Reconstructing vascular networks promotes the repair of skeletal muscle following volumetric muscle loss by pre-vascularized tissue constructs.

Current treatment for complex and large-scale volumetric muscle loss (VML) injuries remains a limited success and have substantial disadvantages, due to the irreversible loss of muscle mass, slow muscle regeneration, and rapid formation of non-functional fibrosis scars. These VML injuries are accompanied by denervation and the destruction of native vasculature which increases difficulties in the functional restoration of muscle. Here, reconstruction of the vascular network at the injury site was offered as a possible solution for improving the repair of muscle defects through the timely supply of nutrients and oxygen to surrounding cells. A hydrogel-based tissue construct containing various densities of the vascular network was successfully created in the subcutaneous space of mice by manipulating hydrogel properties, and then implanted into the VML injury site. One month after implantation, the mouse treated with the highly vascularized tissue had extensive muscle repair at the injury site and only spent a shorter time completing the inclined plane tests. These findings suggest that the reconstruction of the functional vascular network at the VML injury site accelerated muscle fiber repair through a timely supply of sufficient blood and avoided invasion by host fibroblasts.

Comparison of Dental Surface Image Registration and Fiducial Marker Registration: An In Vivo Accuracy Study of Static Computer-Assisted Implant Surgery.

This study compared the accuracy of static computer-assisted implant surgery (sCAIS) planned through dental surface image registration and fiducial marker registration. Stone models of 30 patients were converted into digital dental casts by using a desktop scanner. Cone-beam computed tomography (CBCT) was performed and superimposed to the digital dental casts with two methods: matching the dental surface images or matching the fiducial markers on a stereolithographic radiographic template. Following the implant planning, stereolithographic surgical guides were fabricated, and 56 fully guided implants were inserted by the same doctor. Deviations between planned and inserted implants were measured and compared using postoperative CBCT images. After adjustment for other potential influencing factors, compared with the fiducial marker registration group, significantly larger mean lateral deviations were noted in the dental surface registration group at both the implant platform and apex (p = 0.0188 and 0.0371, respectively). However, the mean lateral deviations for the dental surface registration (0.83 ± 0.51 mm at implant platform and 1.24 ± 0.68 mm at implant apex) were comparable to the literature. In conclusion, our findings indicate that although sCAIS planned using dental surface image registration was not statistically as accurate as that using fiducial marker registration, its accuracy was satisfactory for clinical use.

Two-Stage Patterned Cell-Based Treatments for Skin Regeneration.

During the process of wound healing, avoiding the formation of aligned collagen fibrils and subsequent scarring has become the focus of numerous research efforts. However, the goal of regeneration of native or scar-free skin remains a challenge. The complex and equivocal connection between inflammation and regeneration within the process of healing contributes to unsatisfactory treatment outcomes. Inspired by the scarless repair observed in fetal wound healing, we create a two-stage treatment combining the hydrocolloid dressing to attenuate the immune response in the initial three days, and the biomimetic cell-laden hydrogel to improve skin regeneration, which meet the specific needs of each stage in the healing process. To further accelerate the skin regeneration, the patterned cell-laden hydrogels were fabricated by photo-mask based photolithography technique. The efficacy and possible mechanisms of skin regeneration using this patterned cell-laden hydrogel therapy was investigated. Results show that these two-stage patterned cell-laden treatments were able to promote vascular network formation, accelerate wound closure, decrease scar formation, increase tissue regeneration and restore structure and mechanical properties of the skin in a full-thickness murine wound model. These data suggest that our patterned cell-based two-stage treatments can be used as a promising therapeutic option for wound healing by accelerating skin tissue regeneration.

A comparison of the bone regeneration and soft-tissue-formation capabilities of various injectable-grafting materials in a rabbit calvarial defect model.

Restoring adequate blood supply is essential to the success of bone repair and augmentation procedures in craniofacial surgery. Nevertheless, the manner by which the incorporation of collagen gels (which can potentially induce angiogenesis), particulated deproteinized bovine bone grafts, or a combination of both can accelerate or delay bone regeneration in a clinical setting remains controversial. The objective of this study was to evaluate radiographically and histologically the capacity and functionality of particulated bone grafts and collagen gels on bone ossification and soft tissue formation in a rabbit calvarial defect. Bilateral calvarial defects in adult white New Zealand rabbits were filled or left either unfilled with bone grafts (DBBM), collagen gels (Gel), or a combination of both (DBBM + Gel). The defects were allowed to heal for 1, 2, and 6 months postoperatively before termination. Healing and regeneration patterns were assessed by 3D µCT and histological methods, and the biomechanical properties of regenerated tissue constructs were investigated and compared with autogenous calvarial bone. Results show that implanted DBBM and DBBM + Gel significantly enhanced immature bone formation compared with the empty and Gel groups; the latter treatment improved soft tissue formation and impeded immature bone formation but yielded no significant effect on mature bone formation. Implantation of DBBM not only effectively reconstructed 188.83 ± 25.25% of the tissue volume of the original defect, but it also regenerated bone tissue with similar tissue composition and biomechanical properties as the original autogenous bone. We also show that implanting different biomaterials can control the composition of soft and hard tissue in reconstructed tissue constructs in calvarial bone defects. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 529-544, 2019.

