Background The benefits of radiotherapy (RT) for cancer have been well documented for many years. However, even with targeted radiation delivery, many patients treated with radiation develop adverse effects. The purpose of this review was to analyze the current research into the biological basis of RT-induced normal tissue damage. Methods The PubMed and EMBASE databases were reviewed for articles on adverse effects of RT on normal tissue published from January 2005 through May 2012. Subsequently, abstracts of these articles were reviewed to identify articles with information relevant to the biological basis of RT-induced DNA damage and DNA repair. In addition, reference lists of the articles identified by the database search were reviewed, and referenced articles that seemed relevant were reviewed with no limitations on publication date. Results The database searches yielded 1751 publications. Of these, 1729 were eliminated because they did not address fundamental biology or were duplicates. A total of 22 articles were included. These articles revealed that many adverse effects are driven by chronic oxidative stress that affects the nuclear function of DNA repair mechanisms. Among normal cells undergoing replication, cells in S phase are most radioresistant because of overexpression of DNA repair enzymes, while cells in M phase are especially radiosensitive. Cancer cells exhibit increased radiosensitivity due to a breakdown in cell cycle checkpoints and repair mechanisms, and this increased radiosensitivity leads to accumulation of irreparable DNA lesions and cell death. Irradiated cells have an indirect effect on the cell cycle and survival of co-cultured non-irradiated cells. Method of irradiation and linear energy transfer to cancer cells versus bystander cells is shown to have an effect on cell survival, both cancerous and healthy. Conclusions RT-induced increases in reactive oxygen species in irradiated cells may signal healthy cells by increasing metabolic stress and creating DNA lesions. While normal cells express a strong ability to repair RT-induced DNA lesions, the side effects of RT and bystander cell signaling may have a larger impact than previously acknowledged.

Adipose tissue harvested from the abdomen through direct excision or Coleman's technique with centrifugation was found to yield the most SVF cells and ASCs.

Nanoparticle-based drug delivery systems are appealing because, among other properties, they are easily manufactured and have the capacity to encapsulate a wide variety of drugs, many of which are not directly miscible with water. This review classifies nanoparticles into three broad categories based upon material composition: bio-inspired systems, synthetic systems, and inorganic systems. Each has distinct properties suitable for drug delivery applications, including their structure, composition, and pharmacokinetics (including clearance and uptake mechanisms), making each uniquely suitable for certain types of drugs. Furthermore, nanoparticles can be customized, making them ideal for a variety of applications. Advantages and disadvantages of the different systems are discussed. Strategies for improving nanoparticle efficacy include adding targeting agents on the nanoparticle surface, altering the degradation profile to control drug release, or PEGylating the surface to increase circulation times and reduce immediate clearance by the kidneys. The future of nanoparticle systems seems to be focused on further improving overall patient outcome by increasing delivery accuracy to the target area.

Insufficient neovascularization is associated with high levels of resorption and necrosis in autologous and engineered fat grafts. We tested the hypothesis that incorporating angiogenic growth factor into a scaffold–stem cell construct and implanting this construct around a vascular pedicle improves neovascularization and adipogenesis for engineering soft tissue flaps. Poly(lactic-co-glycolic-acid/polyethylene glycol (PLGA/PEG) microspheres containing vascular endothelial growth factor (VEGF) were impregnated into collagen-chitosan scaffolds seeded with human adipose-derived stem cells (hASCs). This setup was analyzed in vitro and then implanted into isolated chambers around a discrete vascular pedicle in nude rats. Engineered tissue samples within the chambers were harvested and analyzed for differences in vascularization and adipose tissue growth. In vitro testing showed that the collagen-chitosan scaffold provided a supportive environment for hASC integration and proliferation. PLGA/PEG microspheres with slow-release VEGF had no negative effect on cell survival in collagen-chitosan scaffolds. In vivo, the system resulted in a statistically significant increase in neovascularization that in turn led to a significant increase in adipose tissue persistence after 8 weeks versus control constructs. These data indicate that our model—hASCs integrated with a collagen-chitosan scaffold incorporated with VEGF-containing PLGA/PEG microspheres supported by a predominant vascular vessel inside a chamber—provides a promising, clinically translatable platform for engineering vascularized soft tissue flap. The engineered adipose tissue with a vascular pedicle could conceivably be transferred as a vascularized soft tissue pedicle flap or free flap to a recipient site for the repair of soft-tissue defects.

