An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects

Abstract

The treatment of challenging fractures and large osseous defects presents a formidable problem for orthopaedic surgeons. Tissue engineering/regenerative medicine approaches seek to solve this problem by delivering osteogenic signals within scaffolding biomaterials. In this study, weCorrespondence to: Robert E. Guldberg, robert.guldberg@me.gatech.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptBiomaterials. Author manuscript; available in PMC 2012 January 1. introduce a hybrid growth factor delivery system that consists of an electrospun nanofiber mesh tube for guiding bone regeneration combined with peptide-modified alginate hydrogel injected inside the tube for sustained growth factor release. We tested the ability of this system to deliver recombinant bone morphogenetic protein-2 (rhBMP-2) for the repair of critically-sized segmental bone defects in a rat model. Longitudinal μ-CT analysis and torsional testing provided quantitative assessment of bone regeneration. Our results indicate that the hybrid delivery system resulted in consistent bony bridging of the challenging bone defects. However, in the absence of rhBMP-2, the use of nanofiber mesh tube and alginate did not result in substantial bone formation. Perforations in the nanofiber mesh accelerated the rhBMP-2 mediated bone repair, and resulted in functional restoration of the regenerated bone. μ-CT based angiography indicated that perforations did not significantly affect the revascularization of defects, suggesting that some other interaction with the tissue surrounding the defect such as improved infiltration of osteoprogenitor cells contributed to the observed differences in repair. Overall, our results indicate that the hybrid alginate/nanofiber mesh system is a promising growth factor delivery strategy for the repair of challenging bone injuries.

Hydrogel-based Delivery of rhBMP-2 Improves Healing of Large Bone Defects Compared With Autograft

“…Differential weightbearing is another possible concern with bilateral surgery. However, this concern is minimized by the fact that even untreated defects are sufficiently stabilized by the fixation plates to allow excellent mobility a few days postsurgery [8,14,27,28,34].…”

“…A porous electrospun polycaprolactone nanofiber mesh (NFM) sheet (12 9 19 mm) with 1-mm diameter perforations was preformed into a tube and positioned around the proximal and distal stumps of the femur such that it completely enclosed the defect space and spatially retained the delivered therapeutics within the defect space (Fig. 1B) [28]. The two treatments-autograft or NMA-rhBMP-2-were evaluated in the same animal with randomized allocation of treatment to the left or right limb for each group.…”

“…Torsional tests to failure were performed on samples harvested at 12 weeks postsurgery (n = 9 per treatment group) as established earlier [8,27,28,34]. Frozen samples were thawed at room temperature, dissected to remove all soft tissues surrounding the defects, and then the fixation plates were removed.…”

“…The widespread use of recombinant human BMP-2 (rhBMP-2) highlights its capability to augment large segmental bone defect repair, especially in the context of animal studies, with BMP-2 supplementation showing improved healing compared with allograft and ceramic fillers [25,46]. Concerns about BMP-2 side effects, optimal delivery scaffolds, and BMP-2 release kinetics notwithstanding, rhBMP-2 delivered in an absorbable collagen sponge (ACS-rhBMP-2) has become a popular clinical alternative to bone grafting in the United States while tunable delivery systems with tailored BMP release kinetics are sought [28,47].…”

“…We have previously observed higher mineral content and biomechanical properties in critically sized femoral segmental defects treated with a perforated nanofiber mesh enclosing RGD-alginate and rhBMP-2 (NMA-rhBMP-2) hybrid delivery system at equivalent doses and with advantageous rhBMP-2 release kinetics as compared with ACS-rhBMP-2 [8,9,27,28]. However, its performance relative to autograft, the gold standard, is unknown.…”