Efficacy of sintered Zinc-doped fluorapatite scaffold as an antimicrobial regenerative bone filler for dental applications.

OBJECTIVES: The objective of this study was to assess whether zinc-doped fluorapatite (ZnFA) could serve as an effective antimicrobial dental bone filler for bone regeneration compared to autografts. METHODS: FA and 2 % zinc-doped FA (2ZnFA) were synthesized and characterized in-house. Compressed and sintered FA and 2ZnFA disks were incubated with bacteria to assess antimicrobial properties. Adipose-derived stem cells were cultured on these discs to evaluate the surfaces' ability to support cell growth and promote osteogenic differentiation. Surfaces exhibiting the highest expressions of the bone markers osteopontin and osteocalcin were selected for an in vivo study in a rat mandibular defect model. Twenty rats were divided into 5 groups, equally, and a 5 mm surgical defect of the jaw was left untreated or filled with 2ZnFA, FA, autograft, or demineralized bone matrix (DBM). At 12 weeks, the defects and surrounding tissues were harvested and subjected to microCT and histological evaluations. RESULTS: Standard techniques such as FTIR, ICP-MS, fluoride probe, and XRD revealed the sintered FA and ZnFA's chemical compositions and structures. Bacterial studies revealed no significant differences in surface bacterial adhesion properties between FA and 2ZnFA, but significantly fewer bacterial loads than control titanium discs (p < 0.05). Cell culture data confirmed that both surfaces could support cell growth and promote the osteogenic differentiation of stem cells. MicroCT analysis confirmed statistical similarities in bone regeneration within FA, 2ZnFA, and autograft groups. CONCLUSION: The data suggests that both FA and 2ZnFA could serve as alternatives to autograft materials, which are the current gold standard. Moreover, these bone fillers outperformed DBM, an allograft material commonly used as a dental bone void filler. CLINICAL SIGNIFICANCE: The use of FA or 2ZnFA for treating mandibular defects led to bone regeneration statistically similar to autograft repair and significantly outperformed the widely used dental bone filler, DBM. Additional translational research may confirm FA-based materials as superior substitutes for existing synthetic bone fillers, ultimately enhancing patient outcomes.

Association between blood markers and the progression of osseointegration in percutaneous prostheses patients-A pilot study.

Patients implanted with osseointegrated (OI) prosthetic systems have reported vastly improved upper and lower extremity prosthetic function compared with their previous experience with socket-suspension systems. However, OI systems have been associated with superficial and deep-bone infections and implant loosening due, in part, to a failure of the osseointegration process. Although monitoring the osseointegration using circulating biomarkers has clinical relevance for understanding the progression of osseointegration with these devices, it has yet to be established. Ten patients were enrolled in this study. Blood samples were collected at pre-selected times, starting before implantation surgery, and continuing to 12 months after the second surgery. Bone formation markers, bone resorption markers, and circulating amino acids were measured from blood samples. A linear mixed model was generated for each marker, incorporating patient ID and age with the normalized marker value as the response variable. Post hoc comparisons were made between 1 week before Stage 1 Surgery and all subsequent time points for each marker, followed by multiple testing corrections. Serial radiographic imaging of the residual limb containing the implant was obtained during follow-up, and the cortical index (CI) was calculated for the bone at the porous region of the device. Two markers of bone formation, specifically bone-specific alkaline phosphatase (Bone-ALP) and amino-terminal propeptide of type I procollagen (PINP), exhibited significant increases when compared with the baseline levels of unloaded residual bone prior to the initial surgery, and they subsequently returned to their baseline levels by the 12-month mark. Patients who experienced clinically robust osseointegration experienced increased cortical bone thickness at the porous coated region of the device. A medium correlation was observed between Bone-ALP and the porous CI values up to PoS2-M1 (p = .056), while no correlation was observed for PINP. An increase in bone formation markers and the lack of change observed in bone resorption markers likely reflect increased cortical bone formation induced by the end-loading design of the Utah OI device used in this study. A more extensive study is required to validate the correlation observed between Bone-ALP and porous CI values.

