Collagen-Binding Peptidoglycans: A Biomimetic Approach to Modulate Collagen Fibrillogenesis for Tissue Engineering Applications

Paderi, John; Sistiabudi, Rizaldi; Ivanisevic, Albena; Panitch, Alyssa

doi:10.1089/ten.tea.2009.0014

Cited by 34 publications

(32 citation statements)

References 47 publications

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“…In contrast, the peptidoglycan treated wounds did not contain any of these abnormally large fibrils and had a distribution of fibril diameters more closely resembling that of uninjured skin. These results corroborate our previous in vitro studies and indicate that the synthetic peptidoglycan regulates collagen organization and prevents lateral aggregation of collagen fibrils in a manner similar to decorin [5], [12]…”

Section: Discussionsupporting

confidence: 92%

Collagen-Binding Peptidoglycans Inhibit MMP Mediated Collagen Degradation and Reduce Dermal Scarring

et al. 2011

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Scarring of the skin is a large unmet clinical problem that is of high patient concern and impact. Wound healing is complex and involves numerous pathways that are highly orchestrated, leaving the skin sealed, but with abnormal organization and composition of tissue components, namely collagen and proteoglycans, that are then remodeled over time. To improve healing and reduce or eliminate scarring, more rapid restoration of healthy tissue composition and organization offers a unique approach for development of new therapeutics. A synthetic collagen-binding peptidoglycan has been developed that inhibits matrix metalloproteinase-1 and 13 (MMP-1 and MMP-13) mediated collagen degradation. We investigated the synthetic peptidoglycan in a rat incisional model in which a single dose was delivered in a hyaluronic acid (HA) vehicle at the time of surgery prior to wound closure. The peptidoglycan treatment resulted in a significant reduction in scar tissue at 21 days as measured by histology and visual analysis. Improved collagen architecture of the treated wounds was demonstrated by increased tensile strength and transmission electron microscopy (TEM) analysis of collagen fibril diameters compared to untreated and HA controls. The peptidoglycan's mechanism of action includes masking existing collagen and inhibiting MMP-mediated collagen degradation while modulating collagen organization. The peptidoglycan can be synthesized at low cost with unique design control, and together with demonstrated preclinical efficacy in reducing scarring, warrants further investigation for dermal wound healing.

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Section: Discussionsupporting

confidence: 92%

Collagen-Binding Peptidoglycans Inhibit MMP Mediated Collagen Degradation and Reduce Dermal Scarring

et al. 2011

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“…Several groups have shown the effects of the aforementioned parameters on fibrillar size and microarchitecture of collagen matrices [26, 28-32]. Pepsin digested collagen structures are devoid of telopeptide sequences that are critical to fibril formation with recapitulation of native collagen D-periodic structure, unlike acid solubilized collagen, which still retains telopeptide sequences.…”

Section: Discussionmentioning

confidence: 99%

Collagen-based substrates with tunable strength for soft tissue engineering

et al. 2013

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Through the use of mechanical reinforcement of collagen matrices, mechanically strong and compliant 3D tissue mimetic scaffolds can be generated that act as scaffolds for soft tissue engineering. Collagen has been widely used for the development of materials for repair, augmentation or replacement of damaged or diseased tissue. Herein we describe a facile method for the layer-by-layer fabrication of robust planar collagen fiber constructs. Collagen gels cast in a phosphate buffer were dried to form dense collagen mats. Subsequent gels were layered and dried atop mats to create multilayer constructs possessing a range of tunable strengths (0.5 - 11 MPa) and stiffness (1 - 115 MPa). Depending on processing conditions and crosslinking of constructs, strain to failure ranged between 9 to 48%. Collagen mats were constructed into hernia patches that prevented hernia recurrence in Wistar rats.

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“…Since the applicability of natural decorin is associated with difficulties such as extractability, purity and cost, we have previously designed a peptidoglycan (DS-SILY) containing a collagen binding peptide (SILY) and a covalently attached dermatan sulfate (DS) GAG [12, 13]. DS-SILY is a decorin biomimetic that closely mimics natural decorin both structurally and functionally.…”

Section: Introductionmentioning

confidence: 99%

Incorporation of a decorin biomimetic enhances the mechanical properties of electrochemically aligned collagen threads

et al. 2011

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Orientational anisotropy of collagen molecules is integral for the mechanical strength of collagenrich tissues. We have previously reported a novel methodology to synthesize highly oriented electrochemically aligned collagen (ELAC) threads with mechanical properties converging upon those of native tendon. Decorin, a small leucine rich proteoglycan (SLRP), binds to fibrillar collagen and has been suggested to enhance the mechanical properties of tendon. Based on the structure of natural decorin, we have previously designed and synthesized a peptidoglycan (DS-SILY) that mimics decorin both structurally and functionally. In this study, we investigated the effect of the incorporation of DS-SILY on the mechanical properties and structural organization of ELAC threads. The results indicated that the addition of DS-SILY at a molar ratio of 30:1 (Collagen:DS-SILY) significantly enhanced the ultimate stress and ultimate strain of the ELAC threads. Furthermore, differential scanning calorimetry revealed that the addition of DS-SILY at a molar ratio of 30:1 resulted in a more thermally stable collagen structure. However, addition of DS-SILY at a higher concentration (10:1 Collagen:DS-SILY) yielded weaker threads with mechanical properties comparable to collagen control threads. Transmission emission microscopy revealed that the addition of DS-SILY at a higher concentration (10:1) resulted in pronounced aggregation of collagen fibrils. More importantly, these aggregates were not aligned along the long axis of the ELAC thereby compromising on the overall tensile properties of the material. We conclude that incorporation of an optimal amount of DS-SILY is a promising approach to synthesize mechanically competent collagen based biomaterials for tendon tissue engineering applications.

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Collagen-Binding Peptidoglycans: A Biomimetic Approach to Modulate Collagen Fibrillogenesis for Tissue Engineering Applications

Cited by 34 publications

References 47 publications

Collagen-Binding Peptidoglycans Inhibit MMP Mediated Collagen Degradation and Reduce Dermal Scarring

Collagen-Binding Peptidoglycans Inhibit MMP Mediated Collagen Degradation and Reduce Dermal Scarring

Collagen-based substrates with tunable strength for soft tissue engineering

Incorporation of a decorin biomimetic enhances the mechanical properties of electrochemically aligned collagen threads

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