Transgenic overexpression of CTRP3 does not prevent alcohol induced hepatic steatosis in female mice.

Alcoholic liver disease (ALD) is one of the leading causes of morbidity and mortality from hepatic complications. C1q/TNF-related protein 3 (CTRP3) is an adiponectin paralog and, in male mice, increased levels of circulating CTRP3 prevents ALD. Therefore, the purpose of this study was to replicate the observed hepatoprotective effect of elevated circulating CTRP3 levels in female mice. Twelve-week-old female wildtype and CTRP3 overexpressing transgenic mice were fed the Lieber-DeCarli alcohol-containing liquid diet (5% vol/vol) for 6 weeks. Unlike the previous study with male mice, CTRP3 overexpression provided no attenuation to alcohol-induced hepatic lipid accumulation, cytokine production, or overall mortality. In conclusion, there appears to be a clear sex-specific effect of CTRP3 in response to alcohol consumption that needs to be explored further.

A global reconnaissance of particulates and metals/metalloids in untreated drinking water sources.

Metal and metalloid contamination in drinking water sources is a global concern, particularly in developing countries. This study used hollow membrane water filters and metal-capturing polyurethane foams to sample 71 drinking water sources in 22 different countries. Field sampling was performed with sampling kits prepared in the lab at Hope College in Holland, MI, USA. Filters and foams were sent back to the lab after sampling, and subsequent analysis of flushates and rinsates allowed the estimation of suspended solids and metal and other analayte concentrations in source waters. Estimated particulate concentrations were 0-92 mg/L, and consisted of quartz, feldspar, and clay, with some samples containing metal oxides or sulfide phases. As and Cu were the only analytes which occurred above the World Health Organization (WHO) guidelines of 10 µg/L and 2000 µg/L, respectively, with As exceeding the guideline in 45% of the sources and Cu in 3%. Except for one value of ~ 285 µg/L, As concentrations were 45-200 µg/L (river), 65-179 µg/L (well), and 112-178 µg/L (tap). Other metals (Ce, Fe, Mg, Mn, Zn) with no WHO guideline were also detected, with Mn the most common. This study demonstrated that filters and foams can be used for reconnaissance characterization of untreated drinking water. However, estimated metal and other analyte concentrations could only be reported as minimum values due to potential incomplete retrieval of foam-bound analytes. A qualitative reporting methodology was used to report analytes as "present" if the concentration was below the WHO guideline, and "present-recommend retesting" if the concentration was quantifiable and above the WHO guideline.

Three-dimensional Printing in Orthopaedic Surgery: Current Applications and Future Developments.

Three-dimensional (3D) printing is an exciting form of manufacturing technology that has transformed the way we can treat various medical pathologies. Also known as additive manufacturing, 3D printing fuses materials together in a layer-by-layer fashion to construct a final 3D product. This technology allows flexibility in the design process and enables efficient production of both off-the-shelf and personalized medical products that accommodate patient needs better than traditional manufacturing processes. In the field of orthopaedic surgery, 3D printing implants and instrumentation can be used to address a variety of pathologies that would otherwise be challenging to manage with products made from traditional subtractive manufacturing. Furthermore, 3D bioprinting has significantly impacted bone and cartilage restoration procedures and has the potential to completely transform how we treat patients with debilitating musculoskeletal injuries. Although costs can be high, as technology advances, the economics of 3D printing will improve, especially as the benefits of this technology have clearly been demonstrated in both orthopaedic surgery and medicine as a whole. This review outlines the basics of 3D printing technology and its current applications in orthopaedic surgery and ends with a brief summary of 3D bioprinting and its potential future impact.

Diarrhea prevalence in a randomized, controlled prospective trial of point-of-use water filters in homes and schools in the Dominican Republic.

