Mandibular defect repair by TGF- β and IGF-1 released from a biodegradable osteoconductive hydrogel
ABSTRACT Bone regeneration is crucial in the healing of defects in the craniofacial complex. The ability of transforming growth factor-beta1 (TGF-beta1) and insulin-like growth factor-1 (IGF-1), incorporated into a hydrogel scaffold to induce bone regeneration, was evaluated in a rat mandible defect model.
Hydrogel scaffolds containing either transforming growth factor-beta1 (TGF-beta1), insulin-like growth factor-1 (IGF-1), TGF-beta+ IGF-1, or saline, were implanted in rat mandibular bone defects. In a control group the defects were treated by saline alone. Bone defect healing was tested after 3 and 6 weeks by radiology and morphology.
Soft tissue radiographs indicated that the area of new bone formation increased gradually after 3 and at 6 weeks. The percentage of closure after 3 weeks was less than the percentage closure after 6 weeks. The amount of calcified material in the TGF-beta and TGF-beta+IGF-1-treated groups had increased more than in the saline-containing hydrogel and control (saline-treated) defects. The percentages of defect closures were 37, 38, 24, 14, and 11% after 3 weeks, and 94, 91, 84, 72, and 29% after 6 weeks, in the TGF-beta+IGF-1, TGF-beta, IGF-1, saline containing hydrogel and saline-treated animals, respectively. Three-dimensional computerized tomography (3D CT) images showed that the 3D shape of the bones was restored. Morphological analysis of the defects treated with hydrogel containing TGF-beta, IGF-1 or TGF-beta+IGF-1 revealed significant bone formation after 6 weeks.
It is concluded that the hydrogel scaffold impregnated with growth factors can induce bone regeneration and is therefore a promising surgical tool for enhancement of surgical repair of bone defects.
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ABSTRACT: The repair of bone defects in reconstructive surgery has significant limitations. Donor site morbidity, limited supply of autograft, and risks and complications associated with allografting and synthetic bone substitutes are among the most significant. In an effort to address these problems, the search for an ideal bone replacement has led to the development of a new method of poly(lactide-co-glycolide) (PLGA) foam processing, enabling the production of a biodegradable scaffold with similar porosity to human trabecular bone. In this study, these scaffolds were evaluated for bone repair in vivo in a femoral critical-sized segmental defect in New Zealand White (NZW) rabbits. Three groups of nine animals were investigated. In the first group, the critical-sized defects were empty. Scaffolds alone were implanted in the second group, whereas autologous bone marrow cell-loaded scaffolds were implanted in the third group. Animals ambulated freely for 8 weeks after surgery, and bone formation throughout the defects was serially assessed radiographically and quantified using a bone formation index (BFI) measure. Postmortem radiography and histology were also undertaken to examine bone formation. There was a significant effect of applying this technology to the amount of bone formed in the defects as determined by the BFI (F = 3.41, P < 0.05). The mean BFI for the cell-loaded scaffolds was greater than for the control group at all measured time points (2-, 4-, 6-, and 8-week radiographs). This difference was significant for the 2- and 8-week radiographs (P < 0.05). Qualitative histological assessment confirmed these findings. We concluded from these findings that these PLGA scaffolds loaded with marrow-derived progenitor cells yield significant bone formation in a critical-sized rabbit femoral defect. This technology comprising a novel scaffold design and autologous cells may provide an alternative to current strategies for reconstruction of bony defects.Journal of Craniofacial Surgery 05/2003; 14(3):324-32. · 0.69 Impact Factor
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ABSTRACT: This paper describes the sustained release of transforming growth factor β1 (TGF-β1) from a biodegradable hydrogel based on polyion complexation for the enhancement of bone regeneration activity. Basic TGF-β1 was adsorbed onto the biodegradable hydrogel of acidic gelatin with an isoelectric point of 5.0 by an electrostatic interaction. The TGF-β1 could not be adsorbed onto basic gelatin. When acidic gelatin hydrogels incorporating 125I-labeled TGF-β1 were implanted into the back subcutis of mice, the radioactivity decreased with time and the in vivo retention of TGF-β1 was prolonged with a decrease in the water content of hydrogels. The higher the water content of hydrogels, the faster their biodegradation. The in vivo retention of TGF-β1 correlated well with that of gelatin hydrogels, indicating that TGF-β1 was released from the gelatin hydrogel as a result of hydrogel biodegradation. The ability of TGF-β1-incorporated into acidic gelatin hydrogels to induce bone regeneration was evaluated in a rabbit calvarial defect model. Eight weeks after treatment, the gelatin hydrogels with water contents of 90 and 95 wt% induced significantly high bone regeneration compared with those with lower and higher water contents and free TGF-β1. This indicates that the sustained release of TGF-β1 from the hydrogel with suitable in vivo degradability is necessary to effectively enhance its osteoinductive function. Rapid hydrogel degradation will result in a retention time of TGF-β1 which is too short to induce bone regeneration. It is possible that the slow degradation of the hydrogel physically blocked TGF-β1-induced bone regeneration at the skull defect. It can be concluded that the gelatin hydrogel is a promising matrix of TGF-β1 release to induce skull bone regeneration.Journal of Controlled Release 03/2000; · 7.63 Impact Factor
Article: Tissue engineers build new bone.[show abstract] [hide abstract]
ABSTRACT: Bone repair may be one of the first major applications of tissue engineering; efforts to encourage the growth of new bone using novel matrices, bone morphogenic proteins, gene therapy, and stem cells are all showing promise. But the commercial stakes are so high that some researchers are worried that patent claims, and a reluctance to test competing technologies in combination, could delay progress in the field.Science 10/2000; 289(5484):1498-500. · 31.03 Impact Factor