Dental implant failures in Utah and US veteran cohorts.

INTRODUCTION: Approximately, 5.5 million dental implants are estimated to be surgically placed in the United States yearly, with an anticipated long-term failure rate ranging from 3% to 10%. At the Salt Lake City Dental Clinic within the Department of Veterans Affairs (VHA), specific protocols have been established to mandate that clinicians present every dental implant case for review by a committee. To understand the effectiveness of this approach, a comparative data analysis was undertaken to compare local dental implant failure data against national VHA data. METHODS: Leveraging electronic health records of veterans spanning from 2000 to 2021, we gathered procedural records related to dental implant placement or failure, demographic information, and medical history for individuals who received dental care at various dental clinics within the nationwide VHA network. Subsequently, statistical analyses were conducted using mixed-effects Poisson regression models with cluster-robust standard errors. Incident rate ratios (IRRs) for Utah-specific and nationwide cohorts were ascertained. RESULTS: The Utah VHA dental clinical data showed that there was a slightly lower prevalence of implant failure at 6.7% compared to the national cohort, which had a rate of 6.9%. The implant level failure rates were also low, with 4.20 (confidence interval [CI]: 3.68, 4.81) per 1000 implant placements per year for Utah cohorts. The adjusted IRR indicated a relative 16% reduction in risk among Utah Veterans (IRR 0.84, 95% CI [0.76-0.92]; p < 0.001). CONCLUSIONS: The stringent protocols in place at Salt Lake City, which integrate evidence-based practices and expert opinion for evaluating patient suitability for dental implant placement and subsequent care, contributed to the reduced risk among Utah Dental Clinic veterans pool compared to veterans of other states.

Sintered fluorapatite scaffolds as an autograft-like engineered bone graft.

Hydroxyapatite (HA)-based materials are widely used as bone substitutes due to their inherent biocompatibility, osteoconductivity, and bio-absorption properties. However, HA scaffolds lack compressive strength when compared to autograft bone. It has been shown that the fluoridated form of HA, fluorapatite (FA), can be sintered to obtain this desired strength as well as slower degradation properties. Also, FA surfaces have been previously shown to promote stem cell differentiation toward an osteogenic lineage. Thus, it was hypothesized that FA, with and without stromal vascular fraction (SVF), would guide bone healing to an equal or better extent than the clinical gold standard. The regenerative potentials of these scaffolds were tested in 32 Lewis rats in a femoral condylar defect model with untreated (negative), isograft (positive), and commercial HA as controls. Animals were survived for 12 weeks post-implantation. A semi-quantitative micro-CT analysis was developed to quantify the percent new bone formation within the defects. Our model showed significantly higher (p < .05) new bone depositions in all apatite groups compared to the autograft group. Overall, the FA group had the most significant new bone deposition, while the differences between HA, FA, and FA + SVF were insignificant (p > .05). Histological observations supported the micro-CT findings and highlighted the presence of healthy bone tissues without interposing capsules or intense immune responses for FA groups. Most importantly, the regenerating bone tissue within the FA + SVF scaffolds resembled the architecture of the surrounding trabecular bone, showing intertrabecular spaces, while the FA group presented a denser cortical bone-like architecture. Also, a lower density of cells was observed near FA granules compared to HA surfaces, suggesting a reduced immune response. This first in vivo rat study supported the tested hypothesis, illustrating the utility of FA as a bone scaffold material.

Freeze casting of hydroxyapatite-titania composites for bone substitutes.

