Extracellular matrix hydrogel therapies: In vivo applications and development

Spang, Martin T.; Christman, Karen L.

doi:10.1016/j.actbio.2017.12.019

Cited by 246 publications

(212 citation statements)

References 174 publications

(267 reference statements)

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“…ECM hydrogels may also be applicable for 3D culturing, 3D bioprinting and in vivo tissue regeneration [25]. These can be in a donor-independent fashion and over a species barrier while SVF which can be used only as an allogeneic transplant otherwise immunological rejection would occur.…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue-derived ECM hydrogels and their use as 3D culture scaffold

Getova

Dongen

Brouwer

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Adipose tissue has the therapeutic capacity in the form of a fat graft, for example, for treatment of irradiation-induced scars and difficult to heal dermal wounds. For large-scale clinical application, an offthe-shelf product is warranted. In recent years, ECM-derived hydrogels are postulated to harbour therapeutic capacity and might even replicate the beneficial effects of adipose tissue. In normal homeostasis, the natural ECM acts as a deposit of growth factors, that releases them over time. In the healing of lesions, this might promote cell accumulation and proliferation which in turn stimulates angiogenesis and repair. The decellularization of tissue and the generation of hydrogels may leave cytotoxic traces. Therefore, our research assessed the cytotoxic effect of human adipose tissue-derived ECM hydrogels on connective tissue cells i.e. fibroblasts. The results showed no cytotoxicity, meaning the hydrogels caused no cell death. Cell migration and survival were observed when cultured in ECM hydrogels and followed for 7 days. Cell survival in the hydrogel was confirmed with CFDA staining and also cells showed the ability to penetrate and migrate throughout the gel. We conclude that ECM hydrogels are promising to use as innovative therapy for wound healing. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Adipose tissue-derived ECM hydrogels and their use as 3D culture scaffold

Getova

Dongen

Brouwer

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Thus, the direct combination of scaffolds functionalized with simplified ECM proteins is widely studied as a promising approach for a broad range of biomedical applications. Biomaterials functionalized with ECM‐derived proteins were demonstrated to significantly affect cell behavior . However, direct functionalization of a surface with an active molecule (i.e.…”

Section: Introductionmentioning

confidence: 99%

“…Biomaterials functionalized with ECM-derived proteins were demonstrated to significantly affect cell behavior. 5 However, direct functionalization of a surface with an active molecule (i.e. a protein) could result in random non-specific adsorption, loss of functionality or triggering of undesired reactions.…”

Section: Introductionmentioning

confidence: 99%

Surface modification of chitosan films with a fibronectin fragment–DNA aptamer complex to enhance osteoblastic cell activity: A mass spectrometry approach probing evidence on protein behavior

Saccani

Parisi

Bergonzi

et al. 2019

Rapid Comm Mass Spectrometry

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Rationale Protein dynamics are fundamental for biological activity. Direct surface functionalization with these biomolecules often creates regions presenting non‐homogeneous and altered protein functionality. Aptamers have been shown to be an effective method to enhance the biocompatibility of biomaterials by acting as docking points for biomolecules capable of improving cell responses and the colonization/proliferation processes. Here mass spectrometry (MS) was successfully applied as an analytical approach to study the interactions between a fibronectin fragment (FN) and anti‐fibronectin aptamers in solution and on a chitosan film. Methods A 30 kDa N‐terminal fibronectin fragment, a ssDNA anti‐fibronectin 40 nucleotide long aptamer and chitosan 95/50 (degree of deacetylation 92.6–97.5%; molecular weight 80–220 kDa) were used. First, the dynamics of the FN in aqueous solution, in the presence or absence of anti‐FN‐specific DNA aptamers, were described. Thus, the same study was carried out on 2% (w/w) chitosan‐based films, functionalized with FN alone or through aptamers as selective spacers. Results Amide hydrogen/deuterium exchange mass spectrometry (HDX‐MS) analysis identified the SYRIGDTWSKKDNRGNL and YRVGDTYERPKDSMI, YVVGETWEKPYQGWMM and WERTYLGNAL fragments as presumably involved in the interaction of FN with aptamers. MS findings indicated the improved functionality of FN on chitosan when aptamers were used as selective spacer, and this may explain why cells preferentially attached to aptamer‐bound FN rather than on chitosan‐FN films. Conclusions Aptamers did not affect the amount of adsorbed FN, but influenced its conformation enhancing its biological activity toward adhesion and growth of osteoblasts. HDX‐MS data allowed the identification of the FN/aptamer interaction regions. Differences in FN flexibility on the chitosan film in the presence or absence of the aptamer were established providing insights at the molecular level to better understand the protein biological functionality on cell proliferation.

