Biomedical subjects

Samantha L Salkeld

Publications and source records attributed to Samantha L Salkeld.

8 recordsLinked to original sources

PubMed2005

Bone defect healing with an osteogenic protein-1 device combined with carboxymethylcellulose.

One consideration for the practical use and application of osteogenic proteins is an effective method of delivery. This study evaluated a putty-type collagen carrier with recombinant human osteogenic protein-1 (rhOP-1) ability to heal canine critical sized (2.5 cm) ulna segmental defects compared to rhOP-1 with a particulate collagen carrier (OP device). The addition of carboxymethylcellulose (CMC) to the particulate collagen carrier (OPCMC device) to form the putty consistency was evaluated in two doses (3.5 and 1.75 mg rhOP-1/g carrier). The CMC greatly improved the intraoperative handling and site containment of the device. For the one-half dose and full-dose sites there were no statistically significant differences in the radiographic grading of defect healing when treated with the particulate OP-1 device and the device with CMC added. However, there was a dose effect with greater and earlier new bone formation observed with increased rhOP-1. Mechanically, there were no differences between particulate and putty formulations, although again, a significant effect was observed for treatment dose with the full-dose OPCMC device restoring 94% of the strength of the intact ulna compared to only 65% for the identical one-half dose implant. Regardless of rhOP-1 dose, the quality of union grading and total histologic score appearance were improved with the addition of CMC, although differences in histologic scoring were not statistically significant. Overall, the radiographic, mechanical, and histologic bone-healing characteristics with the one-half dose OPCMC device were similar to sites treated with the full-dose OP device. The observed improvement in healing may allow for lesser amounts of the device or a device with less rhOP-1 to be used.

Animals↗

PubMed2004

Osteogenic protein-1 in knee arthritis and arthroplasty.

The use of graft materials to restore bone stock and promote healing and implant stabilization is a crucial part of total knee arthroplasty, especially in revision surgery. Recent research has centered on the use of osteoinductive materials to promote bone formation. Osteogenic proteins are members of a superfamily of proteins called transforming growth factor-beta that, either alone or in combination with other regulatory molecules, induce new bone formation. The cloning and genetic expression of recombinant human osteogenic proteins has led to production of quantities sufficient for their clinical use. Recombinant human osteogenic protein-1 has been combined with bone-derived Type I collagen for delivery to an implant site. Preclinical studies have shown that the osteoinductive capacity of autograft and allograft bone and bone graft substitute materials can be notably improved with the addition of osteogenic protein-1. The use of this protein consistently improved the amount and rate of new bone formation compared with graft alone, resulting in earlier graft incorporation and consolidation. In addition, because osteogenic proteins are chondrogenic, they also may have a role in the treatment of cartilage injury and degeneration. Osteogenic protein-1 has been shown to induce hyalinelike cartilage repair of full thickness osteochondral defects in animal models with no degradation of the tissue with time. Although no detailed clinical studies in knee surgery have been reported with the use of osteogenic protein-1, in anecdotal cases its use alone and with bone graft materials indicate results consistent with those obtained in preclinical studies.

Arthroplasty, Replacement, Knee↗

PubMed2003

Induction of bone ingrowth from acetabular defects to a porous surface with OP-1.

Reliable ingrowth of bone into porous-coated cementless total hip components can be expected in primary surgery. In the revision scenario, however, bone deficiency frequently is encountered and the remaining bone may have less ingrowth potential. Allograft bone and bone graft substitutes may be successful in healing bone defects, but have virtually no capacity to induce bone growth from the defect into the porous surface. To evaluate the role osteoinductive bone proteins may play in enhancing bone ingrowth, six canines had bilateral total hip arthroplasties with a cementless press-fit porous-coated acetabular component. A defect 8 mm in diameter and 5 mm in depth was created in the superior weightbearing area of each acetabulum. One defect in each animal was filled with recombinant human osteogenic protein-1. Each contralateral defect was filled with allograft bone, left empty (defect healing control), or no defect was created (intact) to serve as a control for ideal conditions for bone ingrowth. The osteogenic protein-treated defects healed more completely than allograft bone-treated or empty defects and achieved a bone density equivalent to the intact acetabulum. Bone ingrowth also occurred to a significantly higher degree in the osteogenic protein group compared with the allograft or empty defects achieving a degree of ingrowth equivalent to the intact acetabulum controls. The osteogenic bone protein was successful in achieving complete defect healing and inducing extensive ingrowth from the defect into the adjacent porous coating.

