Healing bone lesion defects using injectable CaSO4 /CaPO4 -TCP bone graft substitute compared to cancellous allograft bone chips in a canine model.

CaSO4 /CaPO4 -TCP bone graft substitute has been shown to be effective for treatment of bone lesion defects, but its mechanical, histological, and radiographic characteristics have not been studied in direct comparison with a conventional treatment such as cancellous allograft bone. Thirteen canines had a critical-size axial defect created bilaterally into the proximal humerus. CaSO4 /CaPO4 -TCP bone graft substitute (PRO-DENSE™, Wright Medical Technology) was injected into the defect in one humerus, and an equal volume of freeze-dried cancellous allograft bone chips was placed in the contralateral defect. The area fraction of new bone, residual graft, and fibrous tissue and the compressive strength and elastic modulus of bone within the defects were determined after 6, 13, or 26 weeks and correlated with radiographic changes. The data were analyzed using Friedman and Mann-Whitney tests. There was more bone in defects treated with the CaSO4 /CaPO4 -TCP bone graft substitute compared to defects treated with cancellous bone allograft at all three time points, and the difference at 13 weeks was significant (p = 0.025). The new bone was significantly stronger and stiffer in defects treated with the CaSO4 /CaPO4 -TCP bone graft substitute compared to defects treated with cancellous bone allograft at 13 (p = 0.046) and 26 weeks (p = 0.025). At 26 weeks, all defects treated with CaSO4 /CaPO4 -TCP bone graft substitute demonstrated complete healing with new bone, whereas healing was incomplete in all defects treated with cancellous allograft chips. The CaSO4 /CaPO4 -TCP bone graft substitute could provide faster and significantly stronger healing of bone lesions compared to the conventional treatment using freeze-dried cancellous allograft bone. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 408-414, 2019.

Nanoscale surface modification by anodic oxidation increased bone ingrowth and reduced fibrous tissue in the porous coating of titanium-alloy femoral hip arthroplasty implants.

Hip arthroplasty femoral stems coated with Ti6Al4V beads were treated by anodic oxidation in H3 PO4 for enhanced bioactivity and were studied in a 6-month canine model to determine the effects of the treated surface on the ingrowth of bone and soft tissues. The area fractions of bone, marrow, and fibrous tissue in the porous coating of seven treated and seven untreated control implants were determined using histomorphological techniques. The area fraction of bone within the porous coating was greater for anodic oxide treated (23.6 ± 8.3%) compared to control implants (l2.7 ± 4.7%) (p = 0.013), and there was less fibrous tissue in the treated implants (18.0 ± 9.5%) compared to the controls (33.1 ± 7.9%) (p = 0.006). XPS, XRD, TEM, and SEM analyses of the treated implants revealed a 400 nm-thick titanium oxide layer of low crystallinity with an undulating surface, populated with more than 25 nm-size pores per square micrometer. There was no detectable increase in serum titanium or in generation of particulates locally compared to the control implants. Micro and nanoscale surface modification by anodic oxidation increased bone ingrowth and reduced fibrous tissue, which may extend the longevity of fixation, limiting pathways for particle migration, and impeding the progression of osteolysis and aseptic loosening of arthroplasty components. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 283-290, 2017.

Implantation of a titanium partial limb prosthesis in a white-naped crane (Grus vipio).

A female white-naped crane (Grus vipio) was presented with an open, oblique fracture of the distal right tarsometatarsus and concomitant vascular and nerve damage. Conventional fracture fixation repairs failed, which led to implantation of a custom titanium limb prosthesis. After subsequent revisions with 2 different prosthetic devices, limb function was ultimately restored but a later yolk embolism caused a circulatory compromise in the opposite leg, which necessitated euthanasia. Histopathologic results revealed limited ingrowth of bone into the porous coated implant, which indicated that a limb prosthesis may provide salvage for long-legged, heavy-bodied birds with fractures of the tarsometatarsus.

Vertebroplasty comparing injectable calcium phosphate cement compared with polymethylmethacrylate in a unique canine vertebral body large defect model.

