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The engineering of tracheal substitutes is pivotal in improving tracheal reconstruction. In this study, we aimed to investigate the effects of biomechanical stimulation on tissue engineering tracheal cartilage by mimicking the trachea motion through a novel radial stretching bioreactor, which enables to dynamically change the diameter of the hollow cylindrical implants. Applying our bioreactor, we demonstrated that chondrocytes seeded on the surface of Poly (ε-caprolactone) scaffold respond to mechanical stimulation by improvement of infiltration into implants and upregulation of cartilage-specific genes. Further, the mechanical stimulation enhanced the accumulation of cartilage neo-tissues and cartilage-specific extracellular macromolecules in the muscle flap-remodeled implants and reconstructed trachea. Nevertheless, the invasion of fibrous tissues in the reconstructed trachea was suppressed upon mechanical loading.

The regeneration capacity of knee cartilage can be enhanced by applying periosteal grafts, but this effect varies depending on the different sources of the periosteal grafts applied for cartilage formation. Tibia periosteum can be used to enhance cartilage repair. However, long-term analysis has not been conducted. The endochondral ossification capacity of tibia periosteum during cartilage repair also needs to be investigated. In this study, both vascularized and non-vascularized tibia periosteum grafts were studied to understand the relationship between tissue perfusion of the periosteum graft and the effects on cartilage regeneration and bone formation. Furthermore, anti-ossification reagents were added to evaluate the efficacy of the prevention of bone formation along with cartilage regeneration. A critical-size cartilage defect (4 × 4 mm) was created and was covered with an autologous tibia vascularized periosteal flap or with a non-vascularized tibia periosteum patch on the knee in the rabbit model. A portion of the vascularized periosteum group was also treated with the anti-osteogenic reagents Fulvestrant and IL1β to inhibit unwanted bone formation. Our results indicated that the vascularized periosteum significantly enhanced cartilage regeneration in the cartilage defect region in long-term treatment compared to the non-vascularized group. Furthermore, the addition of anti-osteogenic reagents to the vascularized periosteum group suppressed bone formation but also reduced the cartilage regeneration rate. Our study using vascularized autologous tissue to repair cartilage defects of the knee may lead to the modification of current treatment in regard to osteoarthritis knee repair.

Iron, the most abundant transition metal ion in humans, participates in the biosynthesis, translocation, signal transduction, and transformation of nitric oxide through its encapsulation in the form of heme, [Fe-S], and [Fe(NO)2] cofactors within a variety of enzymes and proteins. After the review on nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC) for the biosynthesis and detection of NO, in this report, we discuss the natural utilization of the [Fe(NO)2] motif for translocation of endogenous NO and the translational development of synthetic dinitrosyl iron complexes (DNICs) for biomedical applications. A mechanistic study of NO-release and NO-transfer reactivity of structure-characterized DNICs promoted the discovery of cell-penetrating and in vivo NO-delivery reactivity for treatment of cancer and wound healing in diabetes. Beyond activation of sGC and vasodilation, phase I/II clinical trials of glutathione-bound DNICs (Oxacom®) against hypertension encourage bioinorganic engineering of DNICs into scaffolds for tissue regeneration and repair relying on anti-bacterial, anti-inflammation, cytoprotective, and proliferative effects of NO.

Periosteal osteogenic capacity can be exploited to enhance bone formation in the fields of tissue engineering and regenerative medicine. Despite this importance, there have been no studies examining the composition, structure, and osteogenic capacity of periostea from different bone sources. In this study, structure and osteogenic factor content were compared among periostea from rib, calvarial, femoral, and tibial bones, in which the native bones of these four regions were harvested and subjected to histological analysis. The osteogenic capacity of grafted periosteum was evaluated using an in vivo vascularized pedicle model of bone tissue engineering. Poly(ethylene glycol)-poly(l-lactic acid) (PEG-PLLA) copolymer hydrogels were seeded with bone marrow mesenchymal stem cells and implanted with grafted periosteum harvested from either calvarial or tibial bone, which were representative of thin and thick native periostea, respectively. The cambium layer thickness of periostea from the femoral and tibial bones (36.9% ± 2.5% and 36.8% ± 2.6%) was greater than that from the calvarial and rib bones (26.8% ± 2.4% and 25.5% ± 1.9%). The osteocalcin and alkaline phosphatase levels were comparatively higher in the femoral and tibial periostea than those in periostea harvested from the calvarial and rib bones. The construct implanted with grafted tibial periosteum resulted in greater neo-bone regeneration and higher osteocalcin and alkaline phosphatase expression. This study is the first investigation of the osteogenic capacity of periostea from diverse sources. The results can be used to guide clinical strategies that exploit periostea for tissue engineering and clinical applications.

Reconstruction of large skeletal defects is challenging due to the requirement for large volumes of donor tissue and the often complex surgical procedures. Tissue engineering has the potential to serve as a new source of tissue for bone reconstruction, but current techniques are often limited in regards to the size and complexity of tissue that can be formed. Building tissue using an in vivo bioreactor approach may enable the production of appropriate amounts of specialized tissue, while reducing issues of donor site morbidity and infection. Large animals are required to screen and optimize new strategies for growing clinically appropriate volumes of tissues in vivo. In this article, we review both ovine and porcine models that serve as models of the technique proposed for clinical engineering of bone tissue in vivo. Recent findings are discussed with these systems, as well as description of next steps required for using these models, to develop clinically applicable tissue engineering applications.

Current clinical treatments on lymphedema provide promising results, but also result in donor site morbidities. The establishment of a microenvironment optimized for lymphangiogenesis can be an alternative way to enhance lymphatic tissue formation. Hemodynamic flow stimuli have been confirmed to have an influential effect on angiogenesis in tissue engineering, but not on lymphatic vessel formation. Here, the three in vivo scaffolds generated from different blood stimuli in the subcutaneous layer, in the flow through pedicle, and in an arterio-venous (AV) loop model, were created to investigate potential of lymphangiogenesis of scaffolds containing lymphatic endothelial cells (LECs). Our results indicated that AV loop model displayed better lymphangiogenesis in comparison to the other two models with slower flow or no stimuli. Other than hemodynamic force, the supplement of LECs is required for lymphatic vessel regeneration. The in vivo scaffold generated from AV loop model provides an effective approach for engineering lymphatic tissue in the clinical treatment of lymphedema. [ABSTRACT FROM AUTHOR]

Iron, the most abundant transition metal ion in humans, participates in the biosynthesis, translocation, signal transduction, and transformation of nitric oxide through its encapsulation in the form of heme, [Fe–S], and [Fe(NO)2] cofactors within a variety of enzymes and proteins. After the review on nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC) for the biosynthesis and detection of NO, in this report, we discuss the natural utilization of the [Fe(NO)2] motif for translocation of endogenous NO and the translational development of synthetic dinitrosyl iron complexes (DNICs) for biomedical applications. A mechanistic study of NO-release and NO-transfer reactivity of structure-characterized DNICs promoted the discovery of cell-penetrating and in vivo NO-delivery reactivity for treatment of cancer and wound healing in diabetes. Beyond activation of sGC and vasodilation, phase I/II clinical trials of glutathione-bound DNICs (Oxacom®) against hypertension encourage bioinorganic engineering of DNICs into scaffolds for tissue regeneration and repair relying on anti-bacterial, anti-inflammation, cytoprotective, and proliferative effects of NO. [ABSTRACT FROM AUTHOR]