Hydroxyapatite (HA) is commonly used as a bone substitute material, but it lacks mechanical strength when compared to native bone tissues. To improve the efficacy of HA as a bone substitute by improving the mechanical strength and cell growth attributes, porous composite scaffolds of HA and titania (HA-TiO2 ) were fabricated through a freeze-casting process. Three different compositions by weight percent, 25-75 HA-TiO2 , 50-50 HA-TiO2 , and 75-25 HA-TiO2 , were custom-made for testing. After sintering at 1250°C, these composite scaffolds exhibited improved mechanical properties compared to porous HA scaffolds. Substrate mixing was observed, which helped reduce crystal size and introduced new phases such as ß-TCP and CaTiO3 , which also led to improved mechanical properties. The composition of 50-50 HA-TiO2 had the highest ultimate compressive strength of 3.12 ± 0.36 MPa and elastic modulus 63.29 ± 28.75 MPa. Human osteoblast cell proliferation assay also increased on all three different compositions when compared to porous HA at 14 days. These results highlight the potential of freeze casting composites for the fabrication of bone substitutes, which provide enhanced mechanical strength and biocompatibility while maintaining porosity.

Serum procalcitonin level is independently associated with mechanical ventilation and case-fatality in hospitalized COVID-19-positive US veterans-A potential marker for disease severity.

The Coronavirus-19 disease (COVID-19) has claimed over 6.8 million lives since first being reported in late 2019. The virus that causes COVID-19 disease is highly contagious and spreads rapidly. To date, there are no approved prognostic tools that could predict why some patients develop severe or fatal disease outcomes. Early COVID-19 studies found an association between procalcitonin (PCT) and hospitalization or duration of mechanical ventilation and death but were limited by the cohort sizes. Therefore, this study was designed to confirm the associations of PCT with COVID-19 disease severity outcomes in a large cohort. For this retrospective data analysis study, 27,154 COVID-19-positive US veterans with post-infection PCT laboratory test data and their disease severity outcomes were accessed using the VA electronic healthcare data. Cox regression models were used to test the association between serum PCT levels and disease outcomes while controlling for demographics and relevant confounding variables. The models demonstrated increasing disease severity (ventilation and death) with increasing PCT levels. For PCT serum levels above 0.20 ng/ml, the unadjusted risk increased nearly 2.3-fold for mechanical ventilation (hazard ratio, HR, 2.26, 95%CI: 2.11-2.42) and in-hospital death (HR, 2.28, 95%CI: 2.16-2.41). Even when adjusted for demographics, diabetes, pneumonia, antibiotic use, white blood cell count, and serum C-reactive protein levels, the risks remained relatively high for mechanical ventilation (HR, 1.80, 95%CI: 1.67-1.94) and death (HR, 1.76, 95%CI: 1.66-1.87). These data suggest that higher PCT levels have independent associations with ventilation and in-hospital death in veterans with COVID-19 disease, validating previous findings. The data suggested that serum PCT level may be a promising prognostic tool for COVID-19 severity assessment and should be further evaluated in a prospective clinical trial.

A Dentist's Perspective on the Need for Interdisciplinary Collaboration to Reduce Medication-Related Osteonecrosis of the Jaw.

Antiresorptive medications, including bisphosphonates and RANK-L inhibitors, are commonly used to treat various skeletal pathologies. One devastating complication associated with these drugs is medication-related osteonecrosis of the jaw (MRONJ). Patients who develop MRONJ suffer immensely from oral lesions that may persist, even with treatment, until their death. The jawbone is known to remodel 5 to 10 times faster than skeletal bone. Dentists are at the forefront in managing the severe maxillofacial repercussions of MRONJ. Because MRONJ risk is relatively low (reportedly 0.7% to 6.7%) it is underappreciated by many clinical specialties. The minimization of MRONJ is further compounded because it may take months or years to develop. To date, dental treatment protocols are based more on expert opinion than concrete scientific evidence. This iatrogenic, intractable illness is discouraging for both the patient and the treating dentist. To promote multidisciplinary understanding and cooperation, a single MRONJ case caused by intravenous pamidronate is presented, along with commentary from a dentist's perspective. The intent is that these data will increase awareness of MRONJ's stomatognathic consequences to the physician, who prescribed the causative agent, and the pharmacist, who dispensed it. Collaboration between the dentist, physician, and pharmacist has tremendous potential to improve treatment strategies and, ultimately, optimize patient care.