BACKGROUND CONTEXT: Vertebroplasty was developed to mechanically reinforce weakened vertebral bodies. Polymethylmethacrylate (PMMA) bone cement has been most commonly used but carries risks of thermal injury and respiratory and cardiovascular complications. Calcium phosphate (CaP) offers the potential for biological resorption and replacement with new bone, restoring vertebral body mass and height. PURPOSE: To compare compressive strength, elastic modulus of the adjacent motion segments, and histologic response of vertebral bodies injected with either CaP or PMMA in a canine vertebroplasty model. STUDY DESIGN: By using a canine vertebroplasty model, two level vertebroplasties were performed at L1 and L3 and studied for 1 month (n=10) and 6 months (n=10). In each canine, one vertebral defect was randomly injected with either CaP cement (BoneSource; Stryker, Freiberg, Germany) or PMMA. METHODS: Twenty dogs had an iatrogenically created cavitary lesion at two nonadjacent levels injected with either CaP or PMMA. Canines from each group were tested mechanically (n=5) and histologically (n=5). Histology consisted of axial sections of the L1 and L3 vertebral bodies and high-resolution contact radiographs. Sections from each specimen were embedded in plastic without decalcification to study the bone-cement interface. Bone-cement interfaces were compared for evidence of necrosis, fibrosis, foreign body response, cement resorption, and new bone formation between the PMMA and CaP treatments groups. Mechanical compression testing was performed on specimens from the 1-month (n=5) and 6-month (n=5) time periods. The T13 vertebral body was used as an intact control for the destructive compression testing of L1 and L3. Each vertebral body was compressed to 50% of its original height under displacement control at 15 mm/min to simulate a nontraumatic loading situation. Force and displacement data were recorded in real time. RESULTS: Vertebral sites containing PMMA were characterized by a thin fibrous membrane. PMMA was detected within the trabeculae, vascular channels, and the spinal canal. Unlike PMMA, CaP underwent resorption and remodeling with vascular invasion and bone ingrowth. Woven and lamellar bone was found on the CaP cement surface, within the remodeled material, and on the surrounding trabeculae. Vertebral body compression strength testing revealed no significant difference in vertebral body height and compressive strength between PMMA and CaP. There was a trend for CaP-treated vertebrae to increase in compressive strength from 1 month to 6 months, whereas PMMA decreased compressive strength when compared with adjacent nontreated vertebrae. CONCLUSION: For both short and intermediate time periods, the injection of CaP cement can be an effective method to treat large vertebral defects. Early results indicate that CaP remodeling might result in the resorption of the majority of the cement with replacement by lamellar bone.

Bone ingrowth through porous titanium granulate around a femoral stem: histological assessment in a six-month canine hemiarthroplasty model.

The procedure of using of porous titanium granules for cementless fixation of a hip replacement femoral stem was studied in a hemiarthroplasty model in 10 canines for 6 months. A vibrating instrument was used to facilitate both the delivery and distribution of the irregularly shaped porous titanium granules into the femoral canal as well as the subsequent insertion of a titanium alloy stem into the intramedullary bed of granules. Histological examination revealed lamellar bone formation through the mantle of porous titanium granules in continuity with the surrounding cortex resulting in the formation of an integrated mantle of bone and titanium granulate around the prosthesis.

Increased bone formation using calcium sulfate-calcium phosphate composite graft.

Calcium phosphates (CaPO4) and faster-resorbing calcium sulfate (CaSO4) are successfully employed as synthetic bone grafts for treatment of contained defects. We used a canine critical-sized bone defect model to study an injectable CaSO4/CaPO4 composite graft that incorporated a matrix of CaSO4 and dicalcium phosphate dihydrate into which beta-tricalcium phosphate granules were distributed. The area fraction, ultimate compressive stress, and elastic modulus of restored bone and the relative rates of material resorption were compared between the CaSO4/CaPO4 composite graft and pure CaSO4 pellets and to normal canine bone. The area fraction of bone in stained sections and the ultimate compressive stress of the regenerated bone were greater using the CaSO4/CaPO4 composite graft compared to pure CaSO4 pellets after 13 and 26 weeks and were greater than normal bone. The elastic modulus of restored bone in defects treated with CaSO4/CaPO4 composite graft was greater than in defects treated with CaSO4 pellets after 26 weeks, but similar to specimens of normal bone. A small amount of CaSO4/CaPO4 composite graft and no CaSO4 pellets remained after 13 or 26 weeks. This novel CaSO4/CaPO4 composite holds promise for clinical applications where a strong, injectable, slower-resorbing, and biocompatible bone graft substitute would be advantageous.

Effects of implant material and plate design on tendon function and morphology.

