The implant material hydroxylapatite (HA) has been shown in numerous studies to be highly biocompatible and to osseointegrate well with existing bone; however, the molecular mechanisms at work behind this osseointegration remain largely unexplored. One possibility is that the implant, exposed to the patient's blood during surgery, adsorbs known cell adhesive proteins such as fibronectin and vitronectin from the serum. Osteoblast precursors could then adhere to these proteins through integrin-mediated mechanisms. In the present study, we have used a quantitative ELISA assay to test the hypothesis that hydroxylapatite will adsorb more fibronectin and vitronectin from serum than two commonly used hard-tissue materials, commercially pure titanium, and 316L stainless steel. We further used the ELISA, as well as a standard cell adhesion assay, to test the hypothesis that increased protein adsorption will lead to better binding of purified integrins alpha5beta1 and alpha(v)beta3 and osteoblast precursor cells to the HA than to the metals. Our results show that fibronectin, vitronectin, alpha5beta1, alpha(v)beta3, and osteoblast precursor cells do indeed bind better to HA than to the metals, suggesting that improved integrin-mediated cell binding may be one of the mechanisms leading to better clinical bone integration with HA-coated implants.
Due to an editing error, there was some misinformation relayed in the Abstract of the article by Kilpadi et al., Primary human marrow stromal cells and Saos-2 osteosarcoma cells use different mechanisms to adhere to hydroxylapatite, which was published in Volume 68A, Issue 2, pages 273-285, of the journal.The publisher apologizes for this error and offers, in its entirety, the corrected abstract, presented below.Abstract: One important step in bone formation on hard tissue implants is adhesion of osteoblast precursors to the implant surface. In this study, we used function-blocking antibodies against integrin subunits to characterize the mechanisms used by human marrow stromal cells and Saos-2 osteosarcoma cells to adhere to protein-coated hydroxylapatite (HA). We found that Saos-2 use both ␣ 5 -and ␣ v -containing integrins, whereas stromal cells use ␣ v -containing integrins but not ␣ 5 -containing integrins, despite the presence of ␣ 5 -containing integrins on cell surfaces. On the basis of this difference, we examined binding of these cell types to HA coated with fibronectin (FN) or vitronectin (VN), to determine whether these ligands for ␣ 5 and ␣ v integrins could enhance the numbers or morphology of cells adhered to them. We also examined the adhesion of cells to HA coated with RGD peptides designed to bind to FN or VN receptors. Morphology and number of adherent stromal cells were markedly enhanced on serum-coated surfaces compared with FN or VN alone, whereas, surprisingly, Saos-2 cells failed to spread on serum-coated HA and displayed superior spreading and stress fiber formation on FN-coated HA. Collectively, these results have important implications for the design of protein coatings to enhance the performance of HA implants.
The aim of this study was to determine if split-thickness skin grafts could be successfully used for closure of foot and ankle wounds in diabetic patients. The authors retrospectively reviewed the charts of 100 consecutive patients who underwent a soft tissue surgical reconstruction with split-thickness skin grafts to their foot and/or ankle in our institution from 2005 to 2008. After application of inclusion criteria, 83 eligible charts remained. Of the 83 patients, 54 (65%) healed uneventfully, 23 (28%) required regrafting, and 6 (7%) had a complication resolved with conservative management. All patients had a successful surgical outcome, defined as having achieved complete wound closure at the final follow-up. Surgical outcome was not significantly associated with age, gender, race, hemoglobin A1C, wound size, wound location, illicit drug use, amputation history, Charcot history, or preoperative infection. However, postoperative graft complications were significantly associated with current or previous smoking history (P = .016) and the level of previous pedal amputation to which the split-thickness skin graft was applied (P = .009). This study demonstrates that application of split-thickness skin grafts with an appropriate postoperative regimen is a beneficial procedure to achieve foot and ankle wound closure in diabetic patients.
For individuals with diabetes but without exclusionary comorbidities, split-thickness skin grafting may be considered an effective surgical alternative to other prolonged treatment options currently used in this patient population.
One important step in bone formation on hard tissue implants is adhesion of osteoblast precursors to the implant surface. In this study, we used function-blocking antibodies against integrin subunits to characterize the mechanisms used by human marrow stromal cells and Saos-2 osteosarcoma cells to adhere to protein-coated hydroxylapatite (HA). We found that Saos-2 use both alpha5- and alphav-containing integrins, whereas stromal cells use alphav-containing integrins but not alpha5-containing integrins, despite the presence of alpha5-containing integrins on cell surfaces. On the basis of this difference, we examined binding of these cell types to HA coated with fibronectin (FN) or vitronectin (VN), to determine whether these ligands for alpha5 and alphav integrins could enhance the numbers or morphology of cells adhered to them. We also examined the adhesion of cells to HA coated with RGD peptides designed to bind to FN or VN receptors. Morphology and number of adherent stromal cells were markedly enhanced on serum-coated surfaces compared with FN or VN alone, whereas, surprisingly, Saos-2 cells failed to spread on serum-coated HA and displayed superior spreading and stress fiber formation on FN-coated [corrected] HA. Collectively, these results have important implications for the design of protein coatings to enhance the performance of HA implants.
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