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Traumatic injuries, cancer treatment, and congenital abnormalities are often associated with abnormal bone shape or segmental bone loss. Restoration of normal structure and function in these cases requires replacement of the missing bone that may be accomplished by surgical transfer of natural tissue from an uninjured location elsewhere in the body. However, this procedure is limited by availability, adequate blood supply, and secondary deformities at the donor site. One strategy to overcome these problems is to develop living tissue substitutes based on synthetic biodegradable polymers. Three methods of bone regeneration using biodegradable polymers are being studied in our laboratory: tissue induction, cell transplantation, and fabrication of vascularized bone flaps. Injectable polymers are used for filling skeletal defects and guiding bone tissue growth. Their main advantage is minimizing the surgical intervention or the severity of the surgery. Polymer-cell constructs also hold great promise in the field of tissue engineering. They provide a scaffold on which cells grow and organize themselves. As the cells begin to secrete their own extracellular matrix, the polymer degrades and is eventually eliminated from the body, resulting in completely natural tissue replacement. Bone flaps can be fabricated ectopically into precise shapes and sizes. With an attached vascular supply, these flaps can be transferred into areas deficient in vascularity. This article discusses polymer concepts regarding bone tissue engineering and reviews recent advances of our laboratory on guided bone regeneration using biodegradable polymer scaffolds.

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This study was designed to investigate the in vivo biodegration and biocompatibility of a poly(propylene fumarate) (PPF)-based orthopedic biomaterial. The effects of varying the PPF to N-vinyl pyrrolidinone ratio and PPF to beta-tricalcium phosphate content were studied. The composite mechanical properties and local tissue interactions were analyzed over 12 weeks. An initial increase in both compressive modulus and strength was seen for composite formulations that incorporated beta-tricalcium phosphate. The samples incorporating a higher PPF to N-vinyl pyrrolidinone ratio reached a maximal compressive strength of 7.7 MPa and a maximal compressive modulus of 191.4 MPa at 3 weeks. The lower PPF to N-vinyl pyrrolidinone ratio samples gained a maximum compressive strength of 7.5 MPa initially and a compressive modulus of 134.0 MPa at 1 week. At 6 weeks, all samples for formulations incorporating beta-tricalcium phosphate crumbled upon removal and were not mechanically tested. Samples that did not incorporate beta-tricalcium phosphate were very weak and insufficient for bone replacement at the 4-day time point and beyond. Tissue interactions resulted in a mild inflammatory response at the initial time points and mature fibrous encapsulation by 12 weeks.

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We investigated the effects of the time course of addition of osteogenic supplements dexamethasone, beta-glycerolphosphate, and L-ascorbic acid to rat marrow stromal cells, and the exposure time on the proliferation and differentiation of the cells. It was the goal of these experiments to determine the time point for supplement addition to optimize marrow stromal cell proliferation and osteoblastic differentiation. To determine this, two studies were performed; one study was based on the age of the cells from harvest, and the other study was based on the duration of exposure to supplemented medium. Cells were seen to proliferate rapidly at early time points in the presence and absence of osteogenic supplements as determined by 3H-thymidine incorporation into the DNA of replicating cells. These results were supported by cell counts ascertained through total DNA analysis. Alkaline phosphatase (ALP) activity and osteocalcin production at 21 days were highest for both experimental designs when the cells were exposed to supplemented medium immediately upon harvest. The ALP levels at 21 days were six times greater for cells maintained in supplements throughout than for control cells cultured in the absence of supplements for both studies, reaching an absolute value of 75 x 10(-7) micromole/min/cell. Osteocalcin production reached 20 x 10(-6) ng/cell at 21 days in both studies for cells maintained in supplemented medium throughout the study, whereas the control cells produced an insignificant amount of osteocalcin. These results suggest that the addition of osteogenic supplements to marrow-derived cells early in the culture period did not inhibit proliferation and greatly enhanced the osteoblastic phenotype of cells in a rat model.

We investigated the crosslinking characteristics of an injectable composite paste of poly(propylene fumarate) (PPF), N-vinyl pyrrolidinone (N-VP), benzoyl peroxide (BP), sodium chloride (NaCl), and beta-tricalcium phosphate (beta-TCP). We examined the effects of PPF molecular weight, N-VP/PPF ratio, BP/PPF ratio, and NaCl weight percent on the crosslinking temperature, heat release upon crosslinking, gel point, and the composite compressive strength and modulus. The maximum crosslinking temperature did not vary widely among formulations, with the absolute values falling between 38 degrees and 48 degrees C, which was much lower than that of 94 degrees C for poly(methyl methacrylate) bone cement controls tested under the same conditions. The total heat released upon crosslinking was decreased by an increase in PPF molecular weight and a decrease in N-VP/PPF ratio. The gel point was affected strongly by the PPF molecular weight, with a decrease in PPF molecular weight more rapidly leading to a gel point. An increase in initiator concentration had the same effect to a lesser degree. The time frame for curing was varied from 1-121 min, allowing the composite to be tailored to specific applications. The compressive strength and compressive modulus values increased with decreasing N-VP/PPF, increasing NaCl content, and increasing BP/PPF ratio. For all formulations, the compressive strength values fell between 1 and 12 MPa, and the compressive modulus values fell between 23 and 265 MPa. These data suggest that injectable PPF/beta-TCP pastes can be prepared with handling characteristics appropriate for clinical orthopedic applications and that the mechanical properties of the cured composites are suitable for trabecular bone replacement.