BACKGROUND: Lack of sustainable access to clean drinking water continues to be an issue of paramount global importance, leading to millions of preventable deaths annually. Best practices for providing sustainable access to clean drinking water, however, remain unclear. Widespread installation of low-cost, in-home, point of use water filtration systems is a promising strategy. METHODS: We conducted a prospective, randomized, controlled trial whereby 16 villages were selected and randomly assigned to one of four treatment arms based on the installation location of Sawyer® PointONE™ filters (filter in both home and school; filter in home only; filter in school only; control group). Water samples and self-reported information on diarrhea were collected at multiple times throughout the study. RESULTS: Self-reported household prevalence of diarrhea decreased from 25.6 to 9.76% from installation to follow-up (at least 7 days, and up to 200 days post-filter installation). These declines were also observed in diarrhea with economic or educational consequences (diarrhea which led to medical treatment and/or missing school or work) with baseline prevalence of 9.64% declining to 1.57%. Decreases in diarrhea prevalence were observed across age groups. There was no evidence of a loss of efficacy of filters up to 200 days post-filter installation. Installation of filters in schools was not associated with decreases in diarrhea prevalence in school-aged children or family members. Unfiltered water samples both at schools and homes contained potential waterborne bacterial pathogens, dissolved heavy metals and metals associated with particulates. All dissolved metals were detected at levels below World Health Organization action guidelines. CONCLUSIONS: This controlled trial provides strong evidence of the effectiveness of point-of-use, hollow fiber membrane filters at reducing diarrhea from bacterial sources up to 200 days post-installation when installed in homes. No statistically significant reduction in diarrhea was found when filters were installed in schools. Further research is needed in order to explore filter efficacy and utilization after 200 days post-installation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03972618 . Registered 3 June 2019-retrospectively registered.

Does Surgeon Subspecialty Training Affect Outcomes in the Treatment of Displaced Supracondylar Humerus Fractures in Children?

INTRODUCTION: The effect of the treating surgeon's subspecialty training on the outcomes of managing displaced supracondylar humerus fractures in the pediatric cohort remains under debate. The objective of this study was to examine patient outcomes and treatment variables for these injuries based on the surgeon subspecialty training. METHODS: A retrospective study of children who had undergone primary closed reduction and percutaneous fixation for displaced supracondylar humerus fractures was done from January 2012 through May 2019. The following four groups with differing orthopaedic subspecialty training were evaluated: (1) pediatric fellowship trained (2) trauma fellowship trained, (3) sports medicine fellowship trained, and (4) all others. Outcomes examined included time to surgery, surgical time, fluoroscopy usage, postoperative follow-up protocols, radiographic measurements of alignment, and complications between surgeon groups. RESULTS: Two hundred thirty-one cases were included (mean age 6 ± 2 years). Pediatric fellowship-trained surgeons took patients to surgery in a more delayed fashion (>12 hours, P = 0.02). Surgical time and fluoroscopy usage were significantly shorter for pediatric fellowship-trained surgeons (P < 0.001). No statistical difference was noted in pin configuration constructs between the groups. Pediatric fellowship-trained surgeons, on average, saw patients two times postoperatively within a year with most patients being within 30 days. Complications were not statistically different between the groups. CONCLUSIONS: Pediatric fellowship-trained orthopaedic surgeons provide more efficient care on a more delayed basis for displaced supracondylar humerus fractures than other subspecialty-trained orthopaedic surgeons. However, if barriers exist that limit the practicality or availability of these specialists, nonpediatric fellowship-trained surgeons achieve similar and satisfactory outcomes. LEVEL OF EVIDENCE: Level III retrospective cohort study.

Bark beetles as lidar targets and prospects of photonic surveillance.

Forestry is raising concern about the outbreaks of European spruce bark beetle, Ips typographus, causing extensive damage to the spruce forest and timber values. Precise monitoring of these beetles is a necessary step towards preventing outbreaks. Current commercial monitoring methods are catch-based and lack in both temporal and spatial resolution. In this work, light scattering from beetles is characterized, and the feasibility of entomological lidar as a tool for long-term monitoring of bark beetles is explored. Laboratory optical properties, wing thickness, and wingbeat frequency of bark beetles are reported, and these parameters can infer target identity in lidar data. Lidar results from a Swedish forest with controlled bark beetle release event are presented. The capability of lidar to simultaneously monitor both insects and a pheromone plume mixed with chemical smoke governing the dispersal of many insects is demonstrated. In conclusion, entomological lidar is a promising tool for monitoring bark beetles.

CTRP3 and serum triglycerides in children aged 7-10 years.

