Multicellular bioprinted skin facilitates human-like skin architecture in vivo.

Bioprinting is a promising alternative method to generate skin substitutes because it can replicate the structural organization of the skin into biomimetic layers in vitro. In this study, six primary human skin cell types were used to bioprint a trilayer skin construct consisting of epidermis, dermis, and hypodermis. Transplantation of the bioprinted skin with human cells onto full-thickness wounds of nu/nu mice promoted rapid vascularization and formation of epidermal rete ridges analogous to the native human epidermis, with a normal-looking extracellular matrix.

Bioprinting small diameter blood vessel constructs with an endothelial and smooth muscle cell bilayer in a single step.

Bioengineered artificial blood vessels have been a major area of interest over the last decade. Of particular interest are small diameter vessels, as surgical options are currently limited. This study aimed to fabricate a small diameter, heterogeneous bilayer blood vessel-like construct in a single step with gelatin methacryloyl (GelMA) bioink using a 3D micro-extrusion bioprinter on a solid platform.

Bioprinted Skin Recapitulates Normal Collagen Remodeling in Full-Thickness Wounds.

Over 1 million burn injuries are treated annually in the United States, and current tissue engineered skin fails to meet the need for full-thickness replacement. Bioprinting technology has allowed fabrication of full-thickness skin and has demonstrated the ability to close full-thickness wounds. However, analysis of collagen remodeling in wounds treated with bioprinted skin has not been reported.

ECM concentration and cell-mediated traction forces play a role in vascular network assembly in 3D bioprinted tissue.

Tissue vascularization is critical to enable oxygen and nutrient supply. Therefore, establishing expedient vasculature is necessary for the survival of tissue after transplantation. The use of biomechanical forces, such as cell-induced traction forces, may be a promising method to encourage growth of the vascular network.

Skin bioprinting: the future of burn wound reconstruction?

Burns are a significant cause of trauma, and over the years, the focus of patient care has shifted from just survival to facilitation of improved functional outcomes. Typically, burn treatment, especially in the case of extensive burn injuries, involves surgical excision of injured skin and reconstruction of the burn injury with the aid of skin substitutes. Conventional skin substitutes do not contain all skin cell types and do not facilitate recapitulation of native skin physiology.

Chronic Splenic Abscess as the First Manifestation of Pancreatic Tail Tumor.

Pancreatic carcinoma is still associated with a poor survival due to the late presentation. Excluding head of pancreas tumor, manifestations are often vague resulting in delayed diagnosis. Manifestations as infective complications are rare, and in topic countries where infection remains common, diagnosis will be further delayed.

Advances in Skin Substitutes-Potential of Tissue Engineered Skin for Facilitating Anti-Fibrotic Healing.

Skin protects the body from exogenous substances and functions as a barrier to fluid loss and trauma. The skin comprises of epidermal, dermal and hypodermal layers, which mainly contain keratinocytes, fibroblasts and adipocytes, respectively, typically embedded on extracellular matrix made up of glycosaminoglycans and fibrous proteins. When the integrity of skin is compromised due to injury as in burns the coverage of skin has to be restored to facilitate repair and regeneration.

The effect of keratinocytes on the biomechanical characteristics and pore microstructure of tissue engineered skin using deep dermal fibroblasts.

Fibrosis affects most organs, it results in replacement of normal parenchymal tissue with collagen-rich extracellular matrix, which compromises tissue architecture and ultimately causes loss of function of the affected organ. Biochemical pathways that contribute to fibrosis have been extensively studied, but the role of biomechanical signaling in fibrosis is not clearly understood. In this study, we assessed the effect keratinocytes have on the biomechanical characteristics and pore microstructure of tissue engineered skin made with superficial or deep dermal fibroblasts in order to determine any biomaterial-mediated anti-fibrotic influences on tissue engineered skin.

Fibrocytes participate in the development of heterotopic ossification.

Heterotopic ossification (HO) is a complication of musculoskeletal injury characterized by the formation of mature bone in soft tissues. The etiology of HO is unknown. We investigated the role of bone marrow derived progenitor cells in HO pathophysiology.

Fibrotic remodeling of tissue-engineered skin with deep dermal fibroblasts is reduced by keratinocytes.

Two-thirds of burn patients with deep dermal injuries are affected by hypertrophic scars, and currently, there are no clinically effective therapies. Tissue-engineered skin is a very promising model for the elucidation of the role of matrix microenvironment and biomechanical characteristics and could help in the identification of new therapeutic targets for hypertrophic scars. Conventionally, tissue-engineered skin is made of heterogeneous dermal fibroblasts and keratinocytes; however, recent work has shown that superficial and deep dermal fibroblasts are antifibrotic and profibrotic, respectively.

Superficial dermal fibroblasts enhance basement membrane and epidermal barrier formation in tissue-engineered skin: implications for treatment of skin basement membrane disorders.

Basement membrane is a highly specialized structure that binds the dermis and the epidermis of the skin, and is mainly composed of laminins, nidogen, collagen types IV and VII, and the proteoglycans, collagen type XVIII and perlecan, all of which play critical roles in the function and resilience of skin. Both dermal fibroblasts and epidermal keratinocytes contribute to the development of the basement membrane, and in turn the basement membrane and underlying dermis influence the development and function of the epidermal barrier. Disruption of the basement membrane results in skin fragility, extensive painful blistering, and severe recurring wounds as seen in skin basement membrane disorders such as epidermolysis bullosa, a family of life-threatening congenital skin disorders.

Deep dermal fibroblasts refractory to migration and decorin-induced apoptosis contribute to hypertrophic scarring.

