Regulation of tissue ingrowth into proteolytically degradable hydrogels

Goetsch, K.P.; Bracher, Mona; Bezuidenhout, Deon; Zilla, Peter; Davies, Neil

doi:10.1016/j.actbio.2015.06.009

Cited by 17 publications

(23 citation statements)

References 43 publications

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“…For none of these materials do we have an answer to two of the critical questions asked at the beginning: (1) as scaffolds, do they allow transmural endothelialisation or alternatively facilitate true fall-out endothelialisation and (2) given the absence of trans-anastomotic neointimal outgrowth in man: is scaffold degradation (eg., by blood borne inflammatory cells) balanced against neo-tissue formation to prevent a premature structure-loss in patients? The same questions need to be asked with regards to the effect of incorporated/grafted bioactive molecules such as VEGF (361,366,367,409), NO (364), TGF-b (410), SFD-1 (411), and many others (368,412) not to mention the various ingrowth gels whether they are from natural proteins (388,407,413,414) or fully synthetic (415); functionalised, (416)(417)(418)(419)(420)(421)(422) and/or potentially cell selective (423). For gels, however, an important second purpose may emerge as "space-holders" further facilitating transmural endothelialisation.…”

Section: Synthetic (Functionalised) Scaffoldsmentioning

confidence: 99%

Progressive Reinvention or Destination Lost? Half a Century of Cardiovascular Tissue Engineering

Zilla

Deutsch

Bezuidenhout

et al. 2020

Front. Cardiovasc. Med.

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Section: Synthetic (Functionalised) Scaffoldsmentioning

confidence: 99%

Progressive Reinvention or Destination Lost? Half a Century of Cardiovascular Tissue Engineering

Zilla

Deutsch

Bezuidenhout

et al. 2020

Front. Cardiovasc. Med.

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“…40 These hydrogels have also been utilized as microcarriers for controlled release and drug delivery. 1,30,31 While many studies have utilized a peptide sequence derived from collagen type I, which degrades in response to generic pan-MMPs (e.g., 34 ), this platform can be further tuned to target degradation by a specific MMP or cell type 19 thus controlling when and what degrades the hydrogel. 9 For example, hydrogels sensitive to MMP-13, which is up-regulated during bone injury and secreted by MSCs, have been shown to support osteogenic differentiation of mesenchymal stem cells in vitro 23,27 and regenerate bone-like tissue in vivo .…”

Section: Introductionmentioning

confidence: 99%

The In Vitro and In Vivo Response to MMP-Sensitive Poly(Ethylene Glycol) Hydrogels

Amer

Bryant

2016

Ann Biomed Eng

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Enzyme-sensitive hydrogels are a promising class of materials for cell encapsulation and tissue engineering because their ability to be degraded by cell-secreted factors. However, it is well known that nearly all synthetic biomaterials elicit a foreign body response upon implantation. Therefore, this study aimed to evaluate the in vitro and in vivo response to an enzyme-sensitive hydrogel. Hydrogels were formed from poly(ethylene glycol) with the peptide crosslinker, C-VPLS↓LYSG-C, which is susceptible to matrix metalloproteinases 2 and 9. We evaluated the hydrogel by exogenously delivered enzymes, encapsulated mesenchymal stem cells as a tissue engineering relevant cell type, and by macrophage-secreted factors in vitro and for the foreign body response through macrophage attachment in vitro and in a subcutaneous mouse model. These hydrogels rapidly degraded upon exposure to exogenous MMP-2 and to lesser degree with MMP-9. Encapsulated mesenchymal stem cells were capable of degrading the hydrogels via matrix metalloproteinases. Inflammatory macrophages were confirmed to attach to the hydrogels, but were not capable of rapidly degrading the hydrogels. In vivo, these hydrogels remained intact after 4 weeks and exhibited a classic foreign body response with inflammatory cells at the hydrogel surface and a fibrous capsule. In summary, these findings suggest that while this MMP-2/9 sensitive hydrogel is readily degraded in vitro, it does not undergo rapid degradation by the foreign body response. Thus, the long term stability of these hydrogels in vivo coupled with the ability for encapsulated cells to degrade the hydrogel makes them promising materials for tissue engineering.

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“…Hydrogel crosslinks can be engineered to exhibit properties which makes it possible for a hydrogel to degrade with time. In this regard, hydrogel crosslinks can be designed so they degrade by hydrolysis [78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95], or by enzymatic action [64,69,73,75,76,96,97,98,99,100,101,102,103,104,105]. An examination of the scientific literature shows how versatile hydrogels can be in many biomedical applications.…”

Section: Encapsulation Within Hydrogels For Medical Applicationsmentioning

confidence: 99%

Encapsulation of Biological Agents in Hydrogels for Therapeutic Applications

Pérez-Luna

González-Reynoso

2018

Gels

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Hydrogels are materials specially suited for encapsulation of biological elements. Their large water content provides an environment compatible with most biological molecules. Their crosslinked nature also provides an ideal material for the protection of encapsulated biological elements against degradation and/or immune recognition. This makes them attractive not only for controlled drug delivery of proteins, but they can also be used to encapsulate cells that can have therapeutic applications. Thus, hydrogels can be used to create systems that will deliver required therapies in a controlled manner by either encapsulation of proteins or even cells that produce molecules that will be released from these systems. Here, an overview of hydrogel encapsulation strategies of biological elements ranging from molecules to cells is discussed, with special emphasis on therapeutic applications.

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Regulation of tissue ingrowth into proteolytically degradable hydrogels

Cited by 17 publications

References 43 publications

Progressive Reinvention or Destination Lost? Half a Century of Cardiovascular Tissue Engineering

Progressive Reinvention or Destination Lost? Half a Century of Cardiovascular Tissue Engineering

The In Vitro and In Vivo Response to MMP-Sensitive Poly(Ethylene Glycol) Hydrogels

Encapsulation of Biological Agents in Hydrogels for Therapeutic Applications

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