Background Infectious complications of musculoskeletal trauma are an important factor contributing to patient morbidity. Biofilm-dispersive bone grafts augmented with D-amino acids (D-AAs) prevent biofilm formation in vitro and in vivo, but the effects of D-AAs on osteocompatibility and new bone formation have not been investigated.Questions/purposes We asked: (1) Do D-AAs hinder osteoblast and osteoclast differentiation in vitro? (2) Does local delivery of D-AAs from low-viscosity bone grafts inhibit new bone formation in a large-animal model? Methods Methicillin-sensitive Staphylococcus aureus and methicillin-resistant S aureus clinical isolates, mouse bone marrow stromal cells, and osteoclast precursor cells were treated with an equal mass (1:1:1) mixture of D-Pro:DMet:D-Phe. The effects of the D-AA dose on biofilm inhibition (n = 4), biofilm dispersion (n = 4), and bone marrow stromal cell proliferation (n = 3) were quantitatively measured by crystal violet staining. Osteoblast differentiation was quantitatively assessed by alkaline phosphatase staining, von Kossa staining, and quantitative reverse transcription for the osteogenic factors a1Col1 and Ocn (n = 3). Osteoclast differentiation was quantitatively measured by tartrate-resistant acid phosphatase staining (n = 3). Bone grafts augmented with 0 or 200 mmol/L D-AAs were injected in ovine femoral condyle defects in four sheep. New bone formation was evaluated by lCT and histology 4 months later. An a priori power analysis indicated that a sample size of four would detect a 7.5% difference of bone volume/total volume between groups assuming a mean and SD of 30% and 5%, respectively, with a power of 80% and an alpha level of 0.05 using a two-tailed t-test between the means of two independent samples. Results Bone marrow stromal cell proliferation, osteoblast differentiation, and osteoclast differentiation were inhibited at D-AAs concentrations of 27 mmol/L or greater in a dose-responsive manner in vitro (p \ 0.05). InThe institution of one or more of the authors (SAG, FE, JCW) has received, during the study period, funding from the Orthopaedic Extremity Trauma Research Program (SAG and JCW), the National Institute of Arthritis and Musculoskeletal Diseases (SAG, JCW, and FE), Medtronic, Inc (SAG); Oak Ridge Institute (AJH); and the National Institutes of Health (SAG). One of the authors certifies that he (SAG), or a member of his or her immediate family, has or may receive payments or benefits, during the study period, an amount less than USD 10,000, from Medtronic Spine and Biologics (Memphis, TN, USA).

Injectable bone grafts with strength exceeding that of trabecular bone could improve the management of a number of orthopaedic conditions. Ceramic/polymer composites have been investigated as weight-bearing bone grafts, but they are typically weaker than trabecular bone due to poor interfacial bonding. We hypothesized that entrapment of surface-initiated poly(ε-caprolactone) (PCL) chains on 45S5 bioactive glass (BG) particles within an in situ-formed polymer network would enhance the mechanical properties of reactive BG/polymer composites. When the surface-initiated PCL molecular weight exceeded the molecular weight between crosslinks of the network, the compressive strength of the composites increased 6- to 10-fold. The torsional strength of the composites exceeded that of human trabecular bone by a factor of two. When injected into femoral condyle defects in rats, the composites supported new bone formation at 8 weeks. The initial bone-like strength of BG/polymer composites and their ability to remodel in vivo highlight their potential for development as injectable grafts for repair of weight-bearing bone defects.

Bone grafts used to repair weight-bearing tibial plateau fractures often experience cyclic loading, and there is a need for bone graft substitutes that prevent failure of fixation and subsequent morbidity. However, the specific mechanical properties required for resorbable grafts to optimize structural compatibility with native bone have yet to be established. While quasi-static tests are utilized to assess weight-bearing ability, compressive strength alone is a poor indicator of in vivo performance. In the present study, we investigated the effects of interfacial bonding on material properties under conditions that re-capitulate the cyclic loading associated with weight-bearing fractures. Dynamic compressive fatigue properties of polyurethane (PUR) composites made with either unmodified (U-) or polycaprolactone surface-modified (PCL-) 45S5 bioactive glass (BG) particles were compared to a commercially available calcium sulfate and phosphate-based (CaS/P) bone cement at physiologically relevant stresses (5–30 MPa). Fatigue resistance of PCL-BG/polymer composite was superior to that of U-BG and CaS/P at higher stress levels for each of fatigue failure criteria, related to modulus, creep, and maximum displacement, and was comparable to human trabecular bone. Steady state creep and damage accumulation occurred during the fatigue life of the PCL-BG/PUR and CaS/P cement, whereas creep of U-BG/PUR primarily occurred at a low number of loading cycles. From crack propagation testing, fracture toughness or resistance to crack growth was significantly higher for the PCL-BG composite than for the other materials. Finally, the fatigue and fracture toughness properties were intermediate between those of trabecular and cortical bone. These findings highlight the potential of PCL-BG/polyurethane composites as weight-bearing bone grafts.