Nondestructive, longitudinal measurement of collagen scaffold degradation using computed tomography and gold nanoparticles.

Biodegradable materials, such as collagen scaffolds, are used extensively in clinical medicine for tissue regeneration and/or as an implantable drug delivery vehicle. However, available methods to study biomaterial degradation are typically invasive, destructive, and/or non-volumetric. Therefore, the objective of this study was to investigate a new method for nondestructive, longitudinal, and volumetric measurement of collagen scaffold degradation. Gold nanoparticles (Au NPs) were covalently conjugated to collagen fibrils during scaffold preparation to enable contrast-enhanced imaging of collagen scaffolds. The X-ray attenuation of as-prepared scaffolds increased linearly with increased Au NP concentration such that ≥60 mM Au NPs provided sufficient contrast to measure scaffold degradation. Collagen scaffold degradation kinetics were measured to increase during in vitro enzymatic degradation in media with an increased concentration of collagenase. The scaffold degradation kinetics measured by micro-CT exhibited lower variability compared with gravimetric measurement and were validated by measurement of the release of Au NPs from the same samples by optical spectroscopy. Thus, Au NPs and CT synergistically enabled nondestructive, longitudinal, and volumetric measurement of collagen scaffold degradation.

Micrometer-Sized Magnesium Whitlockite Crystals in Micropetrosis of Bisphosphonate-Exposed Human Alveolar Bone.

Osteocytes are contained within spaces called lacunae and play a central role in bone remodelling. Administered frequently to prevent osteoporotic fractures, antiresorptive agents such as bisphosphonates suppress osteocyte apoptosis and may be localized within osteocyte lacunae. Bisphosphonates also reduce osteoclast viability and thereby hinder the repair of damaged tissue. Osteocyte lacunae contribute to toughening mechanisms. Following osteocyte apoptosis, the lacunar space undergoes mineralization, termed "micropetrosis". Hypermineralized lacunae are believed to increase bone fragility. Using nanoanalytical electron microscopy with complementary spectroscopic and crystallographic experiments, postapoptotic mineralization of osteocyte lacunae in bisphosphonate-exposed human bone was investigated. We report an unprecedented presence of ∼80 nm to ∼3 µm wide, distinctly faceted, magnesium whitlockite [Ca18Mg2(HPO4)2(PO4)12] crystals and consequently altered local nanomechanical properties. These findings have broad implications on the role of therapeutic agents in driving biomineralization and shed new insights into a possible relationship between bisphosphonate exposure, availability of intracellular magnesium, and pathological calcification inside lacunae.

Osseointegration of a 3D Printed Stemmed Titanium Dental Implant: A Pilot Study.

In this pilot study, a 3D printed Grade V titanium dental implant with a novel dual-stemmed design was investigated for its biocompatibility in vivo. Both dual-stemmed (n = 12) and conventional stainless steel conical (n = 4) implants were inserted into the tibial metaphysis of New Zealand white rabbits for 3 and 12 weeks and then retrieved with the surrounding bone, fixed, dehydrated, and embedded into epoxy resin. The implants were analyzed using correlative histology, microcomputed tomography, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The histological presence of multinucleated osteoclasts and cuboidal osteoblasts revealed active bone remodeling in the stemmed implant starting at 3 weeks and by 12 weeks in the conventional implant. Bone-implant contact values indicated that the stemmed implants supported bone growth along the implant from the coronal crest at both 3- and 12-week time periods and showed bone growth into microporosities of the 3D printed surface after 12 weeks. In some cases, new bone formation was noted in between the stems of the device. Conventional implants showed mechanical interlocking but did have indications of stress cracking and bone debris. This study demonstrates the comparable biocompatibility of these 3D printed stemmed implants in rabbits up to 12 weeks.

Baseline comorbidities and treatment strategy in elderly patients are associated with outcome of cardiogenic shock in a community-based population.

BACKGROUND: Cardiogenic shock (CGS) historically results in high inhospital mortality, particularly in elderly patients. Factors that contribute to increased mortality and treatment strategies that improve short- and long-term outcomes in patients with CGS remain to be established. METHODS: The study consisted of 1263 consecutive patients with acute myocardial infarction admitted from Olmsted County, Minn, during the period 1988 to 2000; of these, 73 (6%) developed cardiogenic shock. Short- and long-term mortality was compared between the elderly and younger populations in both shock and nonshock groups. RESULTS: In patients with acute myocardial infarction, age of > or =65 years was associated with increased long-term mortality for nonshock patients (unadjusted relative risk [RR] 5.23, 95% CI 4.10-6.67, P <.001) and to a lesser degree in patients with cardiogenic shock (unadjusted RR 2.02, 95% CI 1.12-3.65, P =.02). Among cardiogenic shock patients, estimated survival at 1 and 5 years for elderly patients was 38% and 24%, respectively, and in younger patients, 57% and 52%, respectively. When adjusted for confounding variables, elderly noncardiogenic shock patients had significantly increased long-term mortality (adjusted RR 4.38, 95% CI 3.42-5.61, P <.001) compared to younger nonshock patients. In contrast, elderly patients with cardiogenic shock demonstrated a weaker trend toward worse outcomes (adjusted RR 1.80, 95% CI 1.00-3.27, P =.051) compared to younger patients with shock. CONCLUSIONS: The relationship between age and long-term mortality is stronger among patients who do not develop cardiogenic shock. Advanced age was not found to be as strong a risk factor for survival in patients with cardiogenic shock; comorbidities and less aggressive treatment appear to be the major factors resulting in poor outcomes in the elderly patient with cardiogenic shock.

Effect of diabetes on the mortality risk of cardiogenic shock in a community-based population.

OBJECTIVE: To examine the mortality of diabetic vs nondiabetic patients with anterior myocardial infarction (AMI) among the subsets of this population who did and did not develop cardiogenic shock. PATIENTS AND METHODS: The study population consisted of a consecutive series of 1263 Olmsted County, Minnesota, patients admitted to the coronary care unit at the Mayo Clinic in Rochester, Minn, between January 1, 1988, and July 31, 2000. Of these patients, 73 met the criteria for cardiogenic shock during their hospitalization. In-hospital and postadmission mortality were compared between diabetic and nondiabetic patients within the cardiogenic shock and nonshock patient groups, respectively. RESULTS: In patients with AMI and cardiogenic shock, diabetes was associated with a trend for increased in-hospital mortality (odds ratio, 2.82; 95% confidence interval [CI], 0.90-9.92; P = .08). In 73 patients with cardiogenic shock, estimated survival at 1, 3, and 5 years was 25%, 17%, and 17%, respectively, for diabetic patients, and 50%, 44%, and 36%, respectively, for nondiabetic patients (P = .046). The association between diabetic patients and increased long-term mortality was stronger in patients with cardiogenic shock than in patients without cardiogenic shock (adjusted relative risk, 2.08; 95% CI, 1.11-3.90; P = .02). In diabetic patients without cardiogenic shock, estimated survival at 1, 3, and 5 years was low, at 75%, 61%, and 45%, respectively, compared with 83%, 76%, and 69%, respectively, for nondiabetic patients (adjusted relative risk, 1.29; 95% CI, 1.02-1.62; P = .03). CONCLUSION: The presence of diabetes as a comorbidity in patients with AMI appears to be associated with increased mortality compared with nondiabetic patients, and this relationship may be potentially magnified in patients who develop cardiogenic shock.