A preliminary, observational study using whole-blood RNA sequencing reveals differential expression of inflammatory and bone markers post-implantation of percutaneous osseointegrated prostheses.

AIMS: While the benefits of direct skeletal attachment of artificial limbs are well recognized, device failure due to infection and insufficient osseointegration remain obstacles to obtaining consistently successful outcomes. Currently, the potential for device failure is assessed by subjective pain, clinical function scores, radiographic evidence of bone atrophy, and the presence of radiolucent lines at the bone-implant interface, and subjective pain and function scores. Our hypothesis is that measurable biological indices might add another objective means to assess trends toward bone and stomal healing. This longitudinal cohort study was undertaken to identify potential serological biomarkers suggestive of bone remodeling and the presence of stomal tissue inflammation. METHODS: Ten unilateral transfemoral amputee veterans, who were implanted with a percutaneous osseointegrated (OI) skeletal limb docking system, were recruited to participate in this IRB-approved study. Venous blood samples were obtained from before the Stage 1 Surgery up to 1 year following the Stage 2 Surgery. Whole-blood RNA was extracted, sequenced, mapped, and analyzed. Of the significant differentially expressed (DEGs) genes (p<0.05) identified, four genes of interest (IL12B, IL33, COL2A1, and SOST) were validated using qPCR. Enrichment analysis was performed to identify significant (p<0.01) Gene Ontology (GO) terms. RESULTS: Most differentially expressed genes were only detected at PoS1 immediately after the first surgery. Of the significant genes identified, IL12B and IL33 were related to inflammation, and COL2A1 and SOST were associated with bone remodeling. These four genes were identified with greater than 20 log fold-change. CONCLUSION: Whole-blood RNA-seq data from 10 patients who previously underwent percutaneous osseointegrated lower limb implantation revealed four genes of interest that are known to be involved in inflammation or bone remodeling. If verified in future studies, these genes may serve as markers for predicting optimal bone remodeling and stomal tissue healing following OI device implantation.

Hospitalization, mechanical ventilation, and case-fatality outcomes in US veterans with COVID-19 disease between years 2020-2021.

PURPOSE: Although veterans represent a significant proportion (7%) of the USA population, the COVID-19 disease impact within this group has been underreported. To bridge this gap, this study was undertaken. METHOD: A total of 419,559 veterans, who tested positive for COVID-19 disease in the Veterans Affairs hospital system from March 1st, 2020 to December 31st, 2021 with 60-days follow-up, was included in this retrospective review. Primary outcome measures included age-adjusted incidences and relative incidences of COVID-19 hospitalization, mechanical ventilation, and case-fatality outcomes. RESULTS: Of this veteran cohort with COVID-19 disease, predominately 85.7% were male, 59.1% were White veterans, 27.5% were ages 50-64, and 40.5% were obese. Although Black veterans were at 63% higher relative risk (RR) for hospitalization incidences, they had a similar risk RR for in-hospital deaths compared to the White-veteran referent. Asian, American Indian/Alaska Native races, advanced age ≥65, and the underweight were at high RR for mechanical ventilator and/or in-hospital deaths compared to respective referent groups. Veterans who are ≥85 years old had a nearly 5-fold higher incidence of death compared respective referent group. The monthly outcomes for hospitalization, ventilation, and case-fatality data showed decreasing trends with time. CONCLUSION: An increased incidence of death was associated with age ≥65 years and underweight veterans compared to the referent group. Age-adjusted data, however, did not show any increased incidence of death in Black veterans compared to White veterans. RATINGS OF THE QUALITY OF THE EVIDENCE: 3 (Case-control studies; retrospective cohort study).

Fluorapatite and fluorohydroxyapatite apatite surfaces drive adipose-derived stem cells to an osteogenic lineage.