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“…Therefore, researchers have capitalized on the cell instructive and regenerative potential of these naturally bioactive materials to develop matrix-derived scaffolds for regenerative applications, examples of which include repair of bone [9,10], cartilage [11], brain and spinal cord [12,13], pancreas [14] and a host of other tissues [15].…”

Section: Introductionmentioning

confidence: 99%

BoneMA – Synthesis and Characterization of a Methacrylated Bone-derived Hydrogel for Bioprinting of Vascularized Tissues

Athirasala

Tahayeri

et al. 2020

Preprint

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† These authors contributed equally to this work. AbstractIt has long been proposed that recapitulating the extracellular matrix (ECM) of native human tissues in the laboratory may enhance the regenerative capacity of engineered scaffolds in-vivo.Organ-and tissue-derived decellularized ECM biomaterials have been widely used for tissue repair, especially due to their intrinsic biochemical cues that can facilitate repair and regeneration. The main purpose of this study was to synthesize a new photocrosslinkable human bone-derived ECM hydrogel for bioprinting of vascularized scaffolds. To that end, we demineralized and decellularized human bone fragments to obtain a bone matrix, which was further processed and functionalized with methacrylate groups to form a photocrosslinkable methacrylate bone ECM hydrogel -BoneMA. The mechanical properties of BoneMA were tunable, with the elastic modulus increasing as a function of photocrosslinking time, while still retaining the nanoscale features of the polymer networks. The intrinsic cell-compatibility of the bone matrix ensured the synthesis of a highly cytocompatible hydrogel. The bioprinted BoneMA scaffolds supported vascularization of endothelial cells and within a day led to the formation of interconnected vascular networks. We propose that such a quick vascular network formation was due to the host of pro-angiogenic biomolecules present in the bone ECM matrix.Further, we also demonstrate the bioprintability of BoneMA in microdimensions as injectable ECM-based building blocks for microscale tissue engineering in a minimally invasive manner.We conclude that BoneMA may be a useful hydrogel system for tissue engineering and regenerative medicine. hDPSCs encapsulated in GelMA hydrogels crosslinked for 15, 30, and 45 secs and stained for live (blue) and dead (green) cells at 1, 3 and 7 day time points showed a high degree of viability across all conditions and time points. Scale bar -400 μm. Figure S4. Both positive and negative features ranging from 500 -1000 μm in width were printed using BoneMA after a crosslinking time of 45 seconds. The resolution for the negative was better than positive for the 500 μm square print. Supplementary Figure S5. Shear storage modulus of BoneMA and GelMA. A) The shear storage modulus of BoneMA increased during the first 100 seconds of crosslinking. During this period, the shear storage modulus reached approximately 500 Pa, and beyond 100 seconds, the value reached approximately 750 Pa, where the curve remained a constant after 150 seconds. B) GelMA had a sharp increase in storage modulus during the first 50 seconds, and the value reached approximately 2 kPa. The curve hit a constant at 125 seconds when the shear storage modulus reached a value of approximately 2.5 kPa. Supplementary

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Extracellular matrix hydrogel therapies: In vivo applications and development

Cited by 246 publications

References 174 publications

Adipose tissue-derived ECM hydrogels and their use as 3D culture scaffold

Adipose tissue-derived ECM hydrogels and their use as 3D culture scaffold

Surface modification of chitosan films with a fibronectin fragment–DNA aptamer complex to enhance osteoblastic cell activity: A mass spectrometry approach probing evidence on protein behavior

BoneMA – Synthesis and Characterization of a Methacrylated Bone-derived Hydrogel for Bioprinting of Vascularized Tissues

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