Journal of Tissue Engineering and Regenerative Medicine (J TISSUE ENG REGEN M)
Current impact factor: 5.20
Impact Factor Rankings
|2016 Impact Factor ||Available summer 2017 |
|2014 / 2015 Impact Factor ||5.199 |
|2013 Impact Factor ||4.428 |
|2012 Impact Factor ||2.826 |
|2011 Impact Factor ||3.278 |
|2010 Impact Factor ||3.534 |
|2009 Impact Factor ||3.857 |
|2008 Impact Factor ||1.615 |
Impact factor over time
|5-year impact ||4.33 |
|Cited half-life ||3.40 |
|Immediacy index ||0.86 |
|Eigenfactor ||0.01 |
|Article influence ||1.03 |
|Other titles ||Journal of tissue engineering and regenerative medicine (En ligne), Journal of tissue engineering and regenerative medicine |
|ISSN ||1932-6254 |
|OCLC ||300182675 |
|Material type ||Periodical, Internet resource |
|Document type ||Internet Resource, Journal / Magazine / Newspaper |
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Publications in this journal
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ABSTRACT: This study examines the hypothesis that injectable collagen gel can be an effective carrier for recombinant human bone morphogenetic protein-2 (rhBMP-2)'s localization to the healing tendon-bone interface. In 36 mature New Zealand White rabbits, the upper long digital extensor tendon was cut and inserted into the proximal tibial bone tunnel. Then a rhBMP-2-containing collagen gel was injected into the tendon-bone tunnel interface, using a syringe. Histological and biomechanical assessments of the tendon-bone interface were conducted at 3 and 6 weeks after implantation. In vitro testing showed that the semi-viscous collagen gel at room temperature was transformed into a firm gel state at 37°C. The rhBMP-2 release profile showed that rhBMP-2 was released from the collagen gel for more than 28 days. In vivo testing showed that fibrocartilage and new bone are formed at the interface at 6 weeks after injection of rhBMP-2. On radiography, spotty calcification appeared and enthesis-like tissue was produced successfully in the tendon at 6 weeks after injection of rhBMP-2. Use of the viscous collagen gel and rhBMP-2 mixture increased the fusion rate between the bone tunnel and tissue graft. This study demonstrates that viscous collagen gel can be an effective carrier for rhBMP-2 delivery into surgical sites, and that the injectable rhBMP-2-containing collagen gel may be applied for the enhancement of tendon-bone interface healing in the future.
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ABSTRACT: Tissue Engineered Hypertrophic Cartilaginous Constructs Facilitate Early Bone Formation in Two Orthotopic Defect Models
Gráinne M Cunniffe,1,2 Amos Matsiko1,2,3, Emmet Thompson1,2,3, Fergal J O’Brien1,2,3, Daniel J Kelly,1,2
1Trinity Centre for Bioengineering, Trinity College Dublin, Ireland. 2Advanced Materials and Bioengineering Research Centre (AMBER), RCSI & TCD, Dublin, Ireland. 3Dept of Anatomy, Royal College of Surgeons in Ireland. Corresponding Author: firstname.lastname@example.org
Tissue engineering strategies based on endochondral ossification have begun to emerge, utilizing cartilaginous grafts generated using mesenchymal stem cells (MSCs) as a transient template to facilitate bone regeneration . Alginate gels have been shown to support chondrogenesis of MSCs in vitro, and by modifying the architecture of such hydrogels , can potentially be scaled-up to engineer cartilage grafts to treat large bone defects. The objective of this study was to explore the capacity of MSC-seeded alginate hydrogels, which are first primed in vitro to undergo chondrogenesis and hypertrophy, to facilitate regeneration of two distinct critically-sized orthotopic bone defects.
Materials and Methods
Fisher rat bone marrow MSCs were encapsulated in alginate gel (20x10^6/ml) using custom designed PDMS molds to generate channeled gels of appropriate dimensions (5mm height x 4mm diameter for femoral defect, 2mm height x 7mm diameter for cranial defect) for implantation into fisher rats. Constructs (n=4 per time point) were harvested after 4 and 8 weeks and analysed using microCT and histology to investigate levels of mineralization and bone deposition. In vivo studies were conducted with full ethical approval. Statistical differences in bone volume were compared using t-tests.
Macroscopic observation of the bones retrieved after 4 and 8 weeks indicate that the grafts were well integrated with the surrounding original bone in a repair callus. A significant (p<0.05) increase in bone formation (as determined by microCT analysis) was observed within the alginate treated femoral defect group vs. an empty control as early as 4 weeks, and this trend was observed for all defects at both 4 and 8 weeks. Histological analysis demonstrated the ingrowth of some vasculature into the defect as the alginate fragments degraded, and also demonstrated the formation of new bone along the surfaces of these fragments.
Fig. 1. Images showing mineralization within the femoral and cranial defect sites at 4 and 8 weeks.
Discussion and Conclusions
Taken together, these results illustrate the capacity of alginate gel to support chondrogenic differentiation of MSCs in vitro and the subsequent ability of this tissue to facilitate bone formation in two distinct in vivo models, inducing enhanced levels of mineralisation and bone formation compared to empty defect controls. Future studies would look to accelerate the degradation kinetics of the alginate in vivo to create more room for de novo bone deposition.
1. Huang JI et al. The Journal of Bone and Joint Surgery Apr;88(4),744, 2006.
2. Sheehy EJ et al., Tissue Eng & Reg Med 5(9),747, 2011.
This project was funded by the AO foundation under the large bone defect healing program
Authors have nothing to disclose.