PURPOSE: Hydroxyapatite (HA) scaffolds are common replacement materials used in the clinical management of critical-sized bone defects. This study was undertaken to examine the potential benefits of fluoridated derivatives of hydroxyapatite, fluorapatite (FA), and fluorohydroxyapatite (FHA) as bone scaffolds in conjunction with adipose-derived stem cells (ADSCs). If FHA and FA surfaces could drive the differentiation of stem cells to an osteogenic phenotype, the combination of these ceramic scaffolds with ADSCs could produce materials with mechanical strength and remodeling potential comparable to autologous bone. This study was designed to investigate the ability of the apatite surfaces HA, FA, and FHA produced at different sintering temperatures to drive ADSCs toward osteogenic lineages. METHODS: HA, FHA, and FA surfaces sintered at 1150 °C and 1250 °C were seeded with ADSCs and evaluated for cell growth and gene and protein expression of osteogenic markers at 2 and 10 days post-seeding. RESULTS: In vitro, ADSC cells were viable on all surfaces; however, differentiation of these cells into osteoblastic lineage only observed in apatite surfaces. ADSCs seeded on FA and FHA expressed genes and proteins related to osteogenic differentiation markers to a greater extent by Day 2 when compared to HA and cell culture controls. By day 10, HA, FA, and FHA all expressed more bone differentiation markers compared to cell culture controls. CONCLUSION: FA and FHA apatite scaffolds may promote the differentiation of ADSCs at an earlier time point than HA surfaces. Combining apatite scaffolds with ADSCs has the potential to improve bone regeneration following bone injury.

Characterization of porous fluorohydroxyapatite bone-scaffolds fabricated using freeze casting.

With the increasing demand for orthopedic and dental reconstruction surgeries, there comes a shortage of viable bone substitutes. This study was therefore designed to assess the efficacy of porous fluorohydroxyapatite (FHA) as a potential bone substitute. For this, porous FHA scaffolds were fabricated using the freeze casting technique. They were then sintered at 1250, 1350 and, 1450 °C, and microstructural, mechanical, and in vitro properties were analyzed. The microstructure analyses revealed the porosity remained constant within the temperature range. However, the pore size decreased with increasing sintering temperature. The greatest compressive strength and elastic modulus were obtained at 1450 °C, which were 13.5 ± 4.0 MPa and 379 ± 182 MPa, respectively. These are comparable values to human trabecular bone and other porous scaffolds made using hydroxyapatite. This analysis has thus helped to attain an understanding of the mechanical and material properties of freeze-cast FHA scaffolds that have not been presented before. In vitro studies revealed an increasing rate of human osteoblast cell proliferation on freeze-cast FHA scaffolds with increasing sintering temperature, suggesting improved osteogenic properties. Additionally, osteoblasts cells were also shown to proliferate into the interior pores of all freeze-cast FHA scaffolds. These results indicate the potential of porous FHA scaffolds fabricated using the freeze-casting technique to be utilized clinically as bone substitutes.

Coronavirus disease 2019 in veterans receiving care at veterans health administration facilities.

PURPOSE: Veterans represent a significant proportion of the U.S. population (7%), and the impact of the coronavirus disease 2019 (COVID-19) in this group of vulnerable patients has been largely overlooked. This analysis reports COVID-19 patient demographics, infection, mortality, and case-fatality rates in the veteran population. METHODS: This is a cross-sectional analysis using the Veterans Affairs informatics and computing infrastructure tool to assess the veterans' COVID-19 infections at the Veterans Affairs facilities from March 4th to June 23rd, 2020. RESULTS: Of the 10,621,580 veterans in this analysis, 59.7% were ≥65 yo, 92.5% were men, 68.7% were white, and 14.2% were black. Veterans ≥65 yo comprised 52.1% of cases and 89.9% of deaths. The relative mortality and case-fatality rates of black veterans, when compared with white veterans, were 2.83 (CI 2.56-3.14; P < .001) and 0.75 (CI 0.68-0.82; P < .001), respectively. Among the veterans who died from COVID-19, 87.4% had a history of cardiovascular disease, 56.5% had a history of diabetes, and 33.6% were obese. CONCLUSIONS: Elderly veterans (≥65yo) and veterans with a history of cardiovascular disease represent a large proportion of the VA COVID-19 cases and deaths. Black veterans had higher mortality rates but lower case fatality rates when than white veterans.

