with an epithelial layer. Microvessel density of the dermis varied directly with the degree of epithelial stratification of the EVPOMEs. The EVPOMEs cultured at an air-liquid interface for 7 days had the optimal balance of neoangiogenesis and epithelial differentiation necessary for in vivo grafting.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63269/1/107632703762687645.pd

Fabrication of Large Size Ex Vivo-Produced Oral Mucosal Equivalents for Clinical Application

The soft tissue reconstruction of significant avulsed and/or surgically created tissue defects requires the ability to manufacture substantial soft tissue constructs for repair of the resulting wounds. In this study, we detail the issues that need to be addressed in upsizing the manufacture of larger tissue-engineered devices (ex vivo-produced oral mucosa equivalent [EVPOME]) in vitro from a methodology previously used for smaller constructs. The larger-sized EVPOME, consisting of autologous human oral keratinocytes and a dermal substitute, AlloDerm?, was fabricated for the purpose of reconstructing large clinical defects. Regulated as an autologous somatic cell therapy product, the fabrication process abided by current Good Manufacturing Practices and current Good Tissue Practices as required by the Center for Biologics Evaluation and Research (CBER) of the United States Food and Drug Administration (FDA). Successful fabrication of large EVPOMEs utilized a higher cell seeding density (5.3?105 cells/cm2) with a relatively thinner AlloDerm, ranging from 356.6 to 508.0??m in thickness. During the air?liquid interface culture, the thickness of the scaffold affected the medium diffusion rate, which, in turn, resulted in changes of epithelial stratification. Histologically, keratinocyte progenitor (p63), proliferation (Ki-67), and late differentiation marker (filaggrin) expression showed differences correlating with the expression of glucose transporter-1 (GLUT1) in the EVPOMEs from the thickest (550?1020??m) to the thinnest (228.6?330.2??m) AlloDerm scaffold. Glucose consumption and 2-deoxyglucose (2DG) uptake showed direct correlation with scaffold thickness. The scaffold size and thickness have an impact on the cellular phenotype and epithelial maturation in the manufacturing process of the EVPOME due to the glucose accessibility influenced by the diffusion rate. These outcomes provide basic strategies to manufacture a large-sized, healthy EVPOME graft for reconstructing large mucosa defects.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140251/1/ten.tec.2014.0600.pd

Analyzing Data from Multivariate Directed Graphs: An Application to Social Networks

1 online resource (PDF, 29 pages

Extracellular matrixâ based scaffolding technologies for periodontal and periâ implant soft tissue regeneration

The present article focuses on the properties and indications of scaffoldâ based extracellular matrix (ECM) technologies as alternatives to autogenous soft tissue grafts for periodontal and periâ implant plastic surgical reconstruction. The different processing methods for the creation of cellâ free constructs resulting in preservation of the extracellular matrices influence the characteristics and behavior of scaffolding biomaterials. The aim of this review is to discuss the properties, clinical application, and limitations of ECMâ based scaffold technologies in periodontal and periâ implant soft tissue augmentation when used as alternatives to autogenous soft tissue grafts.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153617/1/jper10427.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153617/2/jper10427_am.pd

Characterizing Morphology and Nonlinear Elastic Properties of Normal and Thermally Stressed Engineered Oral Mucosal Tissues Using Scanning Acoustic Microscopy

This study examines the use of high-resolution ultrasound to monitor changes in the morphology and nonlinear elastic properties of engineered oral mucosal tissues under normal and thermally stressed culture conditions. Nonlinear elastic properties were determined by first developing strain maps from acoustic ultrasound, followed by fitting of nonlinear stress?strain data to a 1-term Ogden model. Testing examined a clinically developed ex vivo produced oral mucosa equivalent (EVPOME). As seeded cells proliferate on an EVPOME surface, they produce a keratinized protective upper layer that fills in and smoothens out surface irregularities. These transformations can also alter the nonlinear stress/strain parameters as EVPOME cells differentiate. This EVPOME behavior is similar to those of natural oral mucosal tissues and in contrast to an unseeded scaffold. If ultrasonic monitoring could be developed, then tissue cultivation could be adjusted in-process to account for biological variations in their development of the stratified cellular layer. In addition to ultrasonic testing, an in-house-built compression system capable of accurate measurements on small (?1.0?1.5?cm2) tissue samples is presented. Results showed a near 2.5-fold difference in the stiffness properties between the unstressed EVPOME and the noncell-seeded acellular scaffold (AlloDerm?). There were also 4?greater differences in root mean square values of the thickness in the unseeded AlloDerm compared to the mature unstressed EVPOME; this is a strong indicator for quantifying surface roughness.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140241/1/ten.tec.2012.0467.pd

Biologicsâ based regenerative technologies for periodontal soft tissue engineering

This manuscript provides a stateâ ofâ theâ art review on the efficacy of biologics in root coverage procedures, including enamel matrix derivative, plateletâ derived growth factor, platelet concentrates, and fibroblastâ growth factorâ 2. The mechanism of action and the rationale for using biologics in periodontal plastic surgery, as well as their anticipated benefits when compared with conventional approaches are discussed. Although the clinical significance is still under investigation, preclinical data and histologic evidence demonstrate that biologicâ based techniques are able to promote periodontal regeneration coupled with the provision of tooth root coverage.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154295/1/jper10426_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154295/2/jper10426.pd

Comparison of two decellularized dermal equivalents

Immunologically inert allogeneic acellular dermal scaffolds provide a matrix with molecular architecture close to native tissues, which synthetic scaffolds cannot. Not all nature‐derived scaffolds possess the same biological and physical properties. The different properties of scaffolds supporting cellular growth used for manufacturing tissue engineered grafts could lead to different implantation results. The scaffold properties should be carefully considered in order to meet the expected outcomes of tissue engineered grafts. In this report, we evaluated the cellular growth on AlloDerm® and Allopatch, 2 acellular scaffolds derived from human cadaver skin, using a fabricated 3D organotypic culture with primary human oral keratinocytes to produce an ex vivo produced oral mucosa equivalent (EVPOME). A well stratified epithelium could be constructed on both scaffolds. AlloDerm® and Allopatch EVPOMEs were also implanted into severe combined immunodeficiency mice to compare the ingrowth of blood vessels into the dermal component of the two EVPOMEs. Blood vessel counts were 3.3 times higher (p = .01) within Allopatch EVPOMEs than within AlloDerm® EVPOMEs. An oral and skin keratinocyte co‐culture, separated by a physical barrier to create a cell‐free zone, was used to evaluate cell migration on AlloDerm® and Allopatch. Slower cell migration was observed on Allopatch than on AlloDerm®.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143690/1/term2530.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143690/2/term2530_am.pd

Autogenous soft tissue grafting for periodontal and periâ implant plastic surgical reconstruction

This stateâ ofâ theâ art review presents the latest evidence and the current status of autogenous soft tissue grafting for soft tissue augmentation and recession coverage at teeth and dental implant sites. The indications and predictability of the free gingival graft and connective tissue graft (CTG) techniques are highlighted, together with their expected clinical and esthetic outcomes. CTGs can be harvested from the maxillary tuberosity or from palate with different approaches that can have an impact on graft quality and patient morbidity. The influence of CTGs on soft tissue thickness and keratinized tissue width are also discussed.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153773/1/jper10428_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153773/2/jper10428.pd