William R. Walsh

Osteoinductive ceramics as a synthetic alternative to autologous bone grafting

Biomaterials can be endowed with biologically instructive properties by changing basic parameters such as elasticity and surface texture. However, translation from in vitro proof of concept to clinical application is largely missing. Porous calcium phosphate ceramics are used to treat small bone defects but in general do not induce stem cell differentiation, which is essential for regenerating large bone defects. Here, we prepared calcium phosphate ceramics with varying physicochemical and structural characteristics. Microporosity correlated to their propensity to stimulate osteogenic differentiation of stem cells in vitro and bone induction in vivo. Implantation in a large bone defect in sheep unequivocally demonstrated that osteoinductive ceramics are equally efficient in bone repair as autologous bone grafts. Our results provide proof of concept for the clinical application of “smart” biomaterials.

Structural Properties of the Intact and the Reconstructed Coracoclavicular Ligament Complex

Numerous procedures have been described for the operative management of acromioclavicular joint injuries, but surprisingly little information is available on the ultimate mechanical behavior of the native coracoclavicular ligament complex or on the various methods of reconstruction. We tested 19 fresh-frozen cadaveric bone-ligament-bone preparations of the coracoclavicular ligament in uniaxial tension at 25 mm/min until failure. Seven specimens were left intact, six had the trapezoid ligament sectioned, and six had the conoid ligament sectioned. Reconstruction of the coracoclavicular ligament was achieved using coracoacromial ligament transfers, woven polyester slings, suture anchors, and Bosworth screws; all reconstructions were also tested to failure. The intact coracoclavicular ligament failed by avulsion or midsubstance tear at 500 (134) N, with a stiffness of 103 (30) N/mm and elongation to failure of 7.7 (1.9) mm. There was no significant difference between the contributions of the conoid or trapezoid ligaments in this loading configuration. Coracoclavicular slings and suture anchors provided strength similar to that of the coracoclavicular ligament, but with significantly greater deformations (14 to 26 mm). Screw fixation resulted in comparable stiffness and superior strength to the coracoclavicular ligament, but only if bicortical purchase was obtained. Coracoacromial ligament transfers were the weakest and least stiff, and augmentation with another form of coracoclavicular fixation is recommended. These results provide a useful baseline for comparison of the initial performance of reconstructive techniques with the performance of the native coracoclavicular ligament.

Mechanism of initial attachment of cells derived from human bone to commonly used prosthetic materials during cell culture

The suitability of polymeric biomaterials as surfaces for the attachment and growth of cells has often been investigated in cell culture. In this study the contribution that serum fibronectin (Fn) or vitronectin (Vn) make to the attachment and spreading of cells cultured from explanted human bone (bone-derived cells) during the first 90 min of culture was determined for metallic and ceramic surfaces. The requirement for Fn or Vn for attachment and spreading of bone-derived cells onto stainless steel 316 (SS), titanium (Ti) and alumina (Al2O3) and to polyethyleneterephthalate (PET) was directly tested by selective removal of Fn or Vn from the serum prior to addition to the culture medium. Attachment and spreading of bone-derived cells onto SS, Ti and Al2O3 surfaces were reduced by 73-83% when the cells were seeded in medium containing serum from which the Vn had been removed. Cell attachment and spreading on these surfaces when seeded in medium containing Fn-depleted serum (which contained Vn) were not reduced to the same extent as in the medium containing Vn-depleted serum. The bone-derived cells failed to attach to the surfaces to the same extent when seeded in medium containing serum depleted of both Vn and Fn. Our results show that for human bone-derived cells, the attachment and spreading of cells onto SS, Ti and Al2O3 as well as PET during the first 90 min of a cell culture attachment assay are a function of adsorption of serum Vn onto the surface.

Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage

The microarchitecture of bone is regulated by complex interactions between the bone‐forming and resorbing cells, and several compounds regulate both actions. For example, vitamin D, which is required for bone mineralization, also stimulates bone resorption. Transgenic mice overexpressing the vitamin D receptor solely in mature cells of the osteoblastic bone‐forming lineage were generated to test the potential therapeutic value of shifting the balance of vitamin D activity in favor of bone formation. Cortical bone was 5% wider and 15% stronger in these mice due to a doubling of periosteal mineral apposition rate without altered body weight or calcium homeostatic hormone levels. A 20% increase in trabecular bone volume in transgenic vertebrae was also observed, unexpectedly associated with a 30% reduction in resorption surface rather than greater bone formation. These findings indicate anabolic vitamin D activity in bone and identify a previously unknown pathway from mature osteoblastic cells to inhibit osteoclastic bone resorption, counterbalancing the known stimulatory action through immature osteoblastic cells. A therapeutic approach that both stimulates cortical anabolic and inhibits trabecular resorptive pathways would be ideal for treatment of osteoporosis and other osteopenic disorders.—Gardiner, E. M., Baldock, P. A., Thomas, G. P., Sims, N. A., Henderson, N. K., Hollis, B., White, C. P., Sunn, K. L., Morrison, N. A., Walsh, W. R., Eisman, J. A. Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage. FASEB J. 14, 1908–1916 (2000)

Morphometric and mechanical evaluation of titanium implant integration: Comparison of five surface structures

Achieving a stable bone-implant interface is an important factor in the long-term outcome of joint arthroplasty. In this study, we employed an ovine bicortical model to compare the bone-healing response to five different surfaces on titanium alloy implants: grit blasted (GB), grit blasted plus hydroxyapatite (50 microm thick) coating (GBHA), Porocoat(R) (PC), Porocoat(R) with HA (PCHA) and smooth (S). Push-out testing, histology, and backscatter scanning electron microscope (SEM) imaging were employed to assess the healing response at 4, 8, and 12 weeks. Push-out testing revealed PC and PCHA surfaces resulted in significantly greater mechanical fixation over all other implant types at all time points (p <.05). HA coating on the grit-blasted surface significantly improved fixation at 8 and 12 weeks (p <.05). The addition of HA onto the porous coating did not significantly improve fixation in this model. Quantification of ingrowth/ongrowth from SEM images revealed that HA coating of the grit-blasted surfaces resulted in significantly more ongrowth at 4 weeks (p <.05).

Resurfacing of the glenoid in total shoulder arthroplasty : A comparison, at a mean of five years, of prostheses inserted with and without cement

BACKGROUND Clinically evident loosening of a glenoid component inserted with cement in total shoulder arthroplasty is infrequent, but radiographic changes that indicate loosening at the implant-bone interface are common and have been associated with functional limitation. We compared the results of total shoulder arthroplasties in which the glenoid implant had been inserted with cement with those of arthroplasties in which a bone-ingrowth glenoid implant had been inserted without cement. METHODS The results of eighty-six consecutive total shoulder arthroplasties, performed by the same surgeon, were retrospectively reviewed between four and seven years after the operation. Fifty-eight shoulders in which the primary glenoid implant was in situ were assessed with use of the Simple Shoulder Test and Short Form-36 questionnaires, clinical examination, and fluoroscopic imaging of the glenoid implant-bone interface. Thirty-two of the glenoid components had been fixed with cement and twenty-six, without cement. RESULTS Complications occurred in 16 percent (fourteen) of the eighty-six shoulders, and 9 percent (eight) of the shoulders needed a revision operation. None of the revisions were done because of loosening of the glenoid component. Five of the eight revisions involved implants that had been inserted without cement. Three of these implants were revised because of early instability and two, because the polyethylene component had separated from the metal tray of the glenoid implant. With the numbers available, we could not detect any significant differences between the groups with respect to pain, range of motion, function of the shoulder, or general health. Radiographic analysis demonstrated a high level of interobserver agreement (kappa = 0.89). Radiolucent lines were observed after 41 percent (thirteen) of the thirty-two arthroplasties performed with cement compared with 23 percent (six) of the twenty-six arthroplasties performed without cement. The proportion of implants classified as probably loose was approximately three times greater in the group in which cement had been used. Eccentric wear of the posterior rim of the metal tray and focal osteolysis under the metal tray were observed in the group in which the component had been inserted without cement; these findings may indicate a potential for progression of radiographic loosening with increased durations of follow-up. CONCLUSIONS We concluded that, despite the higher rate of early complications, the intermediate-term outcomes of arthroplasties in which the glenoid implant is inserted without cement are comparable with those of arthroplasties with cementing of the glenoid component.