Evaluation of soft-tissue response around laser microgrooved titanium percutaneous devices.

Percutaneous devices are prone to epidermal downgrowth and sinus tract formation, which can serve as a nidus for bacterial colonization and increase the risk of peri-prosthetic infection. A laser microgrooved topography has been shown to limit gingival epidermal downgrowth around dental implants. However, the efficacy of this laser microgrooved topography to limit epidermal downgrowth around nongingival percutaneous devices is yet to be investigated. In this study, devices with a porous-coated subdermal component and a percutaneous post were designed and manufactured. The proximal 2 mm section of the percutaneous post were left smooth, or were textured with either a porous coating, or with the laser microgrooved topography. The smooth and porous topographies served as controls. The devices were tested in a hairless guinea pig back model, where 18 animals were randomly assigned into three groups, with each group receiving one implant type (n = 6/group). Four weeks postimplantation, the devices with surrounding soft-tissues were harvested and processed for histological analyses. Results indicated that the laser microgrooved topography failed to prevent epidermal downgrowth (23 ± 4%) around percutaneous posts in this model. Furthermore, no significant differences (p = 0.70) in epidermal downgrowth were present between the three topographies, with all the groups exhibiting similar measures of downgrowth. Overall, these findings suggest that the laser microgrooved topography may not halt downgrowth around percutaneous devices for dermal applications.

Epidermal growth factor receptor genes are overexpressed within the periprosthetic soft-tissue around percutaneous devices: A pilot study.

Epidermal downgrowth around percutaneous devices produce sinus tracts, which then accumulate bacteria becoming foci of infection. This mode to failure is epidermal-centric, and is accelerated by changes in the chemokines and cytokines of the underlying periprosthetic granulation tissue (GT). In order to more fully comprehend the mechanism of downgrowth, in this 28-day study, percutaneous devices were placed in 10 Zucker diabetic fatty rats; 5 animals were induced with diabetes mellitus II (DM II) prior to the surgery and 5 animals served as a healthy, nondiabetic cohort. At necropsy, periprosthetic tissues were harvested, and underwent histological and polymerase chain reaction (PCR) studies. After isolating GTs from the surrounding tissue and extracting ribonucleic acids, PCR array and quantitative-PCR (qPCR) analyses were carried-out. The PCR array for 84 key wound-healing associated genes showed a five-fold or greater change in 31 genes in the GTs of healthy animals compared to uninjured healthy typical skin tissues. Eighteen genes were overexpressed and these included epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR). Thirteen genes were underexpressed. When GTs of DM II animals were compared to healthy animals, there were 8 genes overexpressed and 25 genes underexpressed; under expressed genes included EGF and EGFR. The qPCR and immunohistochemistry data further validated these observations. Pathway analysis of genes up-regulated 15-fold or more indicated two, EGFR and interleukin-10, centric clustering effects. It was concluded that EGFR could be a key player in exacerbating the epidermal downgrowth, and might be an effective target for preventing downgrowth.

Variation in bone response to the placement of percutaneous osseointegrated endoprostheses: A 24-month follow-up in sheep.

