Introduction: The realisation that the medical and lateral menisci of the knee have important load-bearing and stability functions has stimulated orthopaedic surgeons to aim for preservation rather than excision if at all possible. The absence of meniscal tissue has been shown to increase load through the articular cartilage and ultimately accelerate the process of osteoarthritic degeneration. A major limitation is the relative avascularity of a large portion of the normal meniscus. McAndrews and Arnoczky reported in 1996 that repair of the white-white and even red-white zone remains a challenge. Monobutyrin is an angiogenic factor that has been used in the stimulation of healing burns and we hypothesized that it may have a positive effect on the healing meniscus.

The aim of the study was to determine the effects of 0 Ticron suture soaked in polyhydroxybutyrate (PHB) on the histological and mechanical properties of healing meniscal tears in the red-white zone in an established animal model.

Methods: A bilateral medical meniscal incision model was used in 21 adult sheep.

Results: We confirmed that the PHB had no deleterious effects on the mechanical properties of the suture prior to commencing the surgery. Mechanical testing of the menisci at the set time-points demonstrated a significantly stronger repair in the PHB-soaked group. Macroscopic appearances were graded and found to be improved with PHB soaked sutures. On histological examination there were features suggestive of a more intense healing response including angiogenesis.

Conclusions: We have concluded that the use of butyric acid has no deleterious effects on the mechanical properties of the suture used and has positive effects on meniscal healing. We recommend further examination of this exciting development.

Fracture healing involves many local and systemic regulatory factors. Progress in identifying signaling events downstream has been made with the discovery of a novel family of proteins, the Smad, as TGF-ß/activins/BMPs signal transducers. Smads are the vertebrate homologs of Mad (Mothers against decapentaplegic) gene from Drosophila and Sma genes from Caenorhabditis elegans. Smad-1, -2, -3, -5, -8 and -9 belong to the receptor-regulated class (R-Smad) which are activated by the TGF-ß type I and II receptors, forming heteromers with the common-mediator class (Co-Smad): Smad-4. Smad-6 and -7 (Anti-Smad) perform a negative regulatory or balancing role. Smad-2 and -3 regulate TGF-ß/activin effects, whilst Smad-1 and -5 work with BMPs. This study investigated the expression and localization of Smad proteins (Smad 1–6) and BMP-4 and -7 during fracture healing.

Eighteen 3-month old female CD-COB rats were used. A standard closed fracture was made in the mid-shaft of right femur using a 3-point bending device. The left limb served as the non-fracture control. The rats were divided into 3 groups (6 per group) and sacrificed at day 3, 10 and 28 after fracture. The femurs were harvested, fixed in buffered formalin for 48 hours and decalcified with 10% formic acid-formalin solution. The decalcified tissues were embedded in paraffin and 5μm sections were cut onto silane-coated slides. Representative slides from each block were stained with routine haematoxylin and eosin (H& E). Sections were cut for immunohistochemistry for protein marker expression by a standard procedure for Smads and BMP 4 and 7. Sections were viewed and analysed by colour video image analysis using a 40x objective, a 10x eyepiece, and a fixed frame of 128 × 128 pixels (49152.0 μm²). Ten fields per slide were examined.

Smad proteins (Smads 1, 4, and 6) were expressed during the early stages (day 3) of fracture healing by bone marrow stromal cells, osteoblasts, fibroblasts and chondrocytes located in the intramembranous and endochondral ossification regions around the fracture site. Differential expressions of individual Smads, particularly Smad 1 and Smad 6, at different time-points (Smad-1 was higher than Smad-6 at day 3, whilst Smad-6 was much higher than Smad-1 at day 10) suggest that Smad proteins are not simply BMP signal transducers. Smads may also be responsible for up- and/or down-regulation of transcriptional events during the intramembranous and endochondral ossification. Smad-4, a Co-SMAD, expression newly formed bone and cartilage suggests an additional function beyond the signal transduction in rat fracture healing. BMP-4 and BMP-7 were highly expressed at day 3 and 10. BMP-7 expression was greater than BMP-4 at day 3 but switched by day 10 (BMP-4 > BMP-7). Smads represent a new level where specific therapeutic strategies can be targeted considering the interactions with a number of BMPs.

Resorbable porous ceramics derived from chemically converted corals have been used successfully as bone graft substitutes for many years. Converted corals provide a 3D porous architecture that resembles cancellous bone with a pore diameter of 200–700 μm. The success of these corals as a bone graft substitute relies on vascular ingrowth, differentiation of osteoprogenitor cells, remodelling and graft resorption occurring together with host bone ingrowth into the porous microstructure or voids left behind during resorption. The resorption rate of the coral can be controlled by partial conversion to provide a hydroxyapatite (HA) layer via thermal modification. This study examined the resorption rates and bone formation of partially converted corals in a bilateral metaphyseal defect model.