Titanium implants are an alternative to stainless steel implants for internal fixation after fracture. The advantages of titanium include decreased implant stiffness, increased bio-compatibility, and diminished stress shielding. However, titanium has been implicated in tendon irritation and adhesions when used in the hand and wrist. We evaluated the relationship between extensor tendon morphology and dorsal plating of the distal radius in a canine model using distal radius pi plates made of stainless steel, titanium, and titanium alloy with a modified ramped edge design. We found marked histologic changes in the tendons and surrounding soft tissues including tendon deformation and degeneration (fibrillation, cartilage metaplasia, hypocellularity and hyalinization of blood vessels), peritendonous adhesions and neovascularity in the parenchyma. Only a minimal inflammatory cell infiltrate was identified and was limited to the tenosynovium and/or paratenon. No differences were identified between titanium and stainless steel implants and those with a ramped design. Although all animals lost wrist motion with time, no differences were observed between groups. Our results suggest that pi plate placement on the dorsal surface of the distal radius may lead to extensor tendon irritation and dysfunction. There is no evidence to suggest that this is specifically related to titanium or plate edge design.

Local and systemic levels of tobramycin delivered from calcium sulfate bone graft substitute pellets.

We asked if tobramycin-loaded calcium sulfate pellets could be used to maintain high local site antibiotic concentrations for an extended period with minimal systemic levels and without adverse effects on vital organs. Calcium sulfate pellets loaded with 10% tobramycin were implanted in contained medullary defects in the proximal humeri of canines. The number of pellets implanted was calculated to yield an equivalent human maximum prescribed dose, and 1.8-fold this dose. These doses converted to approximately 20 mg/kg, and 36 mg/kg, respectively, for the canine. Local and systemic tobramycin levels, pellet resorption, bone response, clinical pathology parameters, and histopathologic responses of potential target organs were analyzed to determine if there was any adverse response for a 28-day period. Serum tobramycin was elevated for less than one day while local levels remained elevated for at least 14 days, and in some animals, 28 days. Tobramycin delivered locally from calcium sulfate pellets had no apparent adverse effect on clinical pathology parameters or on any of the organs that were analyzed. In addition, bone formation and pellet resorption followed patterns typically seen with calcium sulfate materials.

Effect of hip hemiarthroplasty on articular cartilage and bone in a canine model.

The purpose of this study was to determine if acetabular articular cartilage damage occurs in the presence or absence of changes in subchondral plate thickness or porosity and trabecular bone architecture after hip hemiarthroplasty. Eight canines were sacrificed 6 months after receiving unilateral hemiarthroplasties in which a cobalt chrome alloy femoral head was used. The acetabular cartilage, subchondral plate, and trabecular bone were quantitatively evaluated. Although the articular cartilage in the treated hip showed gross and histologic degenerative changes, there were no differences in the treated and contralateral hips in any of the trabecular bone parameters or subchondral plate thickness. However, the subchondral plate porosity was increased 2.6-fold in the treated hip. Therefore, degradation of cartilage can occur in the absence of thickening of the subchondral plate or alterations in the supporting trabecular bone architecture. These observations provide a better understanding of the role that periarticular bone has in the degenerative process after hemiarthoplasty.

Effects of altered crystalline structure and increased initial compressive strength of calcium sulfate bone graft substitute pellets on new bone formation.

A new, modified calcium sulfate has been developed with a different crystalline structure and a compressive strength similar to many calcium phosphate materials, but with a resorption profile only slightly slower than conventional surgical-grade calcium sulfate. A canine bilateral defect model was used to compare restoration of defects treated with the modified calcium sulfate compared to treatment using conventional calcium sulfate pellets after 6, 13, and 26 weeks. The modified calcium sulfate pellets were as effective as conventional calcium sulfate pellets with regard to the area fraction and compressive strength of newly formed bone in the treated bone defects. Mechanical testing demonstrated that the initial compressive strength of the modified material was increased nearly three-fold compared to that of conventional surgical-grade calcium sulfate. This increase potentially allows for its use in a broader range of clinical applications, such as vertebral and subchondral defects.

An injectable calcium sulfate-based bone graft putty using hydroxypropylmethylcellulose as the plasticizer.

The addition of a plasticizer to synthetic bone graft substitutes can improve handling characteristics, injectability, and the ability to uniformly fill defects. Restoration of large medullary bone defects using an injectable calcium sulfate-based putty using hydroxypropylmethylcellose as the plasticizer was compared to conventional calcium sulfate paste in a canine model. Beginning 2 weeks following implantation, serial clinical and specimen radiographs demonstrated a similar progressive resorption of the implanted materials and replacement with new bone for both the putty and paste forms of calcium sulfate. The area fraction of new bone and remaining implant material in bone defects treated with the putty were not significantly different from defects treated with conventional calcium sulfate paste after 13 and 26 weeks. In addition to its handling characteristics, the putty was biocompatible and as effective as conventional calcium sulfate paste in achieving substantial bony restoration of a large, critical-size bone defect.