Fracture healing in a rat osteopenia model.

Fracture healing is influenced by mechanical and biologic factors. The capacity for fracture repair has been reported to decrease with age, although the risk of fracture increases with age. Fracture healing in an animal model of postmenopausal osteoporosis or osteopenia would provide a useful technique to evaluate and develop new treatment protocols. The authors examined the tensile and bending properties of healing femoral fractures in normal and ovariectomized rats. Mechanical data from tensile and bending tests indicate ovariectomy impairs fracture healing, which was confirmed through histologic study. Bending and tensile data provide useful information concerning the mechanical properties of the healing fracture. Tensile tests were noted to be sensitive indicators of the properties of the healing fracture.

An experimental model of femoral condylar defect leading to osteoarthrosis

Summary: The acute treatment of articular step-off injuries is based largely on reduction criteria, because the presence of residual incongruity has been correlated with the development of posttraumatic arthrosis (PTA). However, this association has not been demonstrated on a prospective basis. Using the rabbit femoral condyle, we developed a surgical model of articular condylar defect without sacrificing the axial alignment or inherent stability of the knee joint. Twenty weeks after the creation of 5-mm femoral condylar defects, progressive osteoarthritic changes were confirmed by radiographic, histological, and biochemical parameters. Osteophytes were observed on the medial aspect of operated knee joints in 67% of cases. Femoral and tibial articular cartilage at the site of the condylar defect exhibited fibrillation, hypocellularity, and severe loss of safranin-0 staining. Focal areas of cartilage were denuded or replaced by pannus. In no case was femoral congruity restored by cartilage repair. Statistically significant decreases in proteoglycan content were demonstrated for cartilage sampled from the weight-bearing region of the condylar defect and from the tibial surface directly beneath it. These changes resemble those arising from previously reported models of osteoarthrosis. We present the model as a valid tool for the study of articular condylar defect and its role in the development of PTA.

Type 2 fractures of the distal clavicle: A new surgical technique

Neer type 2 fractures of the distal clavicle have a high rate of nonunion and delayed union. In this series nine cases of coracoclavicular ligament reconstruction with Dacron graft material led to union at the fracture site. All patients had no symptoms and returned to full activity. This technique allows for stable fixation with early mobilization and return to work and sports.

Biomechanical evaluation of interference screw fixation in a bovine patellar bone-tendon-bone autograft complex for anterior cruciate ligament reconstruction

A bovine model was developed for biomechanical evaluation of anterior cruciate ligament (ACL) reconstruction using patellar bone-tendon-bone (b-t-b) autograft to examine the differences in time zero fixation mechanical properties of different interference screw lengths and diameters. The surgical technique of interference screw fixation of the b-t-b complex performed clinically was reproduced in a controlled animal model. The femur-patellar tendon graft-tibia complex was tested with anterior displacement of the tibia in 30 degrees of knee flexion to allow examination of the femoral and tibial fixation properties simultaneously. The statistical model concurrently explored differences between screw length and diameter while accounting for variations between graft properties. No statistically significant differences were found between the 7- and 9-mm screws with respect to peak load or energy to failure when using a 10-mm triangular graft in a 10-mm tunnel. The 7- and 9-mm screws were superior to the 5.5-mm screws with respect to these same parameters. Based on our results, the 7-mm interference screws can be used with equal confidence as the 9-mm screw, and the 20-mm length can be similarly exchanged for 30-mm length for patellar b-t-b graft fixation.