Microscopic characteristics of peri- and postmortem fracture surfaces.

This study investigated if microscopic surface features captured with a scanning electron microscope (SEM) effectively discriminate fracture timing. We hypothesized that microscopic fracture characteristics, including delamination, osteon pullout, and microcracks, may vary as bone elasticity decreases, elucidating perimortem and postmortem events more reliably than macroscopic analyses. Thirty-seven unembalmed, defleshed human femoral shafts from males (n=18) and females (n=2) aged 33-81 years were fractured at experimentally simulated postmortem intervals (PMIs) ranging from 1 to 60 warm weather days (250-40,600 ADH).

Do bone elasticity and postmortem interval affect forensic fractographic analyses?

Forensic fractographic features of bone reliably establish crack propagation in perimortem injuries. We investigated if similar fracture surface features characterize postmortem fractures. Experimentally induced peri- and postmortem fractures were used to assess if fractographic features vary as bone elasticity decreases during the postmortem interval (PMI).

Injectable catalyst-free "click" organic-inorganic nanohybrid (click-ON) cement for minimally invasive in vivo bone repair.

Injectable polymers have attracted intensive attention in tissue engineering and drug delivery applications. Current injectable polymer systems often require free-radical or heavy-metal initiators and catalysts for the crosslinking process, which may be extremely toxic to the human body. Here, we report a novel polyhedral oligomeric silsesquioxane (POSS) based strain-promoted alkyne-azide cycloaddition (SPAAC) "click" organic-inorganic nanohybrids (click-ON) system that can be click-crosslinked without any toxic initiators or catalysts.

Bifunctional hydrogel for potential vascularized bone tissue regeneration.

Most of the synthetic polymer-based hydrogels lack the intrinsic properties needed for tissue engineering applications. Here, we describe a biomimetic approach to induce the mineralization and vascularization of poly(ethylene glycol) (PEG)-based hydrogel to template the osteogenic activities. The strategy involves the covalent functionalization of oligo[poly(ethylene glycol) fumarate] (OPF) with phosphate groups and subsequent treatment of phosphorylated-OPF (Pi-OPF) hydrogels with alkaline phosphatase enzyme (ALP) and calcium.

Promoting Neuronal Outgrowth Using Ridged Scaffolds Coated with Extracellular Matrix Proteins.

Spinal cord injury (SCI) results in cell death, demyelination, and axonal loss. The spinal cord has a limited ability to regenerate, and current clinical therapies for SCI are not effective in helping promote neurologic recovery. We have developed a novel scaffold biomaterial that is fabricated from the biodegradable hydrogel oligo(poly(ethylene glycol)fumarate) (OPF).

Injectable Electrical Conductive and Phosphate Releasing Gel with Two-Dimensional Black Phosphorus and Carbon Nanotubes for Bone Tissue Engineering.

Injectable hydrogels have unique advantages for the repair of irregular tissue defects. In this study, we report a novel injectable carbon nanotube (CNT) and black phosphorus (BP) gel with enhanced mechanical strength, electrical conductivity, and continuous phosphate ion release for tissue engineering. The gel utilized biodegradable oligo(poly(ethylene glycol) fumarate) (OPF) polymer as the cross-linking matrix, with the addition of cross-linkable CNT-poly(ethylene glycol)-acrylate (CNTpega) to grant mechanical support and electric conductivity.

3D-printed scaffolds with carbon nanotubes for bone tissue engineering: Fast and homogeneous one-step functionalization.

Three-dimensional (3D) printing is a promising technology for tissue engineering. However, 3D-printing methods are limited in their ability to produce desired microscale features or electrochemical properties in support of robust cell adhesion, proliferation, and differentiation. This study addresses this deficiency by proposing an integrated, one-step, method to increase the cytocompatibility of 3D-printed scaffolds through functionalization leveraging conductive carbon nanotubes (CNTs).

3D bioprinting of oligo(poly[ethylene glycol] fumarate) for bone and nerve tissue engineering.

3D bioprinting is a promising new tissue restoration technique that enables the precise deposition of cells and growth factors in order to more closely mimic the structure and function of native organs. In this study, we report the development of a new bioink using oligo(poly[ethylene glycol] fumarate) (OPF), a photo-crosslinkable, and biodegradable polymer, for 3D bioprinting. In addition to OPF, a small portion of gelatin was also incorporated into the bioink to make it bio-printable.

Injectable Catalyst-Free Poly(Propylene Fumarate) System Cross-Linked by Strain Promoted Alkyne-Azide Cycloaddition Click Chemistry for Spine Defect Filling.

A new PPF-BCN/hyPCL32-N injectable system that can be cross-linked by catalyst-free, strain promoted alkyne-azide cycloaddition (SPAAC) click chemistry was developed for tissue engineering applications. The system consisted of two components: PPF-BCN, poly(propylene fumarate) (PPF) functionalized with (1,8,9s)-bicyclo[6.1.

Two-Dimensional Black Phosphorus and Graphene Oxide Nanosheets Synergistically Enhance Cell Proliferation and Osteogenesis on 3D Printed Scaffolds.

Two-dimensional (2D) materials have emerged as a new promising research topic for tissue engineering because of their ability to alter the surface properties of tissue scaffolds and thus improve their biocompatibility and cell affinity. Multiple 2D materials, such as graphene and graphene oxide (GO), have been widely reported to enhance cell adhesion and proliferation. Recently, a newly emerged black phosphorus (BP) 2D material has attracted attention in biomedical applications because of its unique mechanical and electrochemical characteristics.

