Photo-crosslinkable amniotic membrane hydrogel for skin defect healing.

The human amniotic membrane (HAM) collagen matrix derived from human placenta can be decellularized (dHAM) to form a natural biocompatible material. dHAM has different bioactive substances and has been used widely in human tissue engineering research. However, dHAM has some disadvantages, e.g., poor mechanical properties, easy degradation and inconvenient operation and use, so it is not conducive to large-area or full-thickness skin defect healing. To overcome these limitations, for the first time, dHAM was grafted with methacrylic anhydride (MA) to form photocrosslinked dHAM methacrylate (dHAMMA); dHAMMA was then blended with methacrylated gelatin (GelMA), followed by the addition of a photosensitizer for photocrosslinking to obtain the fast-forming GelMA-dHAMMA composite hydrogel. Further, GelMA-dHAMMA was found to have the porous structure of a bicomponent polymer network and good physical and chemical properties. In vitro experiments, GelMA-dHAMMA was found to promote fibroblast proliferation and α-smooth muscle actin (α-SMA) expression. In vivo investigations also demonstrated that GelMA-dHAMMA promotes wound collagen deposition and angiogenesis, and accelerates tissue healing. GelMA-dHAMMA inherits the good mechanical properties of GelMA and maintains the biological activity of the amniotic membrane, promoting the reconstruction and regeneration of skin wounds. Thus, GelMA-dHAMMA can serve as a promising biomaterial in skin tissue engineering. STATEMENT OF SIGNIFICANCE: Since the early 20th century, the human amniotic membrane (HAM) has been successfully used for trauma treatment and reconstruction purposes. dHAM has different bioactive substances and has been used widely in human tissue-engineering research. In this work, the dHAM and gelatin were grafted and modified by using methacrylic anhydride (MA) to form photocrosslinked dHAMMA and methacrylated gelatin (GelMA). Then, the dHAMMA and GelMA were blended with a photosensitizer to form the GelMA-dHAMMA composite hydrogel derived from gelatin-dHAM. GelMA-dHAMMA exhibits a bicomponent-network (BCN) interpenetrating structure. dHAM dydrogel has advantages, e.g., good mechanical properties, slow degradation and convenient operation, so it is conducive to large-area or full-thickness skin defect healing.

Mechanical on-off gates for regulation of drug release in cutaneous or musculoskeletal tissue repairs.

Drug release synchronized with tissue motion is attractive to cutaneous or musculoskeletal tissue injury repair. Here, we have developed a method of regulating drug release by mechanical on-off gates for potential treatment of repeated injury in these tissues. The mechanical gates consisted of a multilayer structure: A brittle outmost layer adhered to an elastic middle layer, which wrapped an inmost drug carrier to form the composite multilayer structure. When it was stretched, cracks appeared as mechanical gates due to mechanical performance difference between the outmost layer and the middle layer, leading to the drug release. When the external force disappeared, it recovered to stop the drug release. The controlled drug release would therefore be achieved by changing the status (opening or closure) of mechanical gates through applying this on-off mechanical stretching. A prototype based on the composite multilayer structure of adhesive coating and electrospinning technique realized the controlled release of drug and effectively repaired the incision. More types of composite multilayer structures for mechanical drug release were expected to meet curing requirement in cutaneous or musculoskeletal tissues.

Development of a visible light, cross-linked GelMA hydrogel containing decellularized human amniotic particles as a soft tissue replacement for oral mucosa repair.

Early effective treatment of oral mucosal defects is the key to ensuring defect healing and functional recovery. The application of human amniotic membrane (HAM) in promoting wound healing has been shown to be safe and effective. However, amniotic membrane is thin, easy to tear and difficult to handle. Combined with the natural forces at play in the oral cavity, this has restricted the clinical applications of HAM for healing of mucosal defects. Methacrylated gelatin (GelMA) has good mechanical strength and adhesion, and can be used as a bionic repair film to attach to the damaged surface of oral mucosa, but GelMA lacks bioactive substances and cannot promote the rapid repair of oral mucosal defects. The aim of this study was to design a type of composite GelMA hydrogel mixed with decellularized human amniotic particles (dHAP) as an oral mucosa substitute, to promote regeneration of defective mucosa by stimulating rapid angiogenesis. The composite substitute GelMA-dHAP was easy to synthesize and store, and easy to operate for repair of oral mucosal defects. We show the angiogenic potential of GelMA-dHAP on chick chorioallontoic membrane and the curative effect of GelMA-dHAP as a treatment in the rabbit oral mucosa defect model. In conclusion, this study confirms the effectiveness of GelMA-dHAP as an ideal soft tissue substitute for the repair of oral mucosal defects, overcoming the shortcomings of using HAM or GelMA alone.

Advanced biomaterials for repairing and reconstruction of mandibular defects.

Mandibles are the largest and strongest bone in the human face and are often severely compromised by mandibular defects, compromising the quality of life of patients. Mandibular defects may result from trauma, inflammatory disease and benign or malignant tumours. The reconstruction of mandibular defect has been a research hotspot in oral and maxillofacial surgery. Although the principles and techniques of mandibular reconstruction have made great progress in recent years, the development of biomedical materials is still facing technical bottleneck, and new materials directly affect technological breakthroughs in this field. This paper reviews the current status of research and application of various biomaterials in mandibular defects and systematically elaborates different allogeneic biomaterial-based approaches. It is expected that various biomaterials, in combination with new technologies such as digital navigation and 3D printing, could be tuned to build new types of scaffold with more precise structure and components, addressing needs of surgery and post-reconstruction. With the illustration and systematization of different solutions, aims to inspire the development of reconstruction biomaterials.

Triple-controlled oncolytic adenovirus expressing melittin to exert inhibitory efficacy on hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant disease, and its outcome of routine therapies is poor. Comprehensive treatment including gene therapy is an important way to improve patients' prognosis and survival. In this study, we successfully constructed a triple-controlled cancer-selective oncolytic adenovirus, QG511-HA-Melittin, carrying melittin gene, in which the hybrid promoter, hypoxia-response element (HRE)-AFP promoter, was used to control viral E1a expression targeting AFP-positive cancer cells in hypoxia microenviroment, and the E1b-55 kDa gene was deleted in cancer cells with p53-deficiency. The cytological experiments found that the viral replication of QG511-HA-Melittin was increased to 12800-folds in Hep3B cells within 48 h, and 130-folds in SMMC-7721, but the virus did not replicate in L-02 cells. QG511-HA-Melittin had a strong inhibition effect on AFP-positive HCC cell proliferation, such as Hep3B and HepG2, whereas, there was low or no inhibition effect of QG511-HA-Melittin on AFP-negative cancer cells SMMC-7721 and normal cells L-02. In the in vivo experiment, compared with the blank control group, QG511-HA-Melittin can significantly inhibit the growth of HCC xenografts (P<0.05). The survival of mice in QG511-HA-Melittin group was much longer than that of the blank control group. Both in vitro and in vivo experiments manifested that QG511-HA-Melittin exerts an inhibitory effect on HCC cells, which may provide a new strategy for HCC biotherapy.