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Skin grafts, including skin flaps, are widely used in plastic and reconstructive surgery to cover wounds and tissue defects resulting from mechanic or burn injury. Ischemic necrosis is the main complication in skin graft surgery due to inefficient revascularization. Though the surgical delay procedure has been proved to be the only effective technique to prevent skin flap ischemic necrosis by mechanism of inducing adaption to hypoxia, but it is time consuming, costly, and having high risk of infection due to repeated surgery. Recent research demonstrated that, in addition to protecting cells against apoptosis, the expression of survivin correlates with intratumoral microvessel density in several different types of tumors and survivin could upregulate several proangiogenic factors, including VEGF, Egr-1 and Siah-1. Moreover, Survivin DeltaEx3, one of the survivin alternative splice variants, is necessary for activating the small GTPase Rac1 during endothelial tube formation and required for in vivo endothelial cell invasion. Therefore, we postulate that intracellular delivery of survivin or Survivin DeltaEx3 by fusion with protein transduction domain would enhance skin flap survival through accelerating revascularization by both inhibiting the apoptosis of microvascular endothelial cells and promoting skin flap angiogenesis. If the hypothesis was proved to be practical, the fusion proteins would be widely used in plastic and reconstructive surgery to prevent skin flap from ischemic necrosis in the future.

Hypoxia is a common phenomenon in human solid tumors and has been considered as an important, independent negative prognostic factor for response to treatment and survival of tumor patients. Hypoxia-inducible factor-1 (HIF-1) is the central transcription factor which is activated by hypoxia and modulates the expression of many genes involved in cell metabolism, proliferation, apoptosis, angiogenesis. Recently, it has been reported that HIF-1 contributes to tumor radioresistance by upregulating survivin expression under hypoxic conditions. Moreover, in hypoxic tumor cells, HIF-1 dependent signal transduction pathway is activated and could be further enhanced by radiation, thereby providing survival signals to adjacent vascular endothelial cells by upregulation of VEGF and bFGF and resulting in tumor radioresistance through vascular radioprotection. Recent research revealed that the stability of HIF-1alpha, one of the two subunits of HIF-1, determines the whole HIF-1 activity and the C-terminal transactivation domain of HIF-1alpha could reduce HIF-1 activity when overexpressed in tumor cells by disruption of the assembly of HIF-1 transcription complex. Therefore, we postulate that fusion with protein transduction domains would overcome the inability of C-terminal transactivation domain of HIF-1alpha to cross cellular membrane. Thus the recombinant fusion proteins could serve as cell-permeable HIF-1 antagonists, function as both inhibitors of tumor angiogenesis and tumor radiosensitizers, and would be widely used in clinical settings to improve tumor response to radiotherapy.

In recent years, a large number of researchers have paid much attention on small interfering RNA (siRNA) after the advent of RNA interference technology, which has been harnessed as an efficient way of sequence-specific gene silencing in gene therapy, enables elucidation of gene functions, and the identification of new drug targets. Despite tremendous progress has been made in novel delivery systems and vectors via formulation of polyplexes and conjugations, such as cationic polymers (LPEI, BPEI), cationic liposome (DOTAP), peptides (CPP), unmet needs still exist. Many cationic agents used for condensing siRNA often exhibits severe cytotoxicity, which limits clinical applications, and is obliged to be handled. Thus great interest in searching for novel and sophisticated polymeric vectors has been spurred. Herein we proposed a genetically synthetic protein-based polymer, which is also referred to as elastin-like polypeptides (ELPs) excerpted from human tropoelastin highly repetitive sequence, Val-Pro-Gly-Xaa-Gly, where the "guest residue" Xaa is any amino acid except Pro. Thus, if we alternate the "guest residue" Xaa to Lys or Arg, to a significant extent, it can emerge as a powerful cationic polymer for siRNA delivery carrier, and hopefully it will be put into practice in the near future.

Due to the limited regenerative capacity of cartilage tissues, articular cartilage defect caused by various lesions remains a problem to be resolved. Tissue engineering provided a valuable alternative to current therapeutic approaches, which is expected to greatly reduce the need of joint replacement. Scaffold, acting as cell carrier, plays an important role in maintaining cells in defect sites, thus facilitates the chondrogenesis. However, an open operation is often needed to implant the cell/scaffold composite, to find a less invasive way to delivering the complex into the defect site would be desirable. Different from synthetic and other nature derived scaffold, platelet-rich plasma (PRP) is a fraction of plasma which contains multiple growth factors and could be clotted when mixed with thrombin. Therefore, we hypothesized that PRP could be used as an autologous cell carrier to inject and fix chondrocytes into the defect site of articular cartilage. With the assistance of arthroscope, the defect could be precisely located, and injectable PRP-Cell composite would make the operation micro-invasive and simple.

The affected individual of hair loss demands help, because hair is viewed as a sign of youth and good health. Nowadays treatment of alopecia includes drug therapy and hair transplantation. Some drugs may promote hair growth, at least temporarily, but the treatment is effective only in milder alopecia, instead of extensive alopecia. Furthermore, the side effect of long period medication could not be avoided. Hair transplantation involves harvesting small pieces of hair-bearing scalp grafts from a donor site and relocating them to a bald area. This method does not increase the number of existing hairs, but only redistributes them. The operation is sophisticated and time-consuming, thus the patient suffers a lot during the process. The discovery of hair follicle stem cells (FSC) brings gospel to the affected individual of hair loss because of its capacity of generating new hair when they interact with mesenchymal dermal papilla cells (DPC). Besides, both FSC and DPC have strong proliferative capacity and the patient's own cells could be expanded considerably in vitro. Thus we hypothesize that the microencapsulation of the two kinds of cells in alginate gels could be implanted into the bald scalp of the patient since alginate gels is effective in cell transplantation. The strategy may provide a more convenient and valid alternative to hair loss if the hypothesis proved to be practical.