Osteomimetic Polyphosphate Modified Graphite as a Degradable, Cell Instructive Scaffold for Bone Regeneration (Anne, Brian)
Severe bone injury can occur due to traumatic events such as
automobile accidents or battlefield injuries, and every year millions of
patients in the United States undergo procedures, often invasive and painful,
every year to correct these deformities. Currently, autologous tissue
transplantation or implantation of prosthetic devices is used as a therapeutic
treatment for large defect areas: both therapies suffer limitations. To
encourage healing beyond this critical juncture, we have designed a biomaterial
that innately encourages regeneration by sustaining osteogenic stem cell
differentiation and muting fibrotic differentiation.
In
this way, tissue engineering has emerged as a potential treatment alternative
for individuals plagued with debilitating bone injuries or diseases, as
synthetic materials have potential to direct the healing response. In the
Sydlik Group, we have developed a chemical procedure that lets us transform
graphite into a degradable, cell-instructive scaffold that recapitulates the
properties of native bone to induce bone healing. Starting from graphite, we
oxidize to graphene oxide (GO) and perform further chemistry to give
phosphate-modified graphene (PG) materials. PG can be hot pressed into
bone-shaped constructs that offer excellent and tunable mechanical properties,
degradability, controllable surface chemistry, and biocompatibility.
Next-generation
medical adhesives have the potential to replace sutures as the gold standard of
care for wound closure. However, current adhesives like VetbondTM
and Histoacryl® face challenges to widespread implementation,
including brittleness and an aqueous degradation pathway that releases
formaldehyde. To address these limitations, we designed novel therapeutic
methacrylate (TMA) monomers on the molecular level to impart tunable mechanical
properties, increased water stability, and programmable
bioactivity to cyanoacrylate adhesives. Uniquely, TMAs take advantage of covalent controlled release as a tool to
control the delivery of therapeutic small molecules from different covalent
bonds (anhydride, ester, or amide) directly to injured tissue. Covalent controlled
release from composite TMA adhesives, prepared as 10% TMA by weight in VetbondTM,
was shown to follow the order predicted by hydrolysis chemistry, with the
anhydride-tether TMA adhesive delivering therapeutics on the same order of
magnitude and time scale as topical
medications (8.8 ± 1.5 mg per gram of adhesive after 3.4 h). Compared to
VetbondTM, composite TMA adhesives have shown up to a 71% reduction
in formaldehyde release, improved cytocompatibility in cells present in healing
wounds, and up to a 319% increase in toughness (including both greater lap
shear strength and ductility). Further, all TMA adhesives are effective at
adhering to porcine skin. These transformative materials bring sophisticated
controlled release technology to the field of medical adhesives, combining
effective, convenient tissue fixation with programmable bioactivity.
Studying the thermomechanical properties of copolymers to develop laboratory, theoretical, and communication skills essential to a successful research career (Will)
Graduate and undergraduate education is the key to success in all branches of science: in industry and academia alike. In particular, Carnegie Mellon University is widely recognized as a leader in polymer chemistry, and many classes are offered, as well as research experiences, to prepare students for graduate studies and careers in the field. Despite this breadth, a comprehensive class that provides the hands on laboratory, writing, and presentation skills, as well as theory in the field does not exist. Even after many classes and years of research experience, students enter graduate school or the work force still uncertain about the demands and expectations of how to learn new laboratory techniques, what is required in the writing of a paper or a grant, and what constitutes a good scientific presentation. Further, students many rely on instrumentation to produce results, without a deeper understanding of the principles applied by that instrument.
This
project overcomes these deficits and equips students with the analytical and
practical skills necessary to be successful in a prestigious research
environment. We have designed a course centered around a laboratory experiment.
Specifically, students use advanced Schlenk technique to synthesize a series of
acrylate copolymers. These copolymers are designed to demonstrate the effect of
copolymerization on the thermomechanical properties of the polymers, teaching
the students, in effect, material design. Students analyze these polymers using
techniques essential to the field, including H-NMR (including end group
analysis), gel permeation chromatography (GPC), thermogravimentric analysis
(TGA), dynamic scanning calorimetry (DSC), and dynamic mechanical analysis
(DMA). The laboratory techniques are accompanied by in class lectures
describing the theory and mathematics behind the measurements. Further, the
course is augmented with opportunities to teach technical communication skills,
including creative grant writing, technical presentations, writing a compelling
journal article, and making effective images and figures.
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