Zucker Diabetic-Sprague Dawley Rats Have Impaired Peri-Implant Bone Formation, Matrix Composition, and Implant Fixation Strength.

An increasing number of patients with type 2 diabetes (T2DM) will require total joint replacement (TJR) in the next decade. T2DM patients are at increased risk for TJR failure, but the mechanisms are not well understood. The current study used the Zucker Diabetic-Sprague Dawley (ZDSD) rat model of T2DM with Sprague Dawley (SPD) controls to investigate the effects of intramedullary implant placement on osseointegration, peri-implant bone structure and matrix composition, and fixation strength at 2 and 10 weeks post-implant placement. Postoperative inflammation was assessed with circulating MCP-1 and IL-10 2 days post-implant placement. In addition to comparing the two groups, stepwise linear regression modeling was performed to determine the relative contribution of glucose, cytokines, bone formation, bone structure, and bone matrix composition on osseointegration and implant fixation strength. ZDSD rats had decreased peri-implant bone formation and reduced trabecular bone volume per total volume compared with SPD controls. The osseointegrated bone matrix of ZDSD rats had decreased mineral-to-matrix and increased crystallinity compared with SPD controls. Osseointegrated bone volume per total volume was not different between the groups, whereas implant fixation was significantly decreased in ZDSD at 2 weeks but not at 10 weeks. A combination of trabecular mineral apposition rate and postoperative MCP-1 levels explained 55.6% of the variance in osseointegration, whereas cortical thickness, osseointegration mineral apposition rate, and matrix compositional parameters explained 69.2% of the variance in implant fixation strength. The results support the growing recognition that both peri-implant structure and matrix composition affect implant fixation and suggest that postoperative inflammation may contribute to poor outcomes after TJR surgeries in T2DM patients. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The relative contribution of bone microarchitecture and matrix composition to implant fixation strength in rats.

Bone microarchitectural parameters significantly contribute to implant fixation strength but the role of bone matrix composition is not well understood. To determine the relative contribution of microarchitecture and bone matrix composition to implant fixation strength, we placed titanium implants in 12-week-old intact Sprague-Dawley rats, ovariectomized-Sprague-Dawley rats, and Zucker diabetic fatty rats. We assessed bone microarchitecture by microcomputed tomography, bone matrix composition by Raman spectroscopy, and implant fixation strength at 2, 6, and 10 weeks postimplantation. A stepwise linear regression model accounted for 83.3% of the variance in implant fixation strength with osteointegration volume/total volume (50.4%), peri-implant trabecular bone volume fraction (14.2%), cortical thickness (9.3%), peri-implant trabecular crystallinity (6.7%), and cortical area (2.8%) as the independent variables. Group comparisons indicated that osseointegration volume/total volume was significantly reduced in the ovariectomy group at Week 2 (~28%) and Week 10 (~21%) as well as in the diabetic group at Week 10 (~34%) as compared with the age matched Sprague-Dawley group. The crystallinity of the trabecular bone was significantly elevated in the ovariectomy group at Week 2 (~4%) but decreased in the diabetic group at Week 10 (~3%) with respect to the Sprague-Dawley group. Our study is the first to show that bone microarchitecture explains most of the variance in implant fixation strength, but that matrix composition is also a contributing factor. Therefore, treatment strategies aimed at improving bone-implant contact and peri-implant bone volume without compromising matrix quality should be prioritized.

Sclerostin antibody improves phosphate metabolism hormones, bone formation rates, and bone mass in adult Hyp mice.

X-linked hypophosphatemia (XLH) is caused by a loss-of-function mutation in the phosphate regulating gene with homology to endopeptidase located on the X chromosome (PHEX). Loss of functional PHEX results in elevated fibroblast growth factor 23 (FGF23), impaired phosphate reabsorption, and inhibited skeletal mineralization. Sclerostin, a protein produced primarily by osteocytes, suppresses bone formation by antagonizing canonical Wnt-signaling and is reported to be elevated in XLH patients. Our previous study reported that a monoclonal antibody to sclerostin (Scl-Ab) decreases FGF23 and increases phosphate and bone mass in growing Hyp mice (XLH murine model). In the current study, we investigated the efficacy of Scl-Ab in treating XLH pathophysiology in adult Hyp mice that are past the period of rapid skeletal growth (12 and 20-weeks old). We hypothesized that Scl-Ab would not only increase bone formation, bone strength and bone mass, but would also normalize phosphate regulating hormones, FGF23, parathyroid hormone (PTH), and vitamin 1,25(OH)2D. Scl-Ab treatment increased cortical area, trabecular bone volume fraction, trabecular bone formation rate, and the bending moment in both sexes of both age groups. Scl-Ab treatment suppressed circulating levels of intact FGF23 and c-term FGF23 in treated male and female wild-type and Hyp mice of both age groups and improved both vitamin 1,25(OH)2D and PTH. Scl-Ab treated Hyp mice also showed evidence of increased renal expression of the sodium-phosphate co-transporter, NPT2a, specifically in the female Hyp mice. Our study suggests that Scl-Ab treatment can improve several skeletal and metabolic pathologies associated with XLH, further establishes the role of sclerostin in the regulation of FGF23 and provides evidence that Scl-Ab can improve phosphate regulation by targeting the bone-renal axis.

Biomechanics of Implant Fixation in Osteoporotic Bone.

