Transforming Growth Factor Beta 1 Augments Calvarial Defect Healing and Promotes Suture Regeneration

Shakir, Sameer; MacIsaac, Zoe M.; Naran, Sanjay; Smith, Darren M.; Bykowski, Michael R.; Cray, James J.; Craft, Timothy K.; Wang, Dan; Weiss, Lee E.; Campbell, Phil G.; Mooney, Mark P.; Losee, Joseph E.; Cooper, Gregory M.

doi:10.1089/ten.tea.2014.0189

Cited by 24 publications

(22 citation statements)

References 69 publications

(64 reference statements)

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“…47 Accordingly, several studies suggest positive effects of TGFb when used for bone repair. [48][49][50][51] PDGF-AB and PDGF-BB were other GFs found in supernatants from PRPgels in this study. PDGFs are known to promote the proliferation of bone cells and influence osteoblastic mitogenesis.…”

Section: Discussionsupporting

confidence: 56%

AnIn VitroInvestigation of Platelet-Rich Plasma-Gel as a Cell and Growth Factor Delivery Vehicle for Tissue Engineering

Jalowiec

D’Este

Bara

et al. 2016

Tissue Engineering Part C: Methods

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Platelet-rich plasma (PRP) has been used for different applications in human and veterinary medicine. Many studies have shown promising therapeutic effects of PRP; however, there are still many controversies regarding its composition, properties, and clinical efficacy. The aim of this study was to evaluate the influence of different platelet concentrations on the rheological properties and growth factor (GF) release profile of PRP-gels. In addition, the viability of incorporated bone marrow-derived human mesenchymal stem cells (MSCs) was investigated. PRP (containing 1000 × 10(3), 2000 × 10(3), and 10,000 × 10(3) platelets/μL) was prepared from human platelet concentrates. Platelet activation and gelification were achieved by addition of human thrombin. Viscoelastic properties of PRP-gels were evaluated by rheological studies. The release of GFs and inflammatory proteins was measured using a membrane-based protein array and enzyme-linked immunosorbent assay. MSC viability and proliferation in PRP-gels were assessed over 7 days by cell viability staining. Cell proliferation was examined using DNA quantification. Regardless of the platelet content, all tested PRP-gels showed effective cross-linking. A positive correlation between protein release and the platelet concentration was observed at all time points. Among the detected proteins, the chemokine CCL5 was the most abundant. The greatest release appeared within the first 4 h after gelification. MSCs could be successfully cultured in PRP-gels over 7 days, with the highest cell viability and DNA content found in PRP-gels with 1000 × 10(3) platelets/μL. The results of this study suggest that PRP-gels represent a suitable carrier for both cell and GF delivery for tissue engineering. Notably, a platelet concentration of 1000 × 10(3) platelets/μL appeared to provide the most favorable environment for MSCs. Thus, the platelet concentration is an important consideration for the clinical application of PRP-gels.

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Section: Discussionsupporting

confidence: 56%

AnIn VitroInvestigation of Platelet-Rich Plasma-Gel as a Cell and Growth Factor Delivery Vehicle for Tissue Engineering

Jalowiec

D’Este

Bara

et al. 2016

Tissue Engineering Part C: Methods

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“…The use of recombinant ligand to promote tissue regeneration might not be limited to TGFβ3. A recent study comparing the effect of TGFβ1 and BMP2 on calvarial defect healing and suture regeneration in rabbits, suggests TGFβ1 to be a superior factor in this particular setting, by promoting bone healing via the native intramembranous ossification pathway [ 171 ].…”

Section: Tgfβ Signalling Targeting In Wound Healing and Tissue Regmentioning

confidence: 99%

Signalling by Transforming Growth Factor Beta Isoforms in Wound Healing and Tissue Regeneration

Gilbert

Vickaryous

Viloria-Petit

2016

JDB

127

107

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Transforming growth factor beta (TGFβ) signalling is essential for wound healing, including both non-specific scar formation and tissue-specific regeneration. Specific TGFβ isoforms and downstream mediators of canonical and non-canonical signalling play different roles in each of these processes. Here we review the role of TGFβ signalling during tissue repair, with a particular focus on the prototypic isoforms TGFβ1, TGFβ2, and TGFβ3. We begin by introducing TGFβ signalling and then discuss the role of these growth factors and their key downstream signalling mediators in determining the balance between scar formation and tissue regeneration. Next we discuss examples of the pleiotropic roles of TGFβ ligands during cutaneous wound healing and blastema-mediated regeneration, and how inhibition of the canonical signalling pathway (using small molecule inhibitors) blocks regeneration. Finally, we review various TGFβ-targeting therapeutic strategies that hold promise for enhancing tissue repair.

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“…Uniform patterns of murine CTLA4/Fc bioink (200 mg/mL) were produced in our laboratory and printed onto 200-mm thick, 5 3 5 mm pieces of ADM (Synthes, West Chester, PA) using our inkjet-based biopatterning system (9,10,14). The printed bioink absorbs into the open-pore structure of the dermal surface and binds within the matrix to produce immobilized 3-D patterns that persist for sufficient periods of time needed to elicit the desired biological control (9).…”

Section: Creation Of Biopatterned Murine Ctla4/fc Microenvironment Inmentioning

confidence: 99%

Biopatterned CTLA4/Fc Matrices Facilitate Local Immunomodulation, Engraftment, and Glucose Homeostasis After Pancreatic Islet Transplantation

et al. 2016

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Pancreatic islet transplantation (PIT) represents a potential therapy to circumvent the need for exogenous insulin in type 1 diabetes. However, PIT remains limited by lack of donor islets and the need for long-term multidrug immunosuppression to prevent alloimmune islet rejection. Our goal was to evaluate a local immunoregulatory strategy that sustains islet allograft survival and restores glucose homeostasis in the absence of systemic immunosuppression. Nanogram quantities of murine CTLA4/Fc fusion protein were controllably delivered within human acellular dermal matrix scaffolds using an inkjet-based biopatterning technology and cotransplanted with allogeneic islets under the renal capsule to create an immunoregulatory microenvironment around the islet allograft. We achieved long-term engraftment of small loads of allogeneic islet cells with 40% of MHC-mismatched mouse recipients maintaining sustained normoglycemia following pancreatic β-cell ablation by streptozotocin. Biopatterned CTLA4/Fc local therapy was associated with expansion of Foxp3 regulatory T cells and shifts in cytokine production and gene expression from proinflammatory to regulatory profiles, thus substantially benefiting islet allografts survival and function. This study is a new paradigm for targeted therapies in PIT that demonstrates the favorable effects of immune alterations in the transplant milieu and suggests a unique strategy for minimizing systemic immunosuppression and promoting islet allograft survival.

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Transforming Growth Factor Beta 1 Augments Calvarial Defect Healing and Promotes Suture Regeneration

Cited by 24 publications

References 69 publications

AnIn VitroInvestigation of Platelet-Rich Plasma-Gel as a Cell and Growth Factor Delivery Vehicle for Tissue Engineering

AnIn VitroInvestigation of Platelet-Rich Plasma-Gel as a Cell and Growth Factor Delivery Vehicle for Tissue Engineering

Signalling by Transforming Growth Factor Beta Isoforms in Wound Healing and Tissue Regeneration

Biopatterned CTLA4/Fc Matrices Facilitate Local Immunomodulation, Engraftment, and Glucose Homeostasis After Pancreatic Islet Transplantation

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