INTRODUCTION: The prevalence of obesity-related disorders has been steadily increasing over the past couple of decades. Diseases that were once only detected in adults are now prevalent in children, such as hyperlipidemia. The adipose tissue-derived hormonal factor C1q TNF Related Protein 3 (CTRP3) has been linked to triglyceride regulation especially in animal models. However, the relationship between circulating CTRP3 levels and obesity-related disorders in human subjects is controversial. CTRP3 can circulate in different oligomeric complexes: trimeric (<100 kDa), middle molecular weight (100-300 kDa), and high molecular weight (HMW) oligomeric complexes (>300 kDa). Previous work has identified that it is not the total amount of CTRP3 present in the serum, but the specific circulating oligomeric complexes that appear to be indicative of the relationship between CTRP3 and serum lipids levels. However, this work has not been examined in children. Therefore, the purpose of this study was to compare the levels of different oligomeric complexes of CTRP3 and circulating lipid levels among young children (aged 7-10 years). METHODS: Morphometric data and serum samples were collected and analyzed from a cross-sectional population of 62 children of self-identified Hispanic origin from a community health center, between 2015 and 2016. Serum analysis included adiponectin, insulin, leptin, ghrelin, glucagon, C-reactive peptide, triglyceride, cholesterol, IL-6, TNF, and CTRP3. Correlation analyses were conducted to explore the relationships between CTRP3 and other biomarkers. RESULTS: Total CTRP3 concentrations were significantly positively correlated with total cholesterol and HDL cholesterol. Whereas, HMW CTRP3 was not significantly associated with any variable measured. Conversely, the middle molecular weight (MMW) CTRP3 was negatively correlated with triglycerides levels, and very low-density lipoprotein (VLDL), insulin, and body mass index (BMI). The negative correlations between MMW CTRP3 and triglycerides and VLDLs were particularly strong (r2 = -0.826 and -0.827, respectively). CONCLUSION: Overall, these data indicate that the circulating oligomeric state of CTRP3 and not just total CTRP3 level is important for understanding the association between CTRP3 and metabolic diseases. Further, this work indicates that MMW CTRP3 plays an important role in triglyceride and VLDL regulation which requires further study.

High-fat diet induces fibrosis in mice lacking CYP2A5 and PPARα: a new model for steatohepatitis-associated fibrosis.

Obesity is linked to nonalcoholic steatohepatitis. Peroxisome proliferator-activated receptor-α (PPARα) regulates lipid metabolism. Cytochrome P-450 2A5 (CYP2A5) is a potential antioxidant and CYP2A5 induction by ethanol is CYP2E1 dependent. High-fat diet (HFD)-induced obesity and steatosis are more severe in CYP2A5 knockout (cyp2a5-/-) mice than in wild-type mice although PPARα is elevated in cyp2a5-/- mice. To examine why the upregulated PPARα failed to prevent the enhanced steatosis in cyp2a5-/- mice, we abrogate the upregulated PPARα in cyp2a5-/- mice by cross-breeding cyp2a5-/- mice with PPARα knockout (pparα-/-) mice to create pparα-/-/cyp2a5-/- mice. The pparα-/-/cyp2a5-/- mice, pparα-/- mice, and cyp2a5-/- mice were fed HFD to induce steatosis. After HFD feeding, more severe steatosis was developed in pparα-/-/cyp2a5-/- mice than in pparα-/- mice and cyp2a5-/- mice. The pparα-/-/cyp2a5-/- mice and pparα-/- mice exhibited comparable and impaired lipid metabolism. Elevated serum alanine transaminase and liver interleukin-1ß, liver inflammatory cell infiltration, and foci of hepatocellular ballooning were observed in pparα-/-/cyp2a5-/- mice but not in pparα-/- mice and cyp2a5-/- mice. In pparα-/-/cyp2a5-/- mice, although redox-sensitive transcription factor nuclear factor erythroid 2-related factor 2 and its target antioxidant genes were upregulated as a compensation, thioredoxin was suppressed, and phosphorylation of JNK and formation of nitrotyrosine adduct were increased. Liver glutathione was decreased, and lipid peroxidation was increased. Interestingly, inflammation and fibrosis were all observed within the clusters of lipid droplets, and these lipid droplet clusters were all located inside the area with CYP2E1-positive staining. These results suggest that HFD-induced fibrosis in pparα-/-/cyp2a5-/- mice is associated with steatosis, and CYP2A5 interacts with PPARα to participate in regulating steatohepatitis-associated fibrosis.

Circulating levels of CTRP3 in patients with type 2 diabetes mellitus compared to controls: A systematic review and meta-analysis.

