Sustained delivery of bioactive cytokine using a dense collagen gel vehicle

Premaraj, Sundaralingam; Mundy, Bethany L.; Morgan, D. A. L.; Winnard, Phillip L.; Mooney, Mark P.; Moursi, Amr M.

doi:10.1016/j.archoralbio.2005.08.008

Cited by 19 publications

(19 citation statements)

References 38 publications

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“…Although most CG have reportedly been able to enhance osteogenesis, [36][37][38] it is important to note that this particular gel exhibited an inherent inhibitory effect on cell proliferation, matrix production, and bone mineralization 39 and thus was proposed to prevent bone formation along cranial suture sites. 40 Contrary to these reports, however, we observed robust mineralization with the largest amount of ectopic bone in mice treated with these gels after being loaded with MDSC-B4. We further observed near-complete closure of the calvarial defects treated with this delivery construct, albeit with a 50% incidence of extensive bone regeneration.…”

Section: Usas Et Alcontrasting

confidence: 55%

Bone Regeneration Mediated by BMP4-Expressing Muscle-Derived Stem Cells Is Affected by Delivery System

Ūsas

Cooper

et al. 2009

Tissue Engineering Part A

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This study investigated the delivery of bone morphogenetic protein (BMP)4-secreting muscle-derived stem cells (MDSC-B4) capable of inducing bone formation in mice using collagen gel (CG), fibrin sealant (FS), and gelatin sponge carriers. After implanting these various cell-loaded scaffolds intramuscularly or into critical-size skull defects, we measured the extent of heterotopic ossification and calvarial defect healing over a 6-week period via radiographic, radiomorphometric, histological, and micro-computed tomography analyses. As expected, in the absence of MDSC-B4, there was no ectopic ossification and only minimal calvarial regeneration using each type of scaffold. Although CG and gelatin sponges loaded with BMP4-secreting cells produced the most ectopic bone, FS constructs produced bone with comparably less mineralization. In the mouse calvaria, we observed MDSC-B4-loaded scaffolds able to promote bone defect healing to a variable degree, but there were differences between these implants in the volume, shape, and morphology of regenerated bone. MDSC-B4 delivery in a gelatin sponge produced hypertrophic bone, whereas delivery in a CG and FS healed the defect with bone that closely resembled the quantity and configuration of native calvarium. In summary, hydrogels are suitable carriers for osteocompetent MDSCs in promoting bone regeneration, especially at craniofacial injury sites.

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Section: Usas Et Alcontrasting

confidence: 55%

Bone Regeneration Mediated by BMP4-Expressing Muscle-Derived Stem Cells Is Affected by Delivery System

Ūsas

Cooper

et al. 2009

Tissue Engineering Part A

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“…Optimal anti-Tgf-b2 antibody dosage and biodegradation kinetics of the collagen vehicle were determined in vitro and has been reported by one of the coauthors (AMM). 50,59,77 Data Collection Somatic and skull growth data from threedimensional computed tomographic (3-D CT) scans and cephalographs were obtained from all rabbits at 10, 25, 42, and 84 days of age. At 84 days of age, approximately 80% to 90% of total calvarial and brain growth is completed in the rabbit.…”

Section: Surgerymentioning

confidence: 99%

Postoperative Anti-Tgf-β2 Antibody Therapy Improves Intracranial Volume and Craniofacial Growth in Craniosynostotic Rabbits

Mooney¹,

Losken²,

Moursi

et al. 2007

Journal of Craniofacial Surgery

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Postoperative resynostosis and secondary craniofacial growth abnormalities are common sequelae after craniofacial surgery. It has been suggested that an overexpression of transforming growth factor-beta2 (Tgf-beta2) may be related to craniosynostosis and contribute to postoperative resynostosis. Interference with Tgf-beta2 function using neutralizing antibodies may inhibit resynostosis and improve postoperative craniofacial growth; the present study was designed to test this hypothesis. Twenty-nine New Zealand white rabbits with bilateral coronal suture synostosis were used: 1) suturectomy controls (n=9); 2) suturectomy with nonspecific, control IgG antibody (n=9); and 3) suturectomy with anti-Tgf-beta2 antibody (n=11). At 10 days of age, a 3 mm x 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with 0.1 cc of a slow resorbing collagen gel mixed with either IgG (100 microg/suture) or anti-Tgf-beta2 (100 microg/suture). Three-dimensional computed tomography scan reconstructions of the skulls and cephalographs were obtained at 10, 25, 42, and 84 days of age. Computed tomography scan data revealed patent suturectomy sites and significantly (P<0.05) greater intracranial volumes by 84 days of age in rabbits treated with anti-Tgf-beta2 compared with controls. Cephalometric analysis revealed significant (P<0.05) differences in craniofacial, cranial vault, and cranial base growth by 84 days of age in rabbits treated with anti-Tgf-beta2 compared with controls. These data support the initial hypothesis that interference with Tgf-beta2 function inhibited postoperative resynostosis and improved cranial vault growth in this rabbit model. Thus, this biologically based therapy may be a potential surgical adjunct in the treatment of infants with craniosynostosis.