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ABSTRACT: DOI: 10.1002/term.1931
Introduction: Extracellular Matrix (ECM) has been proposed as the ideal biologic scaffold material for tissue engineering (TE) applications . ECM-derived from articular cartilage has been used to produce scaffolds for cartilage TE [2,3]. It has been demonstrated in vitro that the capacity of such scaffolds to promote chondrogenesis of mesenchymal stem cells (MSC) is enhanced by endogenous growth factor (e.g. TGF-β3) supplementation . The objective of this study was to explore the potential of a cartilage ECM-derived scaffold to act as growth factor delivery system to promote chondrogenesis of human infrapatellar fat pad derived cells (FPSCs) in vitro and in vivo.
Materials and Methods: In vitro study - Cartilage ECM-derived scaffolds were fabricated using freeze-dried homogenized porcine cartilage. All scaffolds underwent dehydrothermal and 1-Ethyl-3-3-dimethyl aminopropyl carbodiimide (EDAC) crosslinking. TGF-β3 was soak-loaded into each scaffold. Human FPSCs (0.5 million) were seeded and maintained in vitro for 28 days as assessed as described below. In vivo study - Porcine FPSCs were expanded to P2 and seeded into scaffolds. Constructs (n=9) were incubated for 1 day, before implantation subcutaneously in nude mice and harvested after 4 weeks. Constructs were biochemically analyzed at day 28 for sulphated glycosaminoglycan (sGAG) and collagen content. Histological sections were stained for sGAG, cell nuclei and type II collagen.
Results: In vitro - TGF-β3 was released from the ECM-derived scaffold over a period of approximately 12 days in vitro. EDAC crosslinking delayed the early release of growth factor from the scaffold (Fig. 1). Comparable chondrogenesis of FPSCs was observed in ECM-derived scaffolds where TGF-β3 was soaked loaded onto the scaffold compared to where TGF-β3 was added to the media (data not shown). In vivo - While acellular scaffolds were infiltrated by host cells in vivo (Fig. 2), superior chondrogenesis was observed in scaffolds pre-seeded with human FPSCs.
Discussion and Conclusions: The results of this study demonstrate that a cartilage ECM-derived scaffold can be used as a growth factor delivery system to control the release of TGF-β3. This controlled release was found to induce robust chondrogenesis in vitro and supported the development of a cartilaginous tissue in vivo. We are currently evaluating the capacity of this construct as part of a single stage therapy for cartilage repair when combined with freshly isolated stromal cells.
References -  Badylak SF. Biomaterials 2007;  Rowland CR et al., Biomaterials 2013;  Cheng NC et al., T. Eng. Part A. 2009;  Diekman BO et al., T. Eng. Part A 2010.
Acknowledgments - European Research Council and PRTLI.
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ABSTRACT: DOI: 10.1002/term.1931
Introduction: Cell based therapies such as autologous chondrocyte implantation (ACI) can be used to repair damaged cartilage. However, obtaining sufficient numbers of functional chondrocytes is a limiting factor, particularly from severely damaged or diseased joints. We and others have demonstrated that infra-patellar fat pad derived stem cells (FPSCs) may a potential alternative cell source for cartilage repair . It has been reported that chondrons are rich in chondrogenic extracellular matrix components and furthermore that a co-culture of chondrons and bone marrow derived MSCs enhance chondrogenesis and cartilage regeneration in vivo . What remains unclear is whether chondrons and stem cells maintain this capacity in disease. The hypothesis of this study is that a co-culture of human chondrons and FPSCs isolated from osteoarthritic joints will enhance chondrogenesis, opening up the possibility of utilizing such a combination of cell types for the treatment of degenerative joint diseases.
Materials and methods: After informed consent from all patients and approval from the Mater Hospital ethics committee, chondrons and FPSC were isolated from articular cartilage obtained from OA patients undergoing surgery. Pellets (250,000 cells) were formed using 100% chondrons or FPSCs. For the co-culture groups, pellets were formed using 25:75 ratio of chondrons to FPSCs. Pellets were maintained in normoxic (N) or hypoxic (H) conditions. The experiment was also repeated using monolayer expanded chondrocytes (Passage 2) and FPSCs. All pellets were cultured for 4 weeks in a chondro-inductive medium (10 ng/ml TGF-b3). After 4 weeks, the pellets were assessed for DNA, glycosaminoglycan (GAG) and collagen content.
Results: Co-culture was found to significantly increase total sGAG and collagen synthesis in both normoxic (N) and hypoxic (H) co-culture compared to FPSC and chondron mono-culture pellets (Figure 1). Histological analysis confirmed this finding, with co-culture pellets taining more strongly for Alcian blue and Picrosirius red (Figure 1). Hypoxic co-culture was found to significantly enhance GAG and collagen accumulation compared to normoxic culture. Interestingly, a beneficial effect of co-culture was not observed with monolayer expanded chondrocytes (data not shown).
Discussion and conclusions: This study demonstrates that a co-culture of chondrons with FPSCs enhances chondrogenesis and cartilaginous extracellular matrix synthesis in cells isolated from diseased joints. Acknowledgments: Funding from a European Research Council Starter Grant (StemRepair). Disclosures: The authors have nothing to disclose.
References - 1. Liu Y, et al. Tissue Eng Part A. 18, 1531, 2012. 2. Bekkers et al., Am J Sports Med. 41, 2158, 2013.
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