Multimodal release of transforming growth factor-β1 and the BB isoform of platelet derived growth factor from PEGylated fibrin gels

Drinnan, Charles T.; Zhang, Ge; Alexander, Marc A.; Pulido, Arlynn S.; Suggs, Laura J.

doi:10.1016/j.jconrel.2010.03.026

Cited by 63 publications

(43 citation statements)

References 29 publications

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“…This biological scaffold is useful in several aspects: (1) it provides controlled release of conjugated protein factors; (2) it decreases the rate of protein clearance by the immune system; and (3) it localizes the delivery of protein factors to a particular site or tissue. 27 Recently our group used PEG-Fib to conjugate and deliver IGF-I to improve functional recovery of skeletal muscle following TK-I/R injury. 28 Zhang et al 29 successfully used PEG-Fib matrix-based delivery of SDF-1α to enhance myocardial remodeling.…”

Section: Introductionmentioning

confidence: 99%

Controlled delivery of SDF-1α and IGF-1: CXCR4⁺ cell recruitment and functional skeletal muscle recovery

et al. 2015

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Therapeutic delivery of regeneration-promoting biological factors directly to the site of injury has demonstrated its efficacy in various injury models. Several reports describe improved tissue regeneration following local injection of tissue specific growth factors, cytokines and chemokines. Evidence exists that combined cytokine/growth factor treatment is superior for optimizing tissue repair by targeting different aspects of the regeneration response. The purpose of this study was to evaluate the therapeutic potential of the controlled delivery of stromal cell-derived factor-1alpha (SDF-1α) alone or in combination with insulin-like growth factor-I (SDF-1α/IGF-I) for the treatment of tourniquet-induced ischemia/reperfusion injury (TK-I/R) of skeletal muscle. We hypothesized that SDF-1α will promote sustained stem cell recruitment to the site of muscle injury, while IGF-I will induce progenitor cell differentiation to effectively restore muscle contractile function after TK-I/R injury while concurrently reducing apoptosis. Utilizing a novel poly-ethylene glycol PEGylated fibrin gel matrix (PEG-Fib), we incorporated SDF-1α alone (PEG-Fib/SDF-1α) or in combination with IGF-I (PEG-Fib/SDF-1α/IGF-I) for controlled release at the site of acute muscle injury. Despite enhanced cell recruitment and revascularization of the regenerating muscle after SDF-1α treatment, functional analysis showed no benefit from PEG-Fib/SDF-1α therapy, while dual delivery of PEG-Fib/SDF-1α/IGF-I resulted in IGF-I-mediated improvement of maximal force recovery and SDF-1α-driven in vivo neovasculogenesis. Histological data supported functional data, as well as highlighted the important differences in the regeneration process among treatment groups. This study provides evidence that while revascularization may be necessary for maximizing muscle force recovery, without modulation of other effects of inflammation it is insufficient.

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Section: Introductionmentioning

confidence: 99%

Controlled delivery of SDF-1α and IGF-1: CXCR4⁺ cell recruitment and functional skeletal muscle recovery

et al. 2015

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“…Fibrin glue and modifications thereof have been shown to be an effective delivery medium for multipotent cells and growth factors in a number tissue engineering applications. [97][98][99][100] Platelet-enriched fibrin glue has been shown to be an effective substrate for bone-tissue engineering applications both in the presence and absence of encapsulated MSCs. 101,102 Ito et al showed an increase in bone regeneration in a canine mandibular defect using MSC/PRP/fibrin glue hybrid constructs compared to MSC/fibrin glue constructs alone after 4 and 8 weeks 103 ; however, other studies have reported no benefit to similar hybrid constructs.…”

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confidence: 99%

Uncultured Marrow Mononuclear Cells Delivered Within Fibrin Glue Hydrogels to Porous Scaffolds Enhance Bone Regeneration Within Critical-Sized Rat Cranial Defects

