TY  - JOUR
A1  - Sarem, Melika
A1  - Arya, Neha
A1  - Heizmann, Miriam
A1  - Neffe, Axel T.
A1  - Barbero, Andrea
A1  - Gebauer, Tim P.
A1  - Martin, Ivan
A1  - Lendlein, Andreas
A1  - Shastri, V. Prasad
T1  - Interplay between stiffness and degradation of architectured gelatin hydrogels leads to differential modulation of chondrogenesis in vitro and in vivo
JF  - Acta biomaterialia
N2  - The limited capacity of cartilage to heal large lesions through endogenous mechanisms has led to extensive effort to develop materials to facilitate chondrogenesis. Although physical-chemical properties of biomaterials have been shown to impact in vitro chondrogenesis, whether these findings are translatable in vivo is subject of debate. Herein, architectured 3D hydrogel scaffolds (ArcGel) (produced by crosslinking gelatin with ethyl lysine diisocyanate (LDI)) were used as a model system to investigate the interplay between scaffold mechanical properties and degradation on matrix deposition by human articular chondrocytes (HAC) from healthy donors in vitro and in vivo. Using ArcGel scaffolds of different tensile and shear modulus, and degradation behavior; in this study, we compared the fate of ex vivo engineeredArcGels-chondrocytes constructs, i.e. the traditional tissue engineering approach, with the de novo formation of cartilaginous tissue in HAC laden ArcGels in an ectopic nude mouse model. While the softer and fast degrading ArcGel (LNCO3) was more efficient at promoting chondrogenic differentiation in vitro, upon ectopic implantation, the stiffer and slow degrading ArcGel (LNCO8) was superior in maintaining chondrogenic phenotype in HAC and retention of cartilaginous matrix. Furthermore, surprisingly the de novo formation of cartilage tissue was promoted only in LNCO8. Since HAC cultured for only three days in the LNCO8 environment showed upregulation of hypoxia-associated genes, this suggests a potential role for hypoxia in the observed in vivo outcomes. In summary, this study sheds light on how immediate environment (in vivo versus in vitro) can significantly impact the outcomes of cell-laden biomaterials. Statement of Significance In this study, 3D architectured hydrogels (ArcGels) with different mechanical and biodegradation properties were investigated for their potential to promote formation of cartilaginous matrix by human articular chondrocytes in vitro and in vivo. Two paradigms were explored (i) ex vivo engineering followed by in vivo implantation in ectopic site of nude mice and (ii) short in vitro culture (3 days) followed by implantation to induce de novo cartilage formation. Softer and fast degrading ArcGel were better at promoting chondrogenesis in vitro, while stiffer and slow degrading ArcGel were strikingly superior in both maintaining chondrogenesis in vivo and inducing de novo formation of cartilage. Our findings highlight the importance of the interplay between scaffold mechanics and degradation in chondrogenesis.
KW  - Cartilage repair
KW  - Scaffold stiffness
KW  - Scaffold contraction
KW  - Scaffold degradation
KW  - Matrix metalloproteinase
KW  - Hypoxia
Y1  - 2018
U6  - https://doi.org/10.1016/j.actbio.2018.01.025
SN  - 1742-7061
SN  - 1878-7568
VL  - 69
SP  - 83
EP  - 94
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Licausi, Francesco
A1  - Giorgi, Federico Manuel
A1  - Schmaelzlin, Elmar
A1  - Usadel, Björn
A1  - Perata, Pierdomenico
A1  - van Dongen, Joost Thomas
A1  - Geigenberger, Peter
T1  - HRE-Type Genes are regulated by Growth-Related Changes in internal Oxygen Concentrations During the normal development of Potato (Solanum tuberosum) Tubers
JF  - Plant & cell physiology
N2  - The occurrence of hypoxic conditions in plants not only represents a stress condition but is also associated with the normal development and growth of many organs, leading to adaptive changes in metabolism and growth to prevent internal anoxia. Internal oxygen concentrations decrease inside growing potato tubers, due to their active metabolism and increased resistance to gas diffusion as tubers grow. In the present work, we identified three hypoxia-responsive ERF (StHRE) genes whose expression is regulated by the gradual decrease in oxygen tensions that occur when potato tubers grow larger. Increasing the external oxygen concentration counteracted the modification of StHRE expression during tuber growth, supporting the idea that the actual oxygen levels inside the organs, rather than development itself, are responsible for the regulation of StHRE genes. We identified several sugar metabolism-related genes co-regulated with StHRE genes during tuber development and possibly involved in starch accumulation. All together, our data suggest a possible role for low oxygen in the regulation of sugar metabolism in the potato tuber, similar to what happens in storage tissues during seed development.
KW  - Co-expression
KW  - ERF
KW  - Hypoxia
KW  - Potato
KW  - Solanum tuberosum
KW  - Tuber
Y1  - 2011
U6  - https://doi.org/10.1093/pcp/pcr128
SN  - 0032-0781
VL  - 52
IS  - 11
SP  - 1957
EP  - 1972
PB  - Oxford Univ. Press
CY  - Oxford
ER  -