Percutaneous osseointegrated (OI) devices for amputees are metallic endoprostheses, that are surgically implanted into the residual stump bone and protrude through the skin, allowing attachment of an exoprosthetic limb. In contrast to standard socket suspension systems, these percutaneous OI devices provide superior attachment platforms for artificial limbs. However, bone adaptation, which includes atrophy and/or hypertrophy along the extent of the host bone-endoprosthetic interface, is seen clinically and depends upon where along the bone the device ultimately transfers loading forces to the skeletal system. The goal of this study was to determine if a percutaneous OI device, designed with a porous coated distal region and an end-loading collar, could promote and maintain stable bone attachment. A total of eight, 18 to 24-month old, mixed-breed sheep were surgically implanted with a percutaneous OI device. For 24-months, the animals were allowed to bear weight as tolerated and were monitored for signs of bone remodelling. At necropsy, the endoprosthesis and the surrounding tissues were harvested, radiographically imaged, and histomorphometrically analyzed to determine the periprosthetic bone adaptation in five animals. Bone growth into the porous coating was achieved in all five animals. Serial radiographic data showed stress-shielding related bone adaptation occurs based on the placement of the endoprosthetic stem. When collar placement and achieved end-bearing against the transected bone, distal bone conservation/hypertrophy was observed. The results supported the use of a distally loading and distally porous coated percutaneous OI device to achieve distal host bone maintenance.

Analysis of the Stomal Microbiota of a Percutaneous Osseointegrated Prosthesis: A Longitudinal Prospective Cohort Study.

Percutaneous osseointegrated (OI) prostheses (POPs) are used to skeletally attach artificial limbs in amputees. While any permanent percutaneous interface is at risk of becoming infected by the resident microbiota colonizing the stoma, most of these patients remain infection-free. Avoidance of infection likely depends upon a mechanically and/or biologically stable skin-to-implant interface. The ultimate question remains, "why do some stomata become infected while others do not?" The answer might be found in the dynamic bacterial communities of the patient and within the stomal site itself. This study is an appendix to the first Food and Drug Administration approved prospective early feasibility study of OI prosthetic docking, in which, 10 transfemoral amputees were implanted with a unique POP device. In this analytical, longitudinal cohort study, each patient's skin and stomal microbiota were analyzed from the initial surgery to 1 year following the second-stage surgery. During each follow-up visit, three swab samples-stomal, device thigh skin and contralateral thigh skin-were obtained. DNA was extracted, and bacterial 16S ribosomal RNA (rRNA) genes were amplified and sequenced to profile microbial communities. The stomal microbiota were distinct from the microbiota on the adjacent thigh skin and the skin of the contralateral thigh, with a significantly increased abundance of Staphylococcus aureus within the stoma. Early on stomal microbiota were characterized by high diversity and high relative abundance of obligate anaerobes. Over time, the stomal microbiota shifted and stabilized in communities of lower diversity dominated by Streptococcus, Corynebacterium, and/or Staphylococcus spp. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2645-2654, 2019.

Biomimetic coatings and negative pressure wound therapy independently limit epithelial downgrowth around percutaneous devices.

Biomimetic material coatings and negative pressure wound therapy (NPWT) have been shown independently to limit the epithelial downgrowth rates in percutaneous devices. It was therefore hypothesized that these techniques, in combination, could further limit the clinically observed epithelial downgrowth around these devices. In this study, we evaluated the efficacy of two biomimetic coatings, collagen and hydroxyapatite (HA), to prevent downgrowth when used with continuous NPWT. Using an established single-stage surgical protocol, collagen (n = 10) and HA (n = 10) coated devices were implanted subdermally on the back of hairless guinea pigs. Five animals from each group were subjected to continuous ~90 mmHg NPWT. Four weeks post-implantation, animals were sacrificed, and the devices and surrounding tissues were harvested, processed, and downgrowth was computed and compared to historical porous titanium coated controls. Data showed a significant reduction in downgrowth in NPWT treated animals (p ≤ 0.05) when compared to the untreated porous titanium controls. HA coated devices, without the NPWT treatment, also showed significantly decreased downgrowth compared to the untreated porous titanium controls.

Characterization and evaluation of fluoridated apatites for the development of infection-free percutaneous devices.

