5 research outputs found
3-vinyl-1,2,4-triazine as platform for conjugate addition/hetero-Diels-Alder/retro-Diels-Alder cascade reaction
National audienc
Designer Dual Therapy Nanolayered Implant Coatings Eradicate Biofilms and Accelerate Bone Tissue Repair
Infections
associated with orthopedic implants cause increased
morbidity and significant healthcare cost. A prolonged and expensive
two-stage procedure requiring two surgical steps and a 6–8
week period of joint immobilization exists as today’s gold
standard for the revision arthroplasty of an infected prosthesis.
Because infection is much more common in implant replacement surgeries,
these issues greatly impact long-term patient care for a continually
growing part of the population. Here, we demonstrate that a single-stage
revision using prostheses coated with self-assembled, hydrolytically
degradable multilayers that sequentially deliver the antibiotic (gentamicin)
and the osteoinductive growth factor (BMP-2) in a time-staggered manner
enables both eradication of established biofilms and complete and
rapid bone tissue repair around the implant in rats with induced osteomyelitis.
The nanolayered construct allows precise independent control of release
kinetics and loading for each therapeutic agent in an infected implant
environment. Antibiotics contained in top layers can be tuned to provide
a rapid release at early times sufficient to eliminate infection,
followed by sustained release for several weeks, and the underlying
BMP-2 component enables a long-term sustained release of BMP-2, which
induced more significant and mechanically competent bone formation
than a short-term burst release. The successful growth factor-mediated
osteointegration of the multilayered implants with the host tissue
improved bone-implant interfacial strength 15-fold when compared with
the uncoated one. These findings demonstrate the potential of this
layered release strategy to introduce a durable next-generation implant
solution, ultimately an important step forward to future large animal
models toward the clinic
Integrated Biosensor for Rapid and Point-of-Care Sepsis Diagnosis
Sepsis
is an often fatal condition that arises when the immune
response to an infection causes widespread systemic organ injury.
A critical unmet need in combating sepsis is the lack of accurate
early biomarkers that produce actionable results in busy clinical
settings. Here, we report the development of a point-of-care platform
for rapid sepsis detection. Termed IBS (integrated biosensor for sepsis),
our approach leverages (i) the pathophysiological role of cytokine
interleukin-3 (IL-3) in early sepsis and (ii) a hybrid magneto-electrochemical
sensor for IL-3 detection. The developed platform produces test results
within 1 h from native blood samples and detects IL-3 at a sensitivity
of <10 pg/mL; this performance is >5-times faster and >10-times
more sensitive than conventional enzyme-linked immunoadsorbent assays,
the current gold standard. Using clinical samples, we show that elevated
plasma IL-3 levels are associated with high organ failure rate and
thus greater risk of mortality, confirming the potential of IL-3 as
a sepsis diagnostic biomarker. With further system development (<i>e</i>.<i>g</i>., full automation, data security measures)
and rigorous validation studies, the compact and fast IBS could be
a practical clinical tool for timely diagnosis and proactive treatment
of sepsis
Integrated Biosensor for Rapid and Point-of-Care Sepsis Diagnosis
Sepsis
is an often fatal condition that arises when the immune
response to an infection causes widespread systemic organ injury.
A critical unmet need in combating sepsis is the lack of accurate
early biomarkers that produce actionable results in busy clinical
settings. Here, we report the development of a point-of-care platform
for rapid sepsis detection. Termed IBS (integrated biosensor for sepsis),
our approach leverages (i) the pathophysiological role of cytokine
interleukin-3 (IL-3) in early sepsis and (ii) a hybrid magneto-electrochemical
sensor for IL-3 detection. The developed platform produces test results
within 1 h from native blood samples and detects IL-3 at a sensitivity
of <10 pg/mL; this performance is >5-times faster and >10-times
more sensitive than conventional enzyme-linked immunoadsorbent assays,
the current gold standard. Using clinical samples, we show that elevated
plasma IL-3 levels are associated with high organ failure rate and
thus greater risk of mortality, confirming the potential of IL-3 as
a sepsis diagnostic biomarker. With further system development (<i>e</i>.<i>g</i>., full automation, data security measures)
and rigorous validation studies, the compact and fast IBS could be
a practical clinical tool for timely diagnosis and proactive treatment
of sepsis