PURPOSE OF REVIEW: The purpose of this review is to critically evaluate the current literature regarding implant fixation in osteoporotic bone. RECENT FINDINGS: Clinical studies have not only demonstrated the growing prevalence of osteoporosis in patients undergoing total joint replacement (TJR) but may also indicate a significant gap in screening and treatment of this comorbidity. Osteoporosis negatively impacts bone in multiple ways beyond the mere loss of bone mass, including compromising skeletal regenerative capacity, architectural deterioration, and bone matrix quality, all of which could diminish implant fixation. Recent findings both in preclinical animal models and in clinical studies indicate encouraging results for the use of osteoporosis drugs to promote implant fixation. Implant fixation in osteoporotic bone presents an increasing clinical challenge that may be benefitted by increased screening and usage of osteoporosis drugs.

Exploration of plasma-enhanced chemical vapor deposition as a method for thin-film fabrication with biological applications.

Chemical vapor deposition (CVD) has been used historically for the fabrication of thin films composed of inorganic materials. But the advent of specialized techniques such as plasma-enhanced chemical vapor deposition (PECVD) has extended this deposition technique to various monomers. More specifically, the deposition of polymers of responsive materials, biocompatible polymers, and biomaterials has made PECVD attractive for the integration of biotic and abiotic systems. This review focuses on the mechanisms of thin-film growth using low-pressure PECVD and current applications of classic PECVD thin films of organic and inorganic materials in biological environments. The last part of the review explores the novel application of low-pressure PECVD in the deposition of biological materials.

Plasma-enhanced copolymerization of amino acid and synthetic monomers.

In this paper we report the use of plasma-enhanced chemical vapor deposition (PECVD) for the simultaneous deposition and copolymerization of an amino acid with other organic and inorganic monomers. We investigate the fundamental effects of plasma-enhanced copolymerization on different material chemistries in stable ultrathin coatings of mixed composition with an amino acid component. This study serves to determine the feasibility of a direct, facile method for integrating biocompatible/active materials into robust polymerized coatings with the ability to plasma copolymerize a biological molecule (L-tyrosine) with different synthetic materials in a dry, one-step process to form ultrathin coatings of mixed composition. This process may lead to a method of interfacing biologic systems with synthetic materials as a way to enhance the biomaterial-tissue interface and preserve biological activity within composite films.

SERS effects in silver-decorated cylindrical nanopores.

Optimization of pore diameter, the placement of nanoparticles, and the transmission of surface-enhanced Raman scattering (SERS) substrates are found to be very critical for achieving high SERS activity in porous alumina-membrane-based substrates. SERS substrates with a pore diameter of 355 nm incorporating silver nanoparticles show very high SERS activity with enhancement factors of 10(10) .

Direct probing of micromechanical properties of hydrogen-bonded layer-by-layer microcapsule shells with different chemical compositions.

The mechanical properties of hydrogen-bonded layer-by-layer (LbL) microcapsule shells constructed from tannic acid (TA) and poly(vinylpyrrolidone) (PVPON) components have been studied in both the dry and swollen states. In the dry state, the value of the elastic modulus was measured to be within 0.6-0.7 GPa, which is lower than the typical elastic modulus for electrostatically assembled LbL shells. Threefold swelling of the LbL shells in water results in a significant reduction of the elastic modulus to values well below 1 MPa, which is typical value seen for highly compliant gel materials. The increase of the molecular weight of the PVPON component from 55 to 1300 kDa promotes chain entanglements and causes a stiffening of the LbL shells with a more than 2-fold increase in elastic modulus value. Moreover, adding a polyethylenimine prime layer to the LbL shell affects the growth of hydrogen-bonded multilayers which consequently results in dramatically stiffer, thicker, and rougher LbL shells with the elastic modulus increasing by more than an order of magnitude, up to 4.3 MPa. An alternation of the elastic properties of very compliant hydrogen-bonded shells by variation of molecular weight is a characteristic feature of weakly bonded LbL shells. Such an ability to alter the elastic modulus in a wide range is critically important for the design of highly compliant microcapsules with tunable mechanical stability, loading ability, and permeability.

Label-free Raman mapping of surface distribution of protein a and IgG biomolecules.

We have demonstrated a nanoengineered substrate composed of micropatterned silver nanoparticles to be used for the label-free mapping of adsorbed biomolecules. We utilized surface-enhanced Raman scattering (SERS) phenomenon to monitor the known bioanalytes, protein A and human immunoglobulin G (IgG). The SERS substrate was composed of a poly(alylamine hydrochloride) (PAH)/poly(styrenesulfonate) (PSS) layer-by-layer (LbL) nanocoating micropatterned with silver nanoparticles confined to microscopic stripes. Selective adsorption of biomacromolecules is facilitated by the amine-terminated LbL nanocoating, which prevents the surface adsorption of positively charged protein A across the surface except on the patterned regions containing negatively charged silver nanoparticles. Furthermore, adsorption of IgG on predetermined regions is facilitated by the selective binding of the Fc region of IgG to protein A. This label-free SERS approach provides accurate, selective, and fast detection of protein A and IgG solutions with a nanomolar concentration, down to below 1 nM for IgG in solution. This method could also be utilized for the facile detection of proteins in field conditions as well as in clinical, forensic, industrial, and environmental laboratories.

Plasma amino acid coatings for a conformal growth of titania nanoparticles.

We report on the conformal synthesis of ultrathin films from the amino acid histidine on flat silicon substrates and 3D periodic polymer structures via plasma enhanced chemical vapor deposition. We demonstrate the efficient utilization of this functional amino acid nanocoating for the formation of individual titania nanoparticles with dimensions from 2 to 15 nm depending upon reduction conditions. The titania nanoparticles were grown directly on histidine-functionalized planar and 3D polymer substrates by a wet-chemistry method that showed uniform surface coverage that reached approximately 75%. This approach demonstrates the potential for modifying the optical properties of periodic porous polymeric structures via direct conformal growth of titania nanoparticles.

Facile plasma-enhanced deposition of ultