Engineering the Regenerative Microenvironment with Biomaterials

Rice, Jeffrey J.; Martino, Mikaël M.; Laporte, Laura De; Tortelli, Federico; Briquez, Priscilla S.; Hubbell, Jeffrey A.

doi:10.1002/adhm.201200197

Cited by 355 publications

(316 citation statements)

References 244 publications

(281 reference statements)

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“…Clinically available fibrin is widely used as a sealant and has the potential for use as an efficient GF-delivery system for multiple purposes (29). Of special interest, we show here that an impressive number of GFs strongly bind this material.…”

Section: Discussionmentioning

confidence: 60%

“…The substitution of fibrin with a synthetic matrix would have numerous benefits, however. The tailorability of synthetic materials allows greater control of cell-matrix interactions, such as the matrix degradation rate and matrix stiffness, both of which are critical in driving tissue repair or regeneration (29). Thus, this flexibility can fill unmet needs in regenerative medicine by providing a specific and more controlled environment.…”

Section: Discussionmentioning

confidence: 99%

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Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix

Martino

Briquez

Ranga

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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417

366

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By binding growth factors (GFs), the ECM tightly regulates their activity. We recently reported that the heparin-binding domain II of fibronectin acts as a promiscuous high-affinity GF-binding domain. Here we hypothesized that fibrin, the provisional ECM during tissue repair, also could be highly promiscuous in its GF-binding capacity. Using multiple affinity-based assays, we found that fibrin(ogen) and its heparin-binding domain bind several GFs from the PDGF/VEGF and FGF families and some GFs from the TGF-β and neurotrophin families. Overall, we identified 15 unique binding interactions. The GF binding ability of fibrinogen caused prolonged retention of many of the identified GFs within fibrin. Thus, based on the promiscuous and high-affinity interactions in fibrin, GF binding may be one of fibrin’s main physiological functions, and these interactions may potentially play an important and ubiquitous role during tissue repair. To prove this role in a gain-of-function model, we incorporated the heparin-binding domain of fibrin into a synthetic fibrin-mimetic matrix. In vivo, the multifunctional synthetic matrix could fully mimic the effect of fibrin in a diabetic mouse model of impaired wound healing, demonstrating the benefits of generating a hybrid biomaterial consisting of a synthetic polymeric scaffold and recombinant bioactive ECM domains. The reproduction of GF–ECM interactions with a fibrin-mimetic matrix could be clinically useful, and has the significant benefit of a more straightforward regulatory path associated with chemical synthesis rather than human sourcing.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix

Martino

Briquez

Ranga

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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417

366

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“…Covalent bonding of growth factors to hydrogel matrix provides a more prolonged release profile, and the conjugated growth factors have more slowly degraded and internalized features. 48,49 Conjugation of bFGF to AC-RYL-PEG-SCM was confirmed via Western blot (Fig. 9A).…”

Section: Effects Of Bfgf Conjugation In Hydrogel Matrices On Msc Diffmentioning

confidence: 78%

“…Immobilization of growth factors would enable prolonged functional signaling and controlled release profile. 48 PEGylated growth factors were proved to maintain their biological activity after chemical coupling and to promote cell-cell contact formation. 49,51,75 The conjugated bFGF not only further promoted the fibroblastic differentiation of HAVIC and ADMSC but also significantly upregulated vimentin expression in BMMSC, which was not achieved by soluble bFGF.…”

mentioning

confidence: 99%

Comparison of Mesenchymal Stem Cell Source Differentiation Toward Human Pediatric Aortic Valve Interstitial Cells within 3D Engineered Matrices

Duan

Hockaday

Das

et al. 2015

Tissue Engineering Part C: Methods

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“…4,5 A particular interest has been given to growth factors, which are key signaling molecules regulating tissue repair and regeneration. 6,7 However, although a number of growth factors involved in skin repair have been identified, their translation to the clinic has been very limited, 8,9 additionally facing issues related to safety and cost-effectiveness. 10 These problems derive most likely from the fact that the growth factors are used at vastly supra-physiological levels without appropriate delivery systems.…”

Section: Scope and Significancementioning

confidence: 99%

Extracellular Matrix-Inspired Growth Factor Delivery Systems for Skin Wound Healing

Briquez

Hubbell

Martino

2015

Advances in Wound Care

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200

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Significance: Growth factors are very promising molecules for the treatment of skin wounds. However, their translation to clinical use has been seriously limited, facing issues related to safety and cost-effectiveness. These problems may derive from the fact that growth factors are used at vastly supraphysiological levels without optimized delivery systems. Recent Advances: The extracellular matrix (ECM) plays a fundamental role in coordinating growth factor signaling. Therefore, understanding the mechanisms by which the ECM modulates growth factor activity is key for designing efficient growth factor-based therapies. Recently, several growth factorbinding domains have been discovered within various ECM proteins, and growth factor delivery systems integrating these ECM growth factor-binding domains showed promising results in animal models of skin wound healing. Moreover, a novel strategy consisting of engineering growth factors to target endogenous ECM could substantially enhance their efficacy, even when used at low doses. Critical Issues: Optimal delivery of growth factors often requires complex engineered biomaterial matrices, which can face regulatory issues for clinical translation. To simplify delivery systems and render strategies more applicable, growth factors can be engineered to optimally function with clinically approved biomaterials or with endogenous ECM present at the delivery site. Future Directions: Further development and clinical trials will reveal whether growth factor-based therapies can be used as main therapeutic approaches for skin wound healing. The future impact of these therapies will depend on our capacity to deliver growth factors more precisely, to improve efficacy, safety, and cost-effectiveness.

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Engineering the Regenerative Microenvironment with Biomaterials

Cited by 355 publications

References 244 publications

Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix

Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix

Comparison of Mesenchymal Stem Cell Source Differentiation Toward Human Pediatric Aortic Valve Interstitial Cells within 3D Engineered Matrices

Extracellular Matrix-Inspired Growth Factor Delivery Systems for Skin Wound Healing

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