Growing evidence suggests that adipokines may be therapeutic targets for cardiometabolic diseases such as type 2 diabetes mellitus (T2DM). C1q TNF Related Protein 3 (CTRP3) is a newly discovered adipokine which shares properties with adiponectin. The literature about the association between circulating levels of CTRP3 and T2DM has been conflicting. The present study reassessed the data on circulating CTRP3 levels in T2DM patients compared to controls through a systematic review and meta-analysis. A literature search was performed in Medline, Embase, Scopus, and Web of science to identify studies that measured circulating CTRP3 levels in T2DM patients and controls. The search identified 124 studies of which 59 were screened for title and abstract and 13 were subsequently screened at the full text stage and 12 studies included into the meta-analysis. Subgroup analyses, depending on the presence of T2DM complications, matching for BMI, age, and cut off value of fasting blood sugar and HOMA-IR, were performed. The results show that circulating CTRP3 levels are negatively associated with T2DM status (SMD: -0.837; 95% CI: (-1.656 to -0.017); p = 0.045). No publication bias was identified using the Begg's rank correlation and Egger's linear regression tests (P = 1 and P = 0.44, respectively). Meta-regression demonstrated significant association between CRTP3 levels with BMI (slope: 0.11; 95% CI: 0.04-0.19; p = 0.001) and sex (slope: -0.07; 95% CI: -0.12 to -0.01; p = 0.008). The present systematic review and meta-analysis evidences a negative association between circulating level of CTRP3 and T2DM status. BMI and sex may modify this association.

Surgeon-Performed High-Dose Bupivacaine Periarticular Injection With Intra-Articular Saphenous Nerve Block Is Not Inferior to Adductor Canal Block in Total Knee Arthroplasty.

BACKGROUND: Periarticular injection or anesthesiologist-performed adductor canal block are commonly used for pain management after total knee arthroplasty. A surgeon-performed, intra-articular saphenous nerve block has been recently described. There is insufficient data comparing the efficacy and safety of these methods. METHODS: This is a retrospective two-surgeon cohort study comparing short-term perioperative outcomes after primary total knee arthroplasty, in 50 consecutive patients with surgeon-performed high-dose periarticular injection and intra-articular saphenous nerve block (60 mL 0.5% bupivacaine, 30 mL saline, 30mg ketorolac) and 50 consecutive patients with anesthesiologist-performed adductor canal catheter (0.25% bupivacaine 6 mL/h infusion pump placed postoperatively with ultrasound guidance). Chart review assessed pain scores through POD #1, opioid use, length of stay, and short-term complications, including local anesthetic systemic toxicity. Statistical analysis was performed with two-tailed Student's T-test. RESULTS: The high-dose periarticular injection cohort had significantly lower pain scores in the postanesthesia care unit (mean difference 1.4, P = .035), on arrival to the inpatient ward (mean difference 1.7, P = .013), and required less IV narcotics on the day of surgery (mean difference 6.5 MME, P = .0004). There was no significant difference in pain scores on POD #1, total opioid use, day of discharge, or short-term complications. There were no adverse events related to the high dose of bupivacaine. CONCLUSION: Compared with postoperative adductor canal block catheter, an intraoperative high-dose periarticular block demonstrated lower pain scores and less IV narcotic use on the day of surgery. No difference was noted in pain scores on POD #1, time to discharge, or complications. There were no cardiovascular complications (local anesthetic systemic toxicity) despite the high dose of bupivacaine injected. LEVEL OF EVIDENCE: III.

Antibiotic Cement Spacers for Infected Total Knee Arthroplasties.

Periprosthetic infection remains a frequent complication after total knee arthroplasty. The most common treatment is a two-stage procedure involving removal of all implants and cement, thorough débridement, insertion of some type of antibiotic spacer, and a course of antibiotic therapy of varying lengths. After some interval, and presumed eradication of the infection, new arthroplasty components are implanted in the second procedure. These knee spacers may be static or mobile spacers, with the latter presumably providing improved function for the patient and greater ease of surgical reimplantation. Numerous types of antibiotic cement spacers are available, including premolded cement components, surgical molds for intraoperative spacer fabrication, and the use of new metal and polyethylene knee components; all these are implanted with surgeon-prepared high-dose antibiotic cement. As there are advantages and disadvantages of both static and the various mobile spacers, surgeons should be familiar with several techniques. There is inconclusive data on the superiority of any antibiotic spacer. Both mechanical complications and postoperative renal failure may be associated with high-dose antibiotic cement spacers.

