Collagen — Emerging collagen based therapies hit the patient

Neel, Ensanya A. Abou; Bozec, Laurent; Knowles, Jonathan C.; Syed, Omaer; Mudera, Vivek; Day, Richard M.; Hyun, Jung Keun

doi:10.1016/j.addr.2012.08.010

Cited by 258 publications

(128 citation statements)

References 349 publications

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“…10,11 Although collagen gels support cell adhesion and growth and are enzymatically degraded into cell-tolerated products, these scaffolds lack robust control of mechanical properties, which are emerging as important in regulating gross mechanical function and defining the microniche environment of resident cells. 14−17 …”

Section: Introductionmentioning

confidence: 99%

Methacrylation Induces Rapid, Temperature-Dependent, Reversible Self-Assembly of Type-I Collagen

et al. 2014

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Type-I collagen self-assembles into a fibrillar gel at physiological temperature and pH to provide a cell-adhesive, supportive, structural network. As such, it is an attractive, popular scaffold for in vitro evaluations of cellular behavior and for tissue engineering applications. In this study, type-I collagen is modified to introduce methacrylate groups on the free amines of the lysine residues to create collagen methacrylamide (CMA). CMA retains the properties of collagen such as self-assembly, biodegradability, and natural bioactivity but is also photoactive and can be rapidly cross-linked or functionalized with acrylated molecules when irradiated with ultraviolet light in the presence of a photoinitiator. CMA also demonstrates unique temperature-dependent behavior. For natural type-I collagen, the overall structure of the fiber network remains largely static over time scales of a few hours upon heating and cooling at temperatures below its denaturation point. CMA, however, is rapidly thermoreversible and will oscillate between a liquid macromer suspension and a semisolid fibrillar hydrogel when the temperature is modulated between 10 and 37 °C. Using a series of mechanical, scattering, and spectroscopic methods, we demonstrate that structural reversibility is manifest across multiple scales from the protein topology of the triple helix up through the rheological properties of the CMA hydrogel. Electron microscopy imaging of CMA after various stages of heating and cooling shows that the canonical collagen-like D-periodic banding ultrastructure of the fibers is preserved. A rapidly thermoreversible collagen-based hydrogel is expected to have wide utility in tissue engineering and drug delivery applications as a biofunctional, biocompatible material. Thermal reversibility also makes CMA a powerful model for studying the complex process of hierarchical collagen self-assembly.

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Section: Introductionmentioning

confidence: 99%

Methacrylation Induces Rapid, Temperature-Dependent, Reversible Self-Assembly of Type-I Collagen

et al. 2014

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“…Thus, collagen is a great candidate protein to serve as a naturally derived biomaterial to facilitate the regeneration of damaged tissues. Collagen provides good cell attachment sites via integrin-binding proteins and is generally non-immunogenic among various mammalian species when implanted in vivo [19]. The ability of collagen solution to gel at a neutral pH and physiological temperature allows collagen solution to be injected to fill lesions or implant cell-seeded gel scaffolds at the injured site [20].…”

Section: Introductionmentioning

confidence: 99%

“…The ability of collagen solution to gel at a neutral pH and physiological temperature allows collagen solution to be injected to fill lesions or implant cell-seeded gel scaffolds at the injured site [20]. An acetic acid-soluble collagen containing non-helical end regions undergoes in vitro fibrillogenesis in a nucleation phase into collagen fibrils with weak interactions that are subsequently enhanced by covalent cross-linking in a rapid growth phase [19,21]. In the cell-free environment, the fibrils are formed as a highly interconnected random network or mesh of long continuous fibrils with different D-banded characteristic, length and diameter depending on the growth conditions (such as pH, temperature, buffer, ions and protein concentration), the source, type of collagen and extraction method [22,23].…”

Section: Introductionmentioning

confidence: 99%

Protocol and cell responses in three-dimensional conductive collagen gel scaffolds with conductive polymer nanofibres for tissue regeneration

2014

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It has been established that nerves and skeletal muscles respond and communicate via electrical signals. In regenerative medicine, there is current emphasis on using conductive nanomaterials to enhance electrical conduction through tissue-engineered scaffolds to increase cell differentiation and tissue regeneration. We investigated the role of chemically synthesized polyaniline (PANI) and poly(3,4-ethylenedioxythiophene) (PEDOT) conductive polymer nanofibres for conductive gels. To mimic a naturally derived extracellular matrix for cell growth, type I collagen gels were reconstituted with conductive polymer nanofibres and cells. Cell viability and proliferation of PC-12 cells and human skeletal muscle cells on these three-dimensional conductive collagen gels were evaluated in vitro. PANI and PEDOT nanofibres were found to be cytocompatible with both cell types and the best results (i.e. cell growth and gel electrical conductivity) were obtained with a low concentration (0.5 wt%) of PANI. After 7 days of culture in the conductive gels, the densities of both cell types were similar and comparable to collagen positive controls. Moreover, PC-12 cells were found to differentiate in the conductive hydrogels without the addition of nerve growth factor or electrical stimulation better than collagen control. Importantly, electrical conductivity of the three-dimensional gel scaffolds increased by more than 400% compared with control. The increased conductivity and injectability of the cell-laden collagen gels to injury sites in order to create an electrically conductive extracellular matrix makes these biomaterials very conducive for the regeneration of tissues.

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“…In this respect, extracellular matrix (ECM)-based biomaterials have attracted great interest, particularly those derived from collagens [5]. Collagens are the primary ECM components of many tissues including skin, tendon and blood vessels.…”

Section: Introductionmentioning

confidence: 99%

Modulation of inflammation and angiogenesis and changes in ECM GAG-activity via dual delivery of nucleic acids

et al. 2015

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Collagen — Emerging collagen based therapies hit the patient

Cited by 258 publications

References 349 publications

Methacrylation Induces Rapid, Temperature-Dependent, Reversible Self-Assembly of Type-I Collagen

Methacrylation Induces Rapid, Temperature-Dependent, Reversible Self-Assembly of Type-I Collagen

Protocol and cell responses in three-dimensional conductive collagen gel scaffolds with conductive polymer nanofibres for tissue regeneration

Modulation of inflammation and angiogenesis and changes in ECM GAG-activity via dual delivery of nucleic acids

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