Hypertrophic scar (HTS) represents the dermal equivalent of fibroproliferative disorders. Fibroblasts from the deep dermis are implicated in the development of HTS after injuries that involve deeper areas of the skin. However, fibroblasts that reside in the superficial layer of the skin show antifibrotic properties, and injuries limited to this area heal with little or no scarring.

Reduced decorin, fibromodulin, and transforming growth factor-β3 in deep dermis leads to hypertrophic scarring.

Hypertrophic scar (HTS) occurs after injuries involving the deep dermis, while superficial wounds (SWs) to the skin heal with minimal or no scarring. The levels of transforming growth factor (TGF)-β1 and small leucine-rich proteoglycans (SLRPs) with fibroblast subtype and function may influence the development of HTS. The aim of this study was to characterize the expression and localization of factors that regulate wound healing including SLRPs, TGF-β1, and TGF-β3 in an experimental human SW and deep wound (DW) scar model including fibroblasts from superficial and deep layers of normal dermis.

In vitro osteogenic induction of human gingival fibroblasts for bone regeneration.

Background And Objective: Periodontitis is an inflammatory disease causing bone loss, and is a primary cause of tooth loss. Gingival fibroblasts are readily available with minimal donor site morbidity and may be ideal for tissue engineering efforts in regenerating lost alveolar bone. Dexamethasone (Dex) is commonly employed for in vitro osteogenic induction of a variety of cells, but its effect on human gingival fibroblasts (HGF) is still controversial.

Differential collagen-glycosaminoglycan matrix remodeling by superficial and deep dermal fibroblasts: potential therapeutic targets for hypertrophic scar.

Skin substitutes are the preferred treatment option in the case of extensive skin loss following burns or other injuries. Among skin substitutes, cultured skin substitutes containing autologous fibroblasts and keratinocytes on collagen-glycosaminoglycan (C-GAG) matrix are most preferred for wound repair. A significant negative outcome of wound healing is hypertrophic scarring (HTS), a dermal fibroproliferative disorder, that leads to considerable morbidity.

Small leucine-rich proteoglycans, decorin and fibromodulin, are reduced in postburn hypertrophic scar.

Small leucine-rich proteoglycans (SLRPs) are extracellular matrix molecules that regulate collagen fibrillogenesis and inhibit transforming growth factor-β activity; thus, they may play a critical role in wound healing and scar formation. Hypertrophic scarring is a dermal form of fibroproliferative disorders, which occurs in over 70% of burn patients and leads to disfigurement and limitations in function. By understanding the cellular and molecular mechanisms that lead to scarring after injury, new clinical therapeutic approaches can by developed to minimize abnormal scar formation in hypertrophic scarring and other fibroproliferative disorders.

Use of real time three-dimensional transesophageal echocardiography in intracardiac catheter based interventions.

Background: Real-time three-dimensional (RT3D) echocardiography is a recently developed technique that is being increasingly used in echocardiography laboratories. Over the past several years, improvements in transducer technologies have allowed development of a full matrix-array transducer that allows acquisition of pyramidal-shaped data sets. These data sets can be processed online and offline to allow accurate evaluation of cardiac structures, volumes, and mass.

Spontaneous gallbladder perforation, pericholecystic abscess and cholecystoduodenal fistula as the first manifestations of gallstone disease.

Background: Gallstone disease is common, and complications that are frequently encountered include acute cholecystitis and acute pancreatitis, but rarely gallbladder perforation.

Method: Data were retrospectively collected from clinical case notes and a literature review is presented.

Results: A 72-year-old lady presented with spontaneous gallbladder perforation, pericholecystic abscess and cholecystoduodenal fistula as the first manifestations of gallstone disease.

Osteogenic response of bone marrow stromal cells from normal and ovariectomized rats treated with a low dose of basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) is a potent mitogen that exhibits stimulatory effects on bone tissue regeneration. To gain further insight into the potential of bFGF for systemic therapy in osteoporosis, we investigated the responsiveness of bone marrow stromal cells (BMSCs) explanted from 7-month-old normal and ovariectomized (OVX) rats that were intravenously treated with a low dose of bFGF (25 microg/kg) for 2 weeks. The BMSCs were obtained using femoral aspiration and maintained in an osteogenic medium.

Evaluation of the abdominal aorta and the renal arteries with an intracardiac echocardiography probe placed in the inferior vena cava: a feasibility study.

Background: Ultrasound evaluation of the abdominal aorta and its branches is usually performed transabdominally. Not infrequently, the image quality is suboptimal. Recently, an intracardiac echocardiography probe has become commercially available.

In vitro osteogenic response of rat bone marrow cells to bFGF and BMP-2 treatments.

Basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) are actively pursued for stimulation of bone formation. To assess their promise for systemic therapy of osteoporosis, we ascertained the effects of bFGF and BMP-2 on bone marrow cells in vitro. Bone marrow cells were obtained from young (8 weeks) and adult (32 weeks) rats by femoral aspiration and were exposed to osteogenic medium (ie, basal medium with 10 mM beta-glycerolphosphate and 100 nM dexamethasone) containing the growth factors.

Growth factor delivery for bone tissue repair: an update.

Growth factors (GFs) are endogenous proteins capable of acting on cell-surface receptors and directing cellular activities involved in the regeneration of new bone tissue. The specific actions and long-term effects of GFs on bone-forming cells have resulted in exploration of their potential for clinical bone repair. The concerted efforts have led to the recent approval of two GFs, bone morphogenetic protein-2 and osteogenic protein-1, for clinical bone repair, and human parathryroid hormone (1-34) for augmentation of systemic bone mass.