Effect of Direct Electrical Current on Bones Infected with .

We are developing electrical approaches to treat biofilm-associated orthopedic foreign-body infection. Although we have previously shown that such approaches have antibiofilm activity, the effects on bone have not been assessed. Herein, low-amperage 200 μA fixed direct current (DC) was compared with no current, in a rat femoral foreign-body infection model.

Inhibition of STAT3 blocks protein synthesis and tumor metastasis in osteosarcoma cells.

Background: Osteosarcoma is the most common bone cancer. Despite advances, molecular mechanisms associated with osteosarcoma have not been fully understood. Hence, an effective treatment for osteosarcoma has yet to be developed.

Establishing a Current Good Manufacturing Practice Facility for Biomaterials and Biomolecules in an Academic Medical Center.

This article describes the feasibility and path to establishing a current good manufacturing practice biomaterial facility in an academic medical center. It presents a solution to overcome the "Valley of Death" in bench to bedside translation of biomaterials-based medical devices. It sets a good and feasible example to those who are interested in joining the path toward clinical practice/commercialization, and helps to spur other institutions and investigators to think about how they could incorporate in-house processes and facilities to help speed up the translation of their work into first-in-human trials.

Poly(Propylene Fumarate)-Hydroxyapatite Nanocomposite Can Be a Suitable Candidate for Cervical Cages.

A wide range of materials have been used for the development of intervertebral cages. Poly(propylene fumarate) (PPF) has been shown to be an excellent biomaterial with characteristics similar to trabecular bone. Hydroxyapatite (HA) has been shown to enhance biocompatibility and mechanical properties of PPF.

Cross-linkable graphene oxide embedded nanocomposite hydrogel with enhanced mechanics and cytocompatibility for tissue engineering.

Graphene oxide (GO) is an attractive material that can be utilized to enhance the modulus and conductivities of substrates and hydrogels. To covalently cross-link graphene oxide sheets into hydrogels, abundant cross-linkable double bonds were introduced to synthesize the graphene-oxide-tris-acrylate sheet (GO-TrisA). Polyacrylamide (PAM) nanocomposite hydrogels were then fabricated with inherent covalently and permanently cross-linked GO-TrisA sheets.

Functionalized Carbon Nanotube and Graphene Oxide Embedded Electrically Conductive Hydrogel Synergistically Stimulates Nerve Cell Differentiation.

Nerve regeneration after injury is a critical medical issue. In previous work, we have developed an oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel incorporated with positive charges as a promising nerve conduit. In this study, we introduced cross-linkable bonds to graphene oxide and carbon nanotube to obtain the functionalized graphene oxide acrylate (GOa) and carbon nanotube poly(ethylene glycol) acrylate (CNTpega).

Covalent crosslinking of graphene oxide and carbon nanotube into hydrogels enhances nerve cell responses.

Healing of nerve injuries is a critical medical issue. Biodegradable polymeric conduits are a promising therapeutic solution to provide guidance for axon growth in a given space, thus helping nerve heal. Extensive studies in the past decade reported that conductive materials could effectively increase neurite and axon extension in vitro and nerve regeneration in vivo.

Novel porous poly(propylene fumarate-co-caprolactone) scaffolds fabricated by thermally induced phase separation.

Scaffolds with porous structures are highly applicable for tissue engineering and regenerative medicine. In the present study, 3-dimensional poly(propylene fumarate-co-caprolactone) [P(PF-co-CL)] scaffolds were fabricated from a P(PF-co-CL)-dioxane-water ternary system through thermally induced phase separation (TIPS). Cloud points of P(PF-co-CL) in dioxane-water solutions increased with increased solute concentration, but increased dioxane composition decreased cloud point.

Hydrolysable core crosslinked particle for receptor-mediated pH-sensitive anticancer drug delivery.

Biodegradable micelle systems with both extracellular stabilities and specific targeting properties are highly desirable for anti-cancer drug delivery. Here, we report a biodegradable and crosslinkable poly(propylene fumarate)--poly(lactide--glycolide)--poly(ethylene glycol) (PPF-PLGA-PEG) copolymer conjugated with folate (FA) molecules for receptor-mediated delivery of doxorubicin. Micelles with folate ligands on surface and fumarate bonds within the core were self-assembled and crosslinked, which exhibited better stability against potential physiological conditions during and after drug administration.

Novel biodegradable poly(propylene fumarate)--poly(l-lactic acid) porous scaffolds fabricated by phase separation for tissue engineering applications.

Scaffolds with intrinsically interconnected porous structures are highly desirable in tissue engineering and regenerative medicine. In this study, three-dimensional polymer scaffolds with highly interconnected porous structures were fabricated by thermally induced phase separation of novel synthesized biodegradable poly(propylene fumarate)--poly(l-lactic acid) in a dioxane/water binary system. Defined porous scaffolds were achieved by optimizing conditions to attain interconnected porous structures.

Tunable tissue scaffolds fabricated by crosslink in phase separation system.

Three-dimensional (3-D) scaffolds with intrinsic porous structures are desirable in various tissue regeneration applications. In this study, a unique method that combines thermally induced phase separation with a photocrosslinking process was developed for the fabrication of 3-D crosslinked polymer scaffolds with densely interconnected porous structures. Biodegradable poly(propylene fumarate)--poly(L-lactic acid) with crosslinkable fumarate bonds were used as the structural polymer material and a dioxane/water binary system was applied for the phase separation.