High molecular weight, but not total, CTRP3 levels are associated with serum triglyceride levels.

C1q/TNF-related protein 3 (CTRP3) is a relatively novel adipose tissue-derived cytokine (adipokine) which has been linked to improved glucose regulation and insulin sensitivity. However, the relationship between circulating CTRP3 levels and diabetes is controversial. CTRP3 can circulate in different oligomeric complexes: trimeric, hexameric, and high molecular weight (HMW) oligomeric complexes. However, the concentration of the different oligomeric complexes in human disease states has not been previously investigated. Therefore, the purpose of this study was to compare the levels of different oligomeric complexes of CTRP3 between type 2 diabetic and nondiabetic individuals. Additionally, the association between the oligomeric complexes and other serum factors was examined. CTRP3 primarily circulates in the HMW complex (>50%) and the hexametric multimer, with no CTRP3 detected in the trimeric complex or as a monomer. Further, no differences were observed in total, hexameric, or HMW CTRP3 levels regardless of diabetic status. Surprisingly, HMW CTRP3 was found to be positively correlated with circulating triglyceride levels. Combined, these data suggest that CTRP3 is associated with triglyceride regulation, not diabetic status. These data may explain some of the discrepancies in the literature as elevated triglyceride levels are often detected in patients with obesity and type 2 diabetes.

Muscle regulates mTOR dependent axonal local translation in motor neurons via CTRP3 secretion: implications for a neuromuscular disorder, spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder, which causes dysfunction/loss of lower motor neurons and muscle weakness as well as atrophy. While SMA is primarily considered as a motor neuron disease, recent data suggests that survival motor neuron (SMN) deficiency in muscle causes intrinsic defects. We systematically profiled secreted proteins from control and SMN deficient muscle cells with two combined metabolic labeling methods and mass spectrometry. From the screening, we found lower levels of C1q/TNF-related protein 3 (CTRP3) in the SMA muscle secretome and confirmed that CTRP3 levels are indeed reduced in muscle tissues and serum of an SMA mouse model. We identified that CTRP3 regulates neuronal protein synthesis including SMN via mTOR pathway. Furthermore, CTRP3 enhances axonal outgrowth and protein synthesis rate, which are well-known impaired processes in SMA motor neurons. Our data revealed a new molecular mechanism by which muscles regulate the physiology of motor neurons via secreted molecules. Dysregulation of this mechanism contributes to the pathophysiology of SMA.

Bilateral tibial tubercle avulsion fractures: A pediatric orthopedic injury at high risk for compartment syndrome.

Adolescent tibial tubercle avulsion fractures represent an uncommon, but clinically significant condition for emergency medicine physicians. Early recognition of the signs and symptoms of this pediatric orthopedic diagnosis are important, as anterior compartment syndrome can occur in up to 10-20% of cases. Anterior tibial tubercle fractures are generally sport related injuries, occurring primarily in otherwise healthy adolescent males between the ages of 11-17. They account for less than 3% of all epiphyseal injuries in this age group and are rarely bilateral in nature. In this article, we present a case with two unique clinical features: bilateral sports related tibial tubercle avulsion fractures and subsequent development of bilateral clinical compartment syndrome. We briefly review the risk factors, presentation, and diagnosis of this rare but clinically important condition.

Fracture of the neck of an uncemented femoral component unrelated to trunnion corrosion.

This is the first report, to our knowledge, of a fracture, unrelated to trunnion corrosion, through the midneck of a well-fixed uncemented cobalt-chromium alloy femoral component that had been implanted via a total hip revision arthroplasty 25 years ago. Three years after a second revision for polyethylene wear, the patient noted an acute onset of pain in the left hip. There was no antecedent pain in the hip or thigh. Radiographs and intraoperative findings showed a well-fixed femoral component. Electron microscopic retrieval analysis showed intergranular material cracks. Revision of the femoral component was performed with an extended trochanteric osteotomy. This fracture of the femoral component neck was likely related to metal fabrication techniques, and surveillance of this component may be warranted.

Coordinating Tissue Regeneration Through Transforming Growth Factor-ß Activated Kinase 1 Inactivation and Reactivation.

Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of transforming growth factor-ß activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by reactivation to elicit differentiation and extracellular matrix production. Although the current regenerative medicine paradigm is centered on the effects of drug treatment ("drug on"), the impact of drug withdrawal ("drug off") implicit in these regimens is unknown. Because current TAK1 inhibitors are unable to phenocopy genetic Tak1 loss, we introduce the dual-inducible COmbinational Sequential Inversion ENgineering (COSIEN) mouse model. The COSIEN mouse model, which allows us to study the response to targeted drug treatment ("drug on") and subsequent withdrawal ("drug off") through genetic modification, was used here to inactivate and reactivate Tak1 with the purpose of augmenting tissue regeneration in a calvarial defect model. Our study reveals the importance of both the "drug on" (Cre-mediated inactivation) and "drug off" (Flp-mediated reactivation) states during regenerative therapy using a mouse model with broad utility to study targeted therapies for disease. Stem Cells 2019;37:766-778.

Exogenous ubiquitin reduces inflammatory response and preserves myocardial function 3 days post-ischemia-reperfusion injury.

ß-Adrenergic receptor (ß-AR) stimulation increases extracellular levels of ubiquitin (UB) in myocytes, and exogenous UB decreases ß-AR-stimulated myocyte apoptosis and myocardial fibrosis. Here, we hypothesized that exogenous UB modulates the inflammatory response, thereby playing a protective role in cardiac remodeling after ischemia-reperfusion (I/R) injury. C57BL/6 mice infused with vehicle or UB (1 µg·g-1·h-1) were subjected to myocardial I/R injury. Functional and biochemical parameters of the heart were examined 3 days post-I/R. Heart weight-to-body weight ratios were similarly increased in I/R and UB + I/R groups. The area at risk and infarct size were significantly lower in UB + I/R versus I/R groups. Measurement of heart function using echocardiography revealed that I/R decreases percent fractional shortening and percent ejection fraction. However, the decrease in fractional shortening and ejection fraction was significantly lower in the UB + I/R group. The UB + I/R group displayed a significant decrease in inflammatory infiltrates, neutrophils, and macrophages versus the I/R group. Neutrophil activity was significantly lower in the UB + I/R group. Analysis of the concentration of a panel of 23 cytokines/chemokines in the serum using a Bio-Plex assay revealed a significantly lower concentration of IL-12 subunit p40 in the UB + I/R versus I/R group. The concentration of monocyte chemotactic protein-1 was lower, whereas the concentration of macrophage inflammatory protein-1α was significantly higher, in the UB+I/R group versus the sham group. Expression of matrix metalloproteinase (MMP)-2 and activity of MMP-9 were higher in the UB + I/R group versus the I/R group. Levels of ubiquitinated proteins and tissue inhibitor of metalloproteinase 2 expression were increased to a similar extent in both I/R groups. Thus, exogenous UB plays a protective role in myocardial remodeling post-I/R with effects on cardiac function, area at risk/infarct size, the inflammatory response, levels of serum cytokines/chemokines, and MMP expression and activity. NEW & NOTEWORTHY Stimulation of ß-adrenergic receptors increases extracellular levels of ubiquitin (UB) in myocytes, and exogenous UB decreases ß-adrenergic receptor-stimulated myocyte apoptosis and myocardial fibrosis. Here, we provide evidence that exogenous UB decreases the inflammatory response and preserves heart function 3 days after myocardial ischemia-reperfusion injury. Further identification of the molecular events involved in the anti-inflammatory role of exogenous UB may provide therapeutic targets for patients with ischemic heart disease.

The Use of Bone Grafts, Bone Graft Substitutes, and Orthobiologics for Osseous Healing in Foot and Ankle Surgery.

Achieving fusion in osseous procedures about the foot and ankle presents unique challenges to the surgeon. Many patients have comorbidities that reduce osseous healing rates, and the limited space and high weightbearing demand placed on fusion sites makes the choice of bone graft, bone graft substitute, or orthobiologic agent of utmost importance. In this review, we discuss the essential characteristics of grafts, including their osteoconductive, osteoinductive, osteogenic, and angiogenic properties. Autologous bone graft remains the gold standard and contains all these properties. However, the convenience and lack of donor site morbidity of synthetic bone grafts, allografts, and orthobiologics, including growth factors and allogenic stem cells, has led to these being used commonly as augments. LEVEL OF EVIDENCE: Level V, expert opinion.