Bilateral defects (5 mm x 15 mm) were created 3 mm below the joint line in the proximal tibia of 41 skeletally mature New Zealand white rabbits following ethical approval. Two variations of a calcium carbonate–HA coral (Pro Osteon 200 R, Interpore-Cross International, Irvine, CA) were examined with different HA thickness (200R; 14% or 200 RT; 28%). Empty defects (negative control) or defects filled with morcellised bone autograft from the defect sites (positive control) were performed. The tibiae were harvested at 6, 12, 24, 36 or 52 weeks, radiographed (standard x-rays and faxitron) in the anteroposterior and lateral planes. Tibias were processed for torsional testing and quantitative histomorphometry using back scattering scanning electron microscopy. Four additional rabbits were killed at time zero to determine the mechanical properties of the intact tibia (n=6 tibias) and 2 for tibias for time zero histomorphometry. Data were analysed using a 3-way analysis of variance.

No clinical complications were encountered in this study. Radiographic assessment revealed a progression in healing, implant resorption and bone infiltration. Cortical closure in the 200 R and 200RT treated defects was noted by 24 weeks. All specimens failed in torsional testing with a spiral fracture initiating at the distal defect site and extending into the distal diaphysis. Torsional properties reached intact control tibia levels by 24 weeks in both groups. No significant differences were noted between 200 R and 200 RT based on torsional data. SEM revealed progressive resorption of the calcium carbonate core of the 200 R and 200 RT with time, infiltration of bone and ingrowth to the HA layers. Time and measurement site (cortical versus cancellous) were significant for implant resorption, bone, and void. The thinner HA layer (200 R) resorbed more quickly compared to the thicker layer (200 RT) in the canal as well as cortical sites. Increased bone and decreased void were noted at the cortex measurement sites in the 200 R group at 24 weeks and in the 200 RT group at 12 and 24 weeks (p< 0.05). Implants were nearly completely resorbed by 52 weeks with only a few percent of implant remaining.

Methods: Sixty pseudo-capsular tissues from loose shoulder, hip and knee (20 each) arthroplasties and 30 capsular tissues from primary total joint arthroplasty (TJA) patients (10 each; 12 rheumatoid arthritis [RA], 18 osteo-arthrosis [OA]) were investigated for mRNA and protein expressions of IL-1ß (interleukin-1 b, IL-1Ra (interleukin-1 receptor antagonist), MMP 1 (matrix matalloproteinase-1)-, TIMP 2 (tissue inhibitor of MMPs-2) using in situ hybridisation and immunohistochemistry. Polyethylene and metal debris in the same sections were semi-quantified simultaneously.

Results: IL-1ß mRNA and proteins were expressed in most RA primary and revision tissues and were less expressed in OA primary tissues. In contrast, IL-1Ra mRNA was found in most primary OA tissues and less in RA primary and the revision tissues. The ratio of staining intensities of IL-1ß/IL-1Ra mRNA was higher in revision and primary RA tissues compared with the primary OA tissues. MMP-1 protein expression was correlated with the IL-1ß/IL-1Ra ratio. Polyethylene (PE) debris was found in 56 out of 60 of the revision tissues. Their sizes were different in the hip (mainly small, < 30 mm in diameter), the knee (mainly large, > 300 mm) and the shoulder (all sizes). The expressions of the detected factors were highly correlated with the concentration of the PE debris but with not their sizes.

Conclusions: The high ratio of IL-1ß/IL-1Ra in primary RA and revision tissues and its correlation with MMP-1 expression and PE debris concentration indicated that an over-expression of IL-1ß and/or regulation downwards of IL-1Ra is an important event in inflammatory disorders and the foreign body reaction in TJA. A therapeutic strategy with IL-1Ra, that has been considered in RA treatment may thus contribute to the longevity of prosthesis of a TJA.

Introduction: Abnormal fracture healing in aged, post-menopausal or ovariectomised patients remains a clinical problem. Understanding the distribution and regulation of biomolecular factors in fracture healing in oestrogen deficient rats may have clinical implications for developing novel therapeutic strategies for enhancing osteoporotic fracture healing. Our previous work demonstrated that bone morphogenetic proteins (BMPs), transforming growth factor beta (TGF-ß) and their signal transducers, Smads, played important roles in normal fracture healing. Insulin-like growth factor I (IGF-I) has been indicated playing a role in the maintenance of bone mass. Matrix metalloproteinases (MMPs) has been indicated to play a role in bone matrix degradation. Those factors in ovariectomised fracture healing have not yet been reported.

Aim: To investigate the expression of BMP-2, 7, TGF-ß, Smads1–7, IGF-I, IGF-I receptor 1a (IGF-IR1), MMPs and TIMPs by a quantitative immunohistochemistry in a fracture model in an ovariectomised rodent (OVX).

Methods: Age-matched, normal, female rats served as controls. The animals were sacrificed in groups of six at one, two, three, four and six weeks after the fracture.

Results: The highlights of our results were the lack of IGF-I in the early stage of fracture healing (up to two weeks) in OVX rats and the greater expression of MMP-1 in OVX rats at all groups when compared with the normal rats.

Conclusions: Our data suggested that the regulation downward of IGF-I in the OVX fractures resulted from estrogen deficiency and may have the function to stimulate MMP-1 activity. Over-expressed MMP-1 degraded collagen matrix in the cortex and inhibited the woven bone matrix formation during OVX fracture healing.