Kretlow

Spicer

Jansen

et al. 2010

Tissue Engineering Part A

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For bone tissue engineering, the benefits of incorporating mesenchymal stem cells (MSCs) into porous scaffolds are well established. There is, however, little consensus on the effects of or need for MSC handling ex vivo. Culture and expansion of MSCs adds length and cost, and likely increases risk associated with treatment. We evaluated the effect of using uncultured bone marrow mononuclear cells (bmMNCs) encapsulated within fibrin glue hydrogels and seeded into porous scaffolds to regenerate bone over 12 weeks in an 8-mm-diameter, criticalsized rat cranial defect. A full factorial experimental design was used to evaluate bone formation within model poly(L-lactic acid) and corraline hydroxyapatite scaffolds with or without platelet-rich plasma (PRP) and bmMNCs. Mechanical push-out testing, microcomputed tomographical analyses, and histology were performed. PRP showed no benefit for bone formation. Cell-laden poly(L-lactic acid) scaffolds without PRP required significantly greater force to displace from surrounding tissues than control (cell-free) scaffolds, but no differences were observed during push-out testing of coral scaffolds. For bone volume formation as analyzed by microcomputed tomography, significant positive overall effects were observed with bmMNC incorporation. These data suggest that bmMNCs may provide therapeutic advantages in bone tissue engineering applications without the need for culture, expansion, and purification.

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“…Identification of these factors will then allow the use of a higher concentration in order to amplify their effects not only on NPCs but also on BMSCs. These bioactive factors can then be administrated in clinics by simple injection or by the implantation of an injectable controlled release system, such as fibrin gel (Drinnan et al, 2010) or microspheres (Solorio et al, 2010;Park et al, 2009).…”

Section: Wwwecmjournalorg E Potier Et Al Notochordal Cells For Ivdmentioning

confidence: 99%

Potential application of notochordal cells for intervertebral disc regeneration: an in vitro assessment

Potier¹,

Vries²,

Doeselaar³

et al. 2014

eCM

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Recent studies suggest that notochordal cells (NCs) might be involved in intervertebral disc homeostasis, a role exploitable to counteract matrix degradation as observed during degeneration. This study aimed to evaluate the potential of NCs to promote matrix production by nucleus pulposus cells (NPCs) and to compare it to the currently proposed addition of bone marrow stromal cells (BMSCs). Using alginate beads, bovine NPCs were exposed for 28 d to porcine NC conditioned medium (NCCM); direct co-culture with porcine NCs or bovine BMSCs; or the combination of BMSCs and NCCM. Effects on cell proliferation, disc matrix production (proteoglycans, collagens) and disc matrix protein expression (aggrecan, collagen 1 and 2, SOX9) were determined and compared to TGFβ stimulation. NCCM strongly promoted NPC proliferation (x 2.2) and matrix production (x 3.9) to levels similar to that with TGFβ, whereas the direct addition of NCs had no effect. Co-culture of NPCs and BMSCs led to proteoglycan synthesis similar to NPCs alone, which was slightly improved by NCCM (x 1.5). Histological analysis confirmed biochemical data. Gene expression of analysed proteins remained stable for all groups and unaffected by medium conditions. NCs could substantially stimulate NPCs through factors secreted into conditioned medium and in levels similar to the addition of BMSCs. This study showed that molecular agents secreted by NCs constitute a promising alternative to the proposed "standard" injection of BMSCs for disc repair: their effects are similar, do not require the injection of a large number of cells and can be further amplified when the factors are identified.

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Multimodal release of transforming growth factor-β1 and the BB isoform of platelet derived growth factor from PEGylated fibrin gels

Cited by 63 publications

References 29 publications

Controlled delivery of SDF-1α and IGF-1: CXCR4⁺ cell recruitment and functional skeletal muscle recovery

Controlled delivery of SDF-1α and IGF-1: CXCR4⁺ cell recruitment and functional skeletal muscle recovery

Uncultured Marrow Mononuclear Cells Delivered Within Fibrin Glue Hydrogels to Porous Scaffolds Enhance Bone Regeneration Within Critical-Sized Rat Cranial Defects

Potential application of notochordal cells for intervertebral disc regeneration: an in vitro assessment

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Multimodal release of transforming growth factor-β1 and the BB isoform of platelet derived growth factor from PEGylated fibrin gels

Cited by 63 publications

References 29 publications

Controlled delivery of SDF-1α and IGF-1: CXCR4+ cell recruitment and functional skeletal muscle recovery

Controlled delivery of SDF-1α and IGF-1: CXCR4+ cell recruitment and functional skeletal muscle recovery

Uncultured Marrow Mononuclear Cells Delivered Within Fibrin Glue Hydrogels to Porous Scaffolds Enhance Bone Regeneration Within Critical-Sized Rat Cranial Defects

Potential application of notochordal cells for intervertebral disc regeneration: an in vitro assessment

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Controlled delivery of SDF-1α and IGF-1: CXCR4⁺ cell recruitment and functional skeletal muscle recovery

Controlled delivery of SDF-1α and IGF-1: CXCR4⁺ cell recruitment and functional skeletal muscle recovery