The two leading causes of failure for joint arthroplasty prostheses are aseptic loosening and periprosthetic joint infection. With the number of primary and revision joint replacement surgeries on the rise, strategies to mitigate these failure modes have become increasingly important. Much of the recent work in this field has focused on the design of coatings either to prevent infection while ignoring bone mineralization or vice versa, to promote osseointegration while ignoring microbial susceptibility. However, both coating functions are required to achieve long-term success of the implant; therefore, these two modalities must be evaluated in parallel during the development of new orthopaedic coating strategies. In this review, we discuss recent progress and future directions for the design of multifunctional orthopaedic coatings that can inhibit microbial cells while still promoting osseointegration.
Here we present the design of an engineered, elastin-like protein (ELP) that is chemically modified to enable stable coatings on the surfaces of titanium-based dental and orthopaedic implants by novel photocrosslinking and solution processing steps. The ELP includes an extended RGD sequence to confer bio-signaling and an elastin-like sequence for mechanical stability. ELP thin films were fabricated on cp-Ti and Ti6Al4V surfaces using scalable spin and dip coating processes with photoactive covalent crosslinking through a carbene insertion mechanism. The coatings withstood procedures mimicking dental screw and hip replacement stem implantations, a key metric for clinical translation. They promoted rapid adhesion of MG63 osteoblast-like cells, with over 80% adhesion after 24 hours, compared to 38% adhesion on uncoated Ti6Al4V. MG63 cells produced significantly more mineralization on ELP coatings compared to uncoated Ti6Al4V. Human bone marrow mesenchymal stem cells (hMSCs) had an earlier increase in alkaline phosphatase activity, indicating more rapid osteogenic differentiation and mineral deposition on adhesive ELP coatings. Rat tibia and femur in vivo studies demonstrated that cell-adhesive ELP-coated implants increased bone-implant contact area and interfacial strength after one week. These results suggest that ELP coatings withstand surgical implantation and promote rapid osseointegration, enabling earlier implant loading and potentially preventing micromotion that leads to aseptic loosening and premature implant failure.
Photocrosslinkable, protein-engineered biomaterials combine a rapid, controllable, cytocompatible crosslinking method with a modular design strategy to create a new family of bioactive materials. These materials have a wide range of biomedical applications, including the development of bioactive implant coatings, drug delivery vehicles, and tissue engineering scaffolds. We present the successful functionalization of a bioactive elastin-like protein with photoreactive diazirine moieties. Scalable synthesis is achieved using a standard recombinant protein expression host followed by site-specific modification of lysine residues with a heterobifunctional N-hydroxysuccinimide ester-diazirine crosslinker. The resulting biomaterial is demonstrated to be processable by spin coating, drop casting, soft lithographic patterning, and mold casting to fabricate a variety of two- and three-dimensional photocrosslinked biomaterials with length scales spanning the nanometer to millimeter range. Protein thin films proved to be highly stable over a three-week period. Cell-adhesive functional domains incorporated into the engineered protein materials were shown to remain active post-photo-processing. Human adipose-derived stem cells achieved faster rates of cell adhesion and larger spread areas on thin films of the engineered protein compared to control substrates. The ease and scalability of material production, processing versatility, and modular bioactive functionality make this recombinantly engineered protein an ideal candidate for the development of novel biomaterial coatings, films, and scaffolds.
Background While fat grafting can address many soft tissue deficits, results remain inconsistent. In this study, we compared physical properties of fat following injection using an automated, low shear device or the modified Coleman technique. Methods Lipoaspirate was obtained from nine patients and processed for injection using either a modified Coleman technique or with an automated, low shear device. Fat was passed through a 2 mm cannula and compared to minimally processed fat. A rheometer was used to measure the storage modulus and shear rate at which tissues began to lose their solid-like properties. Viscosity was also measured and gross properties of treatment groups were qualitatively evaluated with a glass slide test. Results Fat injected through an automated, low shear device closely matched physical properties of minimally processed fat. The storage modulus (G′) of fat for the device group was greater than the modified Coleman group and the onset of breakdown was delayed. Similarly, viscosity measurement of fat from the automated device closely matched minimally processed fat and was greater than the modified Coleman group. Conclusions The physical properties of lipoaspirate processed using an automated, low shear device with a 2 mm cannula preserved the intactness of fat more than the modified Coleman technique. Our rheological data demonstrate less damage using an automated device compared to modified Coleman technique and potentially support its use for improved fat graft integrity.
Selective laser sintering (SLS) is a prominent 3D printing modality that typically uses a polyamide (PA) powder as the substrate. One commercially available SLS material is known as PA2200, which is comprised of nylon 12 and titanium dioxide (TiO2) and is widely used to generate 3D-printed parts. Here, we report a unique optical photoluminescence (PL) characteristic of native, white PA2200, in which it yields a persistent, phosphorescence-type emission. An analysis of luminescence imaging data with emission measurements demonstrated that the anatase phase of the titanium dioxide additive is the source of the persistent PL properties. This characteristic of PA2200 enables advanced optical imaging applications, as demonstrated by luminescence imaging of an anatomical rat skeleton and a novel Derenzo-type phantom on a commercial image station. In summary, the light emission properties of PA2200 induced by the presence of anatase titanium dioxide open the door to a vast new array of complex optical applications, including the generation of imaging phantoms for training, calibration, and quality control.
Depilation (that is, hair removal) is a necessary prerequisite for many small animal surgeries and optical imaging experiments. Over-the-counter depilatory creams are widely used, owing to their efficacy, safety, and low rates of skin irritation and infection. However, the use of these creams is generally messy and time-consuming and generates considerable waste. Furthermore, the process itself varies markedly among laboratories. Here we present a 3D-printed device that simplifies the depilation procedure by integrating 3 key elements: 1) a multiple-port, self-scavenging anesthesia manifold, 2) curved animal holders with flow-through slats, and 3) a removable waste collection tray. Reflecting insights gained from an international survey about depilatory lab procedures that highlighted the lack of standardized protocols, this apparatus is designed to improve the neatness, throughput, and safety of mouse depilation, resulting in efficient and repeatable processes that bolster the welfare of both researchers and subjects.
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