Aligned three-dimensional nanofibrous silk fibroin-chitosan (eSFCS) scaffolds were fabricated using dielectrophoresis (DEP) by investigating the effects of alternating current frequency, the presence of ions, SF:CS ratio, and post-DEP freezing temperature. Scaffolds were characterized with polarized light microscopy (PLM) to analyze SF polymer chain alignment, atomic force microscopy (AFM) to measure the apparent elastic modulus, and scanning electron microscopy and AFM to analyze scaffold topography. The interaction of human umbilical vein endothelial cells (HUVECs) with eSFCS scaffolds was assessed using immunostaining to assess cell patterning and AFM to measure the apparent elastic modulus of the cells. The eSFCS (50:50) samples prepared at 10 MHz with NaCl had the highest percentage of aligned area as compared to other conditions. As DEP frequency increased from 100 kHz to 10 MHz fibril sizes decreased significantly. eSFCS (50:50) scaffolds fabricated at 10 MHz in the presence of 5 mM NaCl had a fibril size of 77.96 ± 4.69 nm and an apparent elastic modulus of 39.9 ± 22.4 kPa. HUVECs on eSFCS scaffolds formed aligned and branched capillary-like vascular structures. The elastic modulus of HUVEC cultured on eSFCS was 6.36 ± 2.37 kPa. DEP is a potential tool for fabrication of SFCS scaffolds with aligned nanofibrous structures that can guide vasculature in tissue engineering and repair.

Adipose-derived stem cells (ASCs) facilitate wound healing by improving cellular and vascular recruitment to the wound site. Therefore, we investigated whether ASCs would augment a clinically relevant bioprosthetic mesh-non-cross-linked porcine acellular dermal matrix (ncl-PADM)-used for ventral hernia repairs in a syngeneic animal model. ASCs were isolated from the subcutaneous adipose tissue of Brown Norway rats, expanded, and labeled with green fluorescent protein. ASCs were seeded (2.5 · 10 4 cells/cm 2 ) onto ncl-PADM for 24 h before surgery. In vitro ASC adhesion to ncl-PADM was assessed at 0.5, 1, and 2 h after seeding, and cell morphology on ncl-PADM was visualized by scanning electron microscopy. Ventral hernia defects (2 · 4 cm) were created and repaired with ASC-seeded (n = 31) and control (n = 32) ncl-PADM. Explants were harvested at 1, 2, and 4 weeks after surgery. Explant remodeling outcomes were evaluated using gross evaluation (bowel adhesions, surface area, and grade), histological analysis (hematoxylin and eosin and Masson's trichrome staining), immunohistochemical analysis (von Willebrand factor VIII), fluorescent microscopy, and mechanical strength measurement at the tissue-bioprosthetic mesh interface. Stem cell markers CD29, CD90, CD44, and P4HB were highly expressed in cultured ASCs, whereas endothelial and hematopoietic cell markers, such as CD31, CD90, and CD45 had low expression. Approximately 85% of seeded ASCs adhered to ncl-PADM within 2 h after seeding, which was further confirmed by scanning electron microcopy examination. Gross evaluation of the hernia repairs revealed weak omental adhesion in all groups. Ultimate tensile strength was not significantly different in control and treatment groups. Conversely, elastic modulus was significantly greater at 4 weeks postsurgery in the ASC-seeded group ( p < 0.001). Cellular infiltration was significantly higher in the ASC-seeded group at all time points ( p < 0.05). Vascular infiltration was significantly greater at 4 weeks postsurgery in the ASC-seeded group ( p < 0.001). The presence of ASCs improved remodeling outcomes by yielding an increase in cellular infiltration and vascularization of ncl-PADM and enhanced the elastic modulus at the ncl-PADM-tissue interface. With the ease of harvesting adipose tissues that are rich in ASCs, this strategy may be clinically translatable for improving ncl-PADM ventral hernia repair outcomes.

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