Acetabulum↗

PubMed2003

Osteoinductive agents in reconstructive hip surgery: a look forward.

The use of autograft and allograft material to restore bone stock and promote healing and implant stabilization is a crucial part of total hip arthroplasty, especially in the revision situation. Recent research has centered on the use of osteoinductive materials such as osteogenic proteins or bone morphogenetic proteins to promote bone formation. These proteins are members of the transforming growth factor-beta superfamily of proteins that either alone or in combination with other regulatory molecules induce new bone formation. The cloning and genetic expression of recombinant human bone proteins has led to production of quantities sufficient for their clinical development. Preclinical studies have shown that the osteoinductive capacity of autograft and allograft bone can be improved with the addition of osteogenic proteins. Although these proteins are effective alone, their use with cancellous and cortical allograft and autograft consistently improved the amount and rate of new bone formation compared with graft alone resulting in earlier graft incorporation and consolidation. When placed in defects adjacent to porous acetabular components, the use of an osteogenic protein resulted in earlier defect healing and improved component fixation by the enhancement of bone ongrowth and ingrowth. Although no detailed clinical studies have been reported to date, an anecdotal report of their use with and without bone graft indicate results consistent with those obtained in preclinical studies.

Arthroplasty, Replacement, Hip↗

PubMed2003

Repair of articular cartilage defects with osteogenic protein-1 (BMP-7) in dogs.

BACKGROUND: Articular cartilage injury has a poor prognosis for repair. Mesenchymal cells, when exposed to osteogenic proteins and other cytokines, can differentiate into cells that behave phenotypically as chondrocytes. In this study, we examined the ability of recombinant human osteogenic protein-1 (rhOP-1 or rhBMP-7) to elicit the repair of osteochondral defects in dogs. METHODS: Bilateral osteochondral defects that were 5 mm in diameter by 6 mm deep were surgically created in the medial femoral condyles of sixty-five adult dogs. rhOP-1-treated (100 mg of a 3.5-mg rhOP-1/g bovine bone-derived Type-I collagen device) and control defects (untreated or treated with 100 mg bovine bone-derived collagen implants) were evaluated grossly and histologically at six, twelve, sixteen, twenty-six, and fifty-two weeks postoperatively. The influence of protected initial weight-bearing and surgical placement of periosteal flaps was also evaluated. RESULTS: Gross and histologic grading of the defect repair indicated improvement in the rhOP-1-treated defects compared with that in the controls. Grossly, the repair tissue in the rhOP-1-treated defects was continuous with the adjacent intact cartilage and appeared translucent. By comparison, the repair tissue in the control defects was discontinuous and opaque or inhomogeneous in nature. Histologically, maturing cartilage similar in appearance to the intact articular cartilage was present in the rhOP-1-treated defects. Cartilage at the defect interface was minimally degraded. The control defects were filled primarily with fibrous tissue and fibrocartilage. Significant differences based upon treatment type were observed at twelve weeks, sixteen weeks, and for all time-periods combined (p = 0.0385, p = 0.0070, and p = 0.0026, respectively). CONCLUSION: rhOP-1 (rhBMP-7) induced hyaline cartilage-like repair of full-thickness osteochondral defects in a dog model. Differences in cartilage repair were maintained at fifty-two weeks postoperatively with no significant degradation of the rhOP-1-induced repair tissue.

Animals↗

PubMed2002

The effect of demineralized bone matrix gel on bone ingrowth and fixation of porous implants.

The presence of demineralized bone matrix (DBM) gel did not enhance or accelerate attachment strength or bone ingrowth and resulted in a significant decrease in implant interface attachment strength at 3 weeks. Hydroxyapatite (HA) coating resulted in significant increases in interface shear strength and bone ingrowth compared with non-HA-coated porous implants at all time periods. The HA-coated implants achieved greater attachment strength and bone ingrowth at earlier time periods and maintained greater attachment strength at long-term periods. The results of this study indicate that in the presence of a good bone-implant interference fit, there is no beneficial effect in applying DBM gel to a porous-coated or HA-coated porous implant surface. The small amount that can be applied and the degree of osteoinductivity of DBM seem to preclude it from having a significant biologic effect.

Animals↗

PubMedDate not supplied

Biomechanical study of pedicle screw fixation in severely osteoporotic bone.

BACKGROUND CONTEXT: Obtaining adequate purchase with standard pedicle screw techniques remains a challenge in poor quality bone. The development of alternate insertion techniques and screw designs was prompted by recognition of potential fixation complications. An expandable pedicle screw design has been shown to significantly improve fixation compared to a conventional screw in poor quality bone. PURPOSE: The purpose of this study was to determine if polymethylmethacrylate (PMMA) bone cement augmentation of an expandable pedicle screw can further improve fixation strength compared to the expandable screw alone in severely osteoporotic bone. A technique for cement insertion into the pedicle by means of the cannulated central portion of the expandable screw is also described. STUDY DESIGN: The axial pullout strength, stiffness and energy absorbed of cemented and noncemented expandable pedicle screws was determined in cadaveric vertebrae. METHODS: Twenty-one fresh unembalmed vertebrae from the thoracolumbar spine were used. Radiographs and bone mineral density measurements (BMD) were used to characterize bone quality. Paired cemented and noncemented pedicle screw axial pullout strength was determined through mechanical testing. Mechanical pullout strength, stiffness and energy to failure was correlated with BMD. RESULTS: Overall, there was a 250% increase in mean pullout strength with the cemented expandable screw compared with a noncemented expandable screw including a greater than twofold increase in pullout strength in the most severely osteoporotic bone. The mean stiffness and energy absorbed to failure was also significantly increased. A cemented conventional screw achieved a pullout strength similar to the noncemented expandable screw. CONCLUSIONS: PMMA cement augmentation of the expandable pedicle screw may be a viable clinical option for achieving fixation in severely osteoporotic bone.

Aged↗

PubMedDate not supplied

Healing course of primate ulna segmental defects treated with osteogenic protein-1.

Twelve African green monkeys were implanted with recombinant human osteogenic protein-1 (rhOP-1) placed on a bovine bone-derived Type I collagen carrier to characterize healing in an ulna segmental bone defect model at 1, 3, 12, and 20 weeks postoperative. Defect healing was evaluated by plain film radiography, computed tomography (CT), magnetic resonance imaging (MRI), bone mineral density (BMD), and histologic analysis. Radiographically, new bone formation was observed as early as 3 weeks postoperative. By 6 weeks, new bone was visible in five of six defects. Increased quantity and mineralization of the new bone were apparent by 12 weeks. Reformation of the medullary cavity with appearance of marrow elements was demonstrated by CT and MRI at 20 weeks. BMD studies revealed a significant increase in the presence of bone with time. Histology at 1 week demonstrated that the implant material was well contained in the defect, and a proliferation of cells occurred at the defect borders. At 3 weeks cell proliferation continued and cell phenotype differentiation was recognized. By 12 weeks substantially less residual carrier was found in the defects, and calcifying tissues with plump chondrocytes, osteoblasts, and immature woven bone were observed. Areas of lamellar and woven bone were identified at 12 weeks, with advanced remodeling and revascularization observed at 20 weeks. The use of osteoinductive implants may provide an alternative to autologous and allogeneic bone tissue in the therapeutic approach to bone defects and promotion of fusion by eliminating the donor site morbidity associated with autogenous bone and the decreased efficacy and potential for disease transmission associated with allogeneic bone.

Animals↗