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“…The authors suggested that this was probably not an effect of the IgG but rather was due to the presence of the collagen vehicle itself in the suturectomy site, which may have had an osteoinhibitory effect on reossification of the suturectomy site during degradation (Mooney et al, 2007a). A recent in vitro study (Premaraj et al, 2006) also has shown that the collagen vehicle alone had a short-term inhibitory effect on osteoblast cell number in culture. Because the ultimate goal of this research is to inhibit postoperative resynostosis and to improve craniofacial growth, this should not be viewed as a confounding variable, although future studies designed to facilitate osteogenesis using various growth factors delivered by this collagen vehicle should take this into consideration (Mooney et al, ,2007a(Mooney et al, ,2007bPremaraj et al, 2006).…”

Section: Discussionmentioning

confidence: 94%

“…A recent in vitro study (Premaraj et al, 2006) also has shown that the collagen vehicle alone had a short-term inhibitory effect on osteoblast cell number in culture. Because the ultimate goal of this research is to inhibit postoperative resynostosis and to improve craniofacial growth, this should not be viewed as a confounding variable, although future studies designed to facilitate osteogenesis using various growth factors delivered by this collagen vehicle should take this into consideration (Mooney et al, ,2007a(Mooney et al, ,2007bPremaraj et al, 2006). Ideally, the effects of collagen alone should be compared experimentally with treatment with collagen plus Tgf-β2 inhibition to delineate more clearly the contribution of each material to bone growth.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Craniofacial Phenotype in Craniosynostotic Rabbits Treated with Anti–Tgf-β2 at Suturectomy Site

Frazier

Mooney

Losken

et al. 2008

The Cleft Palate Craniofacial Journal

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Objective-Overexpression of transforming growth factor-beta 2 has been associated with craniosynostosis and resynostosis following surgery. We examined the effects of localized transforming growth factor-beta 2 inhibition on craniofacial phenotype in rabbits with craniosynostosis.Design-Twenty-five New Zealand white rabbits with bilateral coronal craniosynostosis were divided into three treatment groups: (1) suturectomy control (n = 8); (2) suturectomy with nonspecific, control immunoglobulin G antibody (n = 6); and (3) suturectomy with anti-transforming growth factor-beta 2 antibody (n = 11). At 10 days of age, a coronal suturectomy was performed on all rabbits. The sites in groups 2 and 3 were immediately filled with a slow-resorbing collagen gel mixed with either immunoglobulin G or anti-transforming growth factor-beta 2 antibody. Computed tomography scans of each rabbit were acquired at ages 10, 25, and 84 days. Craniofacial landmarks were collected from three-dimensional computed tomography reconstructions, and growth and form were compared among the three groups.Results-Rabbits treated with anti-transforming growth factor-beta 2 antibody differed in form at 84 days of age compared with suturectomy control rabbits, specifically in the snout and posterior neurocranium. Growth in some areas of the skull was greater in rabbits from the anti-transforming NIH Public Access Author ManuscriptCleft Palate Craniofac J. Author manuscript; available in PMC 2010 March 11. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript growth factor-beta 2 group than in suturectomy control rabbits, but not significantly greater than in IgG control rabbits.Conclusions-We find support for the hypothesis that transforming growth factor-beta 2 inhibition alters adult form, but these changes do not appear to be localized to the suturectomy region. Slight differences in form and growth between the two control groups suggest that the presence of the collagen vehicle itself may affect skull growth.Keywords coronal suturectomy; craniosynostosis; craniofacial; rabbits; Tgf-β2Craniosynostosis (i.e., premature fusion of one or more cranial sutures) impedes normal growth and development of the neurocranium and may result in associated abnormalities of the craniofacial complex (Babler, 1989; Cohen, 2000c;Richtsmeier, 2002). In humans, 95% of brain growth is completed by 6 years of age (Enlow, 1990), by which time the metopic suture has fused in about 90% of individuals. The remaining cranial sutures will not fuse fully until well into adulthood (Cohen, 2000b). The full impact of craniosynostosis on neurological development is not well understood. The early closure of even a single suture is widely thought to increase intracranial pressure (ICP) (Renier, 1989;Gault et al., 1992;Campbell et al., 1995;Thompson et al., 1995;Pollack et al., 1996;Hudgins et al., 1998;Mooney et al., 1998aMooney et al., , 1999 Jane and Persing, 2000;Fellows-Mayle et al., 2004), although this finding has been questioned because normative I...

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Sustained delivery of bioactive cytokine using a dense collagen gel vehicle

Cited by 19 publications

References 38 publications

Bone Regeneration Mediated by BMP4-Expressing Muscle-Derived Stem Cells Is Affected by Delivery System

Bone Regeneration Mediated by BMP4-Expressing Muscle-Derived Stem Cells Is Affected by Delivery System

Postoperative Anti-Tgf-β2 Antibody Therapy Improves Intracranial Volume and Craniofacial Growth in Craniosynostotic Rabbits

Comparison of Craniofacial Phenotype in Craniosynostotic Rabbits Treated with Anti–Tgf-β2 at Suturectomy Site

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