Damage associated molecular patterns within xenogeneic biologic scaffolds and their effects on host remodeling

Daly, Kerry A.; Liu, S.; Agrawal, Vineet; Brown, Bryan N.; Johnson, Scott A.; Medberry, Christopher J.; Badylak, Stephen F.

doi:10.1016/j.biomaterials.2011.09.040

Cited by 85 publications

(71 citation statements)

References 56 publications

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“…Future modifications including the addition of angiogenic growth factors such as VEGF may improve this outcome. Although minimal immune reaction to decellularized tissues has been found (Wiles et al 2016), damage-associated molecular pattern proteins and major histocompatibility complexes I and II can evoke immune responses that can deleteriously affect implant survival (Daly et al 2012;Haykal et al 2013). The fact that we observed necrotic tissues in both cellularized and acellular dTBs suggests that the observed necrosis is not caused by the seeded xenogeneic cells alone.…”

Section: Discussionmentioning

confidence: 61%

Decellularized Tooth Bud Scaffolds for Tooth Regeneration

et al. 2017

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Whole tooth regeneration approaches currently are limited by our inability to bioengineer full-sized, living replacement teeth. Recently, decellularized organ scaffolds have shown promise for applications in regenerative medicine by providing a natural extracellular matrix environment that promotes cell attachment and tissue-specific differentiation leading to full-sized organ regeneration. We hypothesize that decellularized tooth buds (dTBs) created from unerupted porcine tooth buds (TBs) can be used to guide reseeded dental cell differentiation to form whole bioengineered teeth, thereby providing a potential off-the-shelf scaffold for whole tooth regeneration. Porcine TBs were harvested from discarded 6-mo-old pig jaws, and decellularized by successive sodium dodecyl sulfate/Triton-X cycles. Four types of replicate implants were used in this study: 1) acellular dTBs; 2) recellularized dTBs seeded with porcine dental epithelial cells, human dental pulp cells, and human umbilical vein endothelial cells (recell-dTBs); 3) dTBs seeded with bone morphogenetic protein (BMP)-2 (dTB-BMPs); and 4) freshly isolated nondecellularized natural TBs (nTBs). Replicate samples were implanted into the mandibles of host Yucatan mini-pigs and grown for 3 or 6 mo. Harvested mandibles with implanted TB constructs were fixed in formalin, decalcified, embedded in paraffin, sectioned, and analyzed via histological methods. Micro-computed tomography (CT) analysis was performed on harvested 6-mo samples prior to decalcification. All harvested constructs exhibited a high degree of cellularity. Significant production of organized dentin and enamel-like tissues was observed in dTB-recell and nTB implants, but not in dTB or dTB-BMP implants. Micro-CT analyses of 6-mo implants showed the formation of organized, bioengineered teeth of comparable size to natural teeth. To our knowledge, these results are the first to describe the potential use of dTBs for functional whole tooth regeneration.

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Section: Discussionmentioning

confidence: 61%

Decellularized Tooth Bud Scaffolds for Tooth Regeneration

et al. 2017

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“…Preclinical studies have shown a strong positive correlation between ECM bioscaffold degradation, an increased M2:M1 ratio, and constructive remodeling outcomes Brown et al 2012;Sicari et al 2012b). During the process of scaffold degradation, there is generation of bioactive cryptic peptides (Anderson et al 2008;Agrawal et al 2011a,b;Daly et al 2012) and a release of embedded GFs, cytokines, and MBVs from the normal matrix as described earlier. In contrast, chemical crosslinking of scaffolds, as it is performed with some commercially available ECM bioscaffolds (see Table 1), prevents degradation Brown et al 2009;Tierney et al 2009), results in a chronic M1-like proinflammatory response, lack of positive remodeling outcomes, and deposition of scar tissue.…”

Section: Modulation Of the Inflammatory Responsementioning

confidence: 99%

“…ECM degradation products produced during tissue remodeling, called cryptic peptides (Anderson et al 2008;Agrawal et al 2011a,b;Daly et al 2012), together with the release of the GFs retained in the ECM (Hodde et al 2001;Rieder et al 2004;Badylak 2014;Cavallo et al 2015), are believed to be responsible for many aspects of ECM-mediated bioactivity. Cryptic peptides are either created or exposed after the proteolysis of ECM components such as collagen, laminin, and fibronectin and their bioactivity is not present in the parent molecule (Anderson et al 2008;Daly et al 2012). An example is ArgGly-Asp peptide, which is part of fibronectin and collagen and, when exposed, promotes cell adhesion (Brown and Badylak 2014).…”

Section: Mechanisms Of Ecm Bioscaffold Remodelingmentioning

confidence: 99%

Biologic Scaffolds

Costa

Naranjo

Londoño

et al. 2017

Cold Spring Harb Perspect Med

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“…Although standards for decellularization have not been established by the Food and Drug Administration or United States pharmacopeia, studies have shown that the presence of cell remnants in biologic scaffold materials has pro-inflammatory and deleterious effect upon the in vivo remodeling process [117,123,124]. Decellularization criteria have been suggested and include the following: (1) The most effective methods for tissue decellularization are determined by multiple factors, including the tissue's cellularity (e.g.…”

Section: Ecm Scaffolds -The Decellularization Processmentioning

confidence: 99%