Directed assembly of cell-laden hydrogels for engineering functional tissues

Tissue engineering aims to develop functionalized tissues for organ replacement or restoration. Biodegradable scaffolds have been used in tissue engineering to support cell growth and maintain mechanical and biological properties of tissue constructs. Ideally cells on these scaffolds adhere, proliferate and deposit matrix at a rate that is consistent with scaffold degradation. However, the cellular rearrangement within these scaffolds often does not recapitulate the architecture of the native tissues. Directed assembly of tissue-like structures is an attractive alternative to scaffold-based approach for tissue engineering which potentially can build tissue constructs with biomimetic architecture and function. In directed assembly, shape-controlled microstructures are fabricated in which organized structures of different cell types can be used as tissue building blocks. To fabricate tissue building blocks, hydrogels are commonly used as biomaterials for cell encapsulation to mimic the matrix in vivo. The hydrogel-based tissue building blocks can be arranged in pre-defined architectures by various directed tissue assembly techniques. In this paper, recent advances in directed assembly-based tissue engineering are summarized as an emerging alternative to meet challenges associated with scaffold-based tissue engineering and future directions are addressed

Role and regulation of growth plate vascularization during coupling with osteogenesis in tibial dyschondroplasia of chickens

Abstract Tibial dyschondroplasia (TD) is the most-prevalent leg disorder in fast-growing chickens; it is intractable and characterized by abnormal endochondral bone formation of proximal tibial growth-plates (TGPs). Previous studies have shown that bone is a highly vascularized tissue dependent on the coordinated coupling between angiogenesis and osteogenesis, but the underlying mechanisms of bone formation and bone remodeling are poorly defined in TD chickens. Here, we observed that inhibition of vasculogenesis and angiogenesis remarkably impaired vascular invasion in the hypertrophic chondrocyte zone of the TGPs, resulting in the massive death of chondrocytes due to a shortage of blood vessels and nutrients. Moreover, the balance of the OPG (osteoprotegerin)/RANKL (receptor activator of nuclear factor-kB ligand) system is also severely disrupted during the osteogenesis process while coupling with angiogenesis, both of which eventually lead to abnormal endochondral bone formation in TD chickens. Thus, the process of vascular formation in endochondral bone appears to initiate the pathological changes in TD, and improvement of this process during coupling with osteogenesis may be a potential therapeutic approach to treat this intractable disease

Venous thromboembolism in immobilized patients with dementia. Findings from the RIETE registry.

BACKGROUND: The natural history of venous thromboembolism (VTE) in patients with dementia has not been thoroughly studied. METHODS: We used the RIETE Registry data to assess the clinical characteristics, treatment strategies and outcome during the first 3 months after acute VTE in all immobilized patients with dementia. RESULTS: As of August 2011, 37988 patients had been enrolled, of whom 1316 (3.5%) had dementia. Most patients in both subgroups were initially treated with low-molecular-weight heparin (LMWH). Then, 48% of patients with dementia and 25% of those without dementia received LMWH as long-term therapy. During the first 3 months of anticoagulant therapy, patients with dementia had a higher incidence of fatal pulmonary embolism (PE): 4.0% vs. 1.2% (odds ratio: 3.3; 95% CI: 2.5-4.4) and fatal bleeding: 1.4% vs. 0.5% (odds ratio: 2.9; 95% CI: 1.8-4.6) than those without dementia. In demented patients initially presenting with PE, the incidence of fatal PE during the first week outweighed that of fatal bleeding (42 vs. 4 deaths), but from Day 8, the incidence of fatal PE was similar to the incidence of fatal bleeding. In patients initially presenting with deep vein thrombosis (DVT), there were 4 fatal PE and 8 fatal bleeding events. CONCLUSIONS: VTE patients with dementia had a high incidence of fatal PE and fatal bleeding. In those initially presenting with PE, the risk of dying of PE far outweighed that of fatal bleeding. In patients presenting with DVT alone, the risk of fatal PE was lower than that of fatal bleeding

Long-term therapy with low-molecular-weight heparin in cancer patients with venous thromboembolism

Long-term therapy with low-molecular-weight heparin (LMWH) is the treatment of choice for cancer patients with venous thromboembolism (VTE). However, the ideal doses of LMWH have not been thoroughly studied. We used the RIETE Registry data to assess the influence of the daily LMWH dosage on outcome during the first three months after VTE. We used propensity score-matching to compare patients who received <150 vs. those receiving 65150 UI/kg/day LMWH. Up to July 2010, 3,222 cancer patients with VTE received long-term therapy with fixed doses of LMWH. Of these, 1,472 (46%) received <150 IU/kg/day (mean, 112 \ub1 28), and 1,750 received 65150 IU/kg/day (mean, 184 \ub1 32). Results of the propensity score matching involved 1269 matched pairs. During follow-up, the incidence of pulmonary embolism (PE) recurrences was similar (1.2% vs. 1.9%), but patients receiving <150 IU/kg/day LMWH had a lower incidence of fatal PE than those treated with 65150 IU/kg/day (0.2% vs. 1.0%; p=0.004). Multivariate analysis confirmed that patients receiving <150 IU/kg/day LMWH had a lower risk for fatal PE (odds ratio [OR]: 0.2; 95% confidence interval [CI]: 0.06-0.8) and for major bleeding (OR: 0.6; 95% CI: 0.3-1.0) than those treated with 65150 IU/kg/day. In real life, one in every two cancer patients with VTE received lower doses of LMWH than those used in randomised trials, with large variations from patient to patient. Unexpectedly, patients treated with <150 IU/kg/day LMWH had fewer fatal PE cases and fewer major bleeding events than those receiving 65150 IU/kg/day LMWH. This finding, however, should be validated in prospective clinical trials