The morbidity associated with autogenous bone graft harvest and the recent concern regarding the transmission of live virus through use of allografts, have been the impetus for research into a variety of materials that could take the place of these standard materials for bone grafting. The positive results reported with various ceramics and/or bone derivatives suggest the possibility of a material with osteoconductive and/or osteoinductive properties for use with or in place of bone graft. This review discusses a variety of bone graft and bone graft substitute materials. Among the osteoconductive materials outlined are the hydroxyapatite and tricalcium phosphate ceramics as well as some reportedly osteoactive polymers. While osteoconduction is a favorable quality, much interest has focussed on the use of osteoinductive or osteogenic materials such as demineralized bone matrix or bone derivatives, that is, BMP, osteogenin, etc. It is increasingly apparent that these materials require a carrier vehicle for optimal expression of osteoactivity. Therefore, the review finishes with a comparison of the various materials suggested for use as carriers.Requests for reprints should be sent to

No abstract

Several clinical series, analyzing fracture healing in patients with diabetes mellitus (DM), demonstrated significant incidence of delayed union, non-union, and pseudarthrosis. In this study, analysis was performed to evaluate the effects of blood glucose (BG) control on fracture healing in the D M BB Wistar rat, a rat strain that represents a close homology to Type I DM in man. Our study showed decreased cell proliferation at the fracture site as well as decreased mechanical stiffness and bony content in the poorly controlled DM rats. To determine the effect of BG control, D M rats were treated with insulin sufficient to maintain physiologic BG levels throughout the course of the study. Values of cellular proliferation, biomechanical properties and callus bone content in tightly controlled DM animals were not significantly different from values of non-DM control values. This study suggests that insulin treatment with resultant improved BG control will ameliorate the impaired early and late parameters of D M fracture healing.

No abstract

This study analyzed the in vivo performance of composite degradable bone repair products fabricated using the TheriForm process, a solid freeform fabrication (SFF) technique, in a rabbit calvarial defect model at 8 weeks. Scaffolds were composed of polylactic-co-glycolic acid (PLGA) polymer with 20% w/w beta-tricalcium phosphate (beta-TCP) ceramic with engineered macroscopic channels, a controlled porosity gradient, and a controlled pore size for promotion of new bone ingrowth. Scaffolds with engineered macroscopic channels and a porosity gradient had higher percentages of new bone area compared to scaffolds without engineered channels. These scaffolds also had higher percentages of new bone area compared to unfilled control defects, suggesting that scaffold material and design combinations could be tailored to facilitate filling of bony defects. This proof-of-concept study demonstrated that channel size, porosity, and pore size can be controlled and used to influence new bone formation and calvarial defect healing.

The in vivo bone response of 3D periodic hydroxyapatite (HA) scaffolds is investigated. Two groups of HA scaffolds (11 mm diameter x 3.5 mm thick) are fabricated by direct-write assembly of a concentrated HA ink. The scaffolds consist of cylindrical rods periodically arranged into four quadrants with varying separation distances between rods. In the first group, HA rods (250 microm in diameter) are patterned to create pore channels, whose areal dimensions are 250 x 250 microm(2) in quadrant 1, 250 x 500 microm(2) in quadrants 2 and 4, and 500 x 500 microm(2) in quadrant 3. In the second group, HA rods (400 microm in diameter) are patterned to create pore channels, whose areal dimensions of 500 x 500 microm(2) in quadrant 1, 500 x 750 microm(2) in quadrants 2 and 4, and 750 x 750 microm(2) in quadrant 3. Each group of scaffolds is partially densified by sintering at 1200 degrees C prior to being implanted bilaterally in trephine defects of skeletally mature New Zealand White rabbits. Their tissue response is evaluated at 8 and 16 weeks using micro-computed tomography, histology, and scanning electron microscopy. New trabecular bone is conducted rapidly and efficiently across substantial distances within these patterned 3D HA scaffolds. Our observations suggest that HA rods are first coated with a layer of new bone followed by subsequent scaffold infilling via outward and inward radial growth of the coated regions. Direct-write assembly of 3D periodic scaffolds composed of micro-porous HA rods arrayed to produce macro-pores that are size-matched to trabecular bone may represent an optimal strategy for bone repair and replacement structures.

Diabetes mellitus is a common systemic disease that has been associated with poor fracture healing outcomes. The mechanism through which diabetes impairs bone regeneration is unknown. One possible mechanism may be related to either decreased or uncoordinated release of local growth factors at the fracture site. Indeed, previous studies have found reduced platelet-derived growth factor (PDGF) levels in the fracture callus of diabetic rats, suggesting that local application of PDGF may overcome the negative effects of diabetes and promote fracture healing. To test this hypothesis, low (22 mg) and high (75 ug) doses of recombinant human PDGF-BB (rhPDGF-BB) were applied directly to femur fracture sites in BB Wistar diabetic rats that were then compared to untreated or vehicle-treated animals. rhPDGF-BB treatment significantly increased early callus cell proliferation compared to that in control specimens. Low dose rhPDGF-BB treatment significantly increased callus peak torque values (p < 0.05) at 8 weeks after fracture as compared to controls. High dose rhPDGF-BB treatment increased callus bone area at 12 weeks postfracture. These data indicate that rhPDGF-BB treatment ameliorates the effects of diabetes on fracture healing by promoting early cellular proliferation that ultimately leads to more bone formation. Local application of rhPDGF-BB may be a new therapeutic approach to treat diabetes-impaired fracture healing. ß

No abstract