The wound healing process in the soft tissues adjacent to percutaneous implants induces "epithelial downgrowth", and subsequently, a sinus tract around the device. This provides an optimal environment for bacterial colonization and proliferation. In an attempt to arrest downgrowth and achieve epithelial attachment to a device surface, we have sought to mimic the most common and successful percutaneous organ, the tooth. Since teeth are composed of partially and fully fluoridated forms of hydroxyapatite (HA), it was hypothesized that the surface properties of fluoridated apatites, fluorohydroxyapatite (FHA) and fluorapatite (FA), would improve epithelial cellular adhesion and differentiation when compared to HA and titanium (Ti) surfaces. In this study, the apatites (HA, FHA, and FA) were synthesized and characterized. Following a high-temperature sintering treatment of these apatites, keratinocyte and fibroblast adhesion and differentiation properties were analyzed in vitro, revealing a statistically significant increase in keratinocyte adhesion and terminal differentiation on FA surfaces sintered at 1050-1150 °C as compared to Ti or HA. Moreover, fibroblasts displayed enhanced adhesion on FHA surfaces. This data suggests that percutaneous devices coated with, or fabricated from, fluoridated apatites may induce improved epithelial cellular adhesion and differentiation, potentially limiting deeply penetrating epithelial downgrowth and resultant bacterial ingress.

Influence of negative pressure wound therapy on peri-prosthetic tissue vascularization and inflammation around porous titanium percutaneous devices.

Negative Pressure Wound Therapy (NPWT) has been shown to limit downgrowth around percutaneous devices in a guinea pig model. However, the influence of NPWT on peri-prosthetic tissue characteristics leading to limited downgrowth is still unclear. In order to investigate this, 12 CD hairless rats were assigned into two groups, NPWT and Untreated (n = 6/group). Each animal was implanted with a porous coated titanium percutaneous device and was dressed with a gauze and semi-occlusive base dressing. Post-surgery, animals in the NPWT Group received a regimen of NPWT treatment (-70 to -90 mmHg). After 4 weeks, tissue was collected over the device and stained with CD31 and CD68 to quantify blood vessel density and inflammation, respectively. The device with the surrounding tissue was also collected to quantify downgrowth. NPWT treatment led to a 1.6-fold increase in blood vessel densities compared to untreated tissues (p < 0.05). NPWT treatment also resulted in half the downgrowth as the Untreated Group, although not statistically significant (p = 0.19). Additionally, the results showed a trend toward increased CD68 cell densities in the NPWT Group compared to the Untreated Group (p = 0.09). These findings suggest that NPWT may influence wound healing responses in percutaneous devices by increasing blood vessel densities, limiting downgrowth and potentially increasing inflammation. Overall, NPWT may enhance tissue vascularity around percutaneous devices, especially in patients with impaired wound healing. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2091-2101, 2019.

Peri-prosthetic tissue reaction to discontinuation of negative pressure wound therapy around porous titanium percutaneous devices.

Negative pressure wound therapy (NPWT) has been reported to limit epithelial downgrowth, one of the failure mechanisms of percutaneous devices. In a previous study, when NPWT was applied for 4 weeks (NPWT Group) to porous coated titanium percutaneous devices, downgrowth (5 ± 4%; mean ± one SD) was significantly reduced compared to untreated controls (Untreated Group) (16 ± 6%; p ≤ 0.01). However, it was unclear whether this beneficial effect was sustained when NPWT was discontinued. In order to test this, porous coated titanium percutaneous devices were implanted into 6 hairless guinea pigs. Post-surgery, animals received 4 weeks of NPWT treatment followed by 4 weeks of no treatment (Discontinued Group). At necropsy, the devices and surrounding tissues were harvested and processed. Quantitative downgrowth measurements and qualitative analyses of tissue characteristics were performed, and compared to historical controls (NPWT and Untreated Groups). The Discontinued Group, at 8 weeks, had significantly more downgrowth than the NPWT Group at 4 weeks (23 ± 3% vs. 5 ± 4%; p ≤ 0.01). At 8 weeks, the Discontinued Group qualitatively appeared to exhibit reduced numbers of blood vessels and increased degree of fibrosis compared to the NPWT Group at 4 weeks. This study suggests that NPWT will only be an effective treatment for limiting downgrowth if used continuously. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 564-572, 2019.