Restoration of large bone defects using a hard-setting, injectable putty containing demineralized bone particles compared to cancellous autograft bone.

An injectable, hard-setting, calcium sulfate-based putty containing demineralized bone matrix particles (AlloMatrix II, Wright Medical Technology, Inc, Arlington, Tenn) was compared to autogenous cancellous bone graft to evaluate healing in a canine model. Area fraction of new bone, modulus of elasticity, and compressive strength of new bone were evaluated, as was radiographic and histologic healing. Bilateral defects were created in the proximal humeri, and each defect was implanted with either the putty or autogenous bone according to a randomized schedule. Dogs were euthanized at 6, 13, and 26 weeks. The area fraction, modulus of elasticity, and compressive strength of newly formed bone was not significantly different between the putty and autogenous bone at 6, 13, or 26 weeks. The putty had excellent handling characteristics, was biocompatible, and was as effective as autograft bone in achieving near complete bony restoration of a large, critical-sized defect.

Osseous healing using injectable calcium sulfate-based putty for the delivery of demineralized bone matrix and cancellous bone chips.

Three formulations of injectable calcium sulfate-based putties containing demineralized bone matrix (DBM), 50% DBM/50% cancellous bone (CB) chips, and 30% DBM/70% CB were studied in canines. Four humeral defects per dog were implanted with one of each of the putty formulations while the fourth defect was left untreated. After 6 weeks, the dogs were euthanized. Radiographs and histology showed that the area fraction of new bone in the defects was greater for the three putty formulations than the untreated defects. The area of residual cancellous bone graft remaining in the defects was <10% in both CB putties. Residual calcium sulfate was not apparent in any of the histological sections. We conclude that fast-resorbing calcium sulfate-based putties are effective delivery means of bone graft materials for the successful restoration of bony defects.

Resorption evaluation of a large bolus of calcium sulfate in a canine medullary defect.

New bone formation and resorption of a calcium sulfate bone graft substitute implanted in five canines were evaluated in this study. Healing was assessed radiographically at 2, 6, and 13 weeks. At 13 weeks, the dogs were sacrificed, and the humeri were retrieved. High-resolution contact radiographs of the isolated humeri were obtained and the bones were sectioned for histology. Radiographically, the calcium sulfate appeared to be completely resorbed and replaced by bone at 13 weeks. Histological findings suggest that a residual amount of calcium sulfate remained, which may continue to act as an osteoconductive scaffolding. No adverse inflammatory response was observed.

Healing of large defects treated with calcium sulfate pellets containing demineralized bone matrix particles.

Calcium sulfate (OsteoSet, Wright Medical Technology, Inc, Arlington, Tenn) and calcium sulfate/demineralized bone matrix (DBM) pellets (OsteoSet DBM, Wright Medical Technology, Inc) have been evaluated preclinically in a bilateral medullary defect model of a canine humerus. In this model, both short (6 week) and long (26 week) time points have been evaluated. An analysis of bone response to the pellets was conducted using radiological, histological, mechanical, and quantification techniques. The calcium sulfate/DBM pellets exhibited more rapid trabecular bone remodeling as demonstrated by the absence of the ringlet bone structure typically seen with calcium sulfate pellets. We concluded that calcium sulfate and calcium sulfate/DBM pellets are both effective bone graft substitutes.

The use of acellular dermal matrix as a scaffold for periosteum replacement.

Three preclinical models were used to evaluate GraftJacket Acellular Periosteum Replacement Scaffold (Wright Medical Technology, Inc, Arlington, Tenn). The studies assessed the ability of the acellular dermal matrix to repopulate with cells, revascularize, provide a protected environment for bone defect restoration, and minimize fibrous tissue infiltration. An athymic nude rat muscle implantation study demonstrated a steady increase in cellular repopulation through days 2-21. The formation of blood vessels occurred between days 7-14 in this study. Results from a porcine femoral drill hole study indicated that the scaffold material was intact and adherent to surrounding bone and allowed cellular repopulation and vascular infiltration at a 5-week time period. A preliminary porcine segmental bone defect model at a 6-week time period demonstrated the ability of the scaffold material to protect the bone defect site as revealed by new bone formation within the margins of the defect and adjacent to the scaffold. The segmental model also indicated minimal to no soft tissue invasion into the defect site. The combined studies provided preliminary evidence that the dermal membrane material may be used as a scaffold for periosteum regeneration by allowing for cellular repopulation, revascularization, and bone defect restoration.