Dehydroepiandrosterone attenuates allergic airway inflammation in Dermatophagoides farinae-sensitized mice.

Dehydroepiandrosterone, an androgen abundant in circulation, has important immunomodulating effects. In this study the therapeutic effect of dehydroepiandrosterone on established allergic inflammation was examined in a dust mite (Dermatophagoides farinae)-induced asthma model. Airway inflammation was provoked in D. farinae-sensitized BALB/c mice by repetitive intratracheal challenge (3 times, once a week). Three days after the first challenge, mice were fed a diet incorporated with 1.5% (w/w) dehydroepiandrosterone and were examined at days 3 and 6 after the last challenge. Airway challenge resulted in pulmonary eosinophilic inflammation accompanied by elevated blood eosinophil counts and elevated serum and bronchoalveolar lavage immunoglobulin E antibody levels in control diet-fed mice. However, the D. farinae-induced airway inflammation and blood eosinophilia was significantly reduced in dehydroepiandrosterone-fed mice, which was associated with a decrease in serum interleukin-4, interleukin-5, and interferon-gamma levels. Total immunoglobulin E antibody concentrations in serum and bronchoalveolar lavage fluids were not affected by the dehydroepiandrosterone treatment. These results demonstrated that dehydroepiandrosterone could suppress preexisting allergic airway inflammation.

Activation of mast cells is essential for development of house dust mite Dermatophagoides farinae-induced allergic airway inflammation in mice.

In this study, we demonstrate that Dermatophagoides farinae (Der f), a major source of airborne allergens, but not OVA, could rapidly activate mast cells in mice. This was indicated by an elevation of serum mouse mast cell protease 1, a mast cell-specific proteinase, as early as 30 min after intratracheal challenge. Administration of sodium cromoglycate (40 mg/kg, i.p., 1 h before Der f instillation), a mast cell stabilizer, not only suppressed acute mouse mast cell protease 1 production but also attenuated the allergic airway inflammation provoked by repetitive Der f challenge in mice (five times at 1-wk interval). Der f induced the expression of mRNA for TNF-alpha, IL-1beta, IL-4, IL-6, IL-9, and IL-13 in mastocytoma P815 cells and stimulated both P815 cells and bone marrow-derived mast cells to produce IL-4, IL-6, and TNF-alpha in a dose- and time-dependent manner. Cycloheximide as well as sodium cromoglycate blocked the Der f-induced IL-4 production, indicating a de novo protein synthesis process. Supernatants of Der f-stimulated mast cells chemoattracted monocytes and T lymphocytes; they up-regulated the expression of costimulatory B7 molecules, eotaxin, RANTES, monocyte chemoattractant protein 1, and IFN-inducible protein 10 mRNA of alveolar macrophages; they supported PHA-induced T cell proliferation; and they promoted Th2 cell development. Our data indicate that mast cells may be an important cell type during the initiation of Der f sensitization in the airway by modulating the function of alveolar macrophages and T cells.

House dust mite Dermatophagoides farinae augments proinflammatory mediator productions and accessory function of alveolar macrophages: implications for allergic sensitization and inflammation.

In this study, we examine the effects of Dermatophagoides farinae (Der f), a major source of airborne allergens, on alveolar macrophages (AMs), and we also test its contribution to allergic responses in mice. Der f activated NF-kappaB of AMs and, unlike OVA or LPS stimulation, up-regulated IL-6, TNF-alpha, and NO. In addition, it down-regulated antioxidants, but affected neither the expression nor production of IL-12. Der f-stimulated AMs expressed enhanced levels of costimulatory B7 molecules, supported T cell proliferation, and promoted Th2 cell development. The enhanced accessory function was suppressed by blockade mAbs to B7.2, IL-6, and TNF-alpha and by N-monomethyl-L-arginine, an NO synthase inhibitor, and N-acetylcysteine, a thiol antioxidant, whereas it was augmented by (+/-)-S-nitroso-N-acetylpenicillamine, an NO donor. Arg-Gly-Asp-Ser peptide and neo-glycoproteins galactose-BSA and mannose-BSA inhibited the Der f-induced IL-6 and TNF-alpha productions and enhanced accessory function of AMs. Der f was more potent than OVA for inducing pulmonary eosinophilic inflammation, NO, and serum allergen-specific IgG1 Ab production in mice. AMs from Der f-challenged mice expressed enhanced levels of B7 and augmented T cell proliferation ex vivo. In Der f-challenged mice, respiratory syncytial virus infection (5 x 10(5) pfu; 3 days before Der f instillation) augmented Der f-specific Ab production, whereas dexamethasone (50 mg/kg; 1 h before Der f instillation) diminished the allergic airway inflammation and Ab response. We conclude that AMs are sensitive targets for Der f and that the Der f-induced proinflammatory responses may represent an important mechanism in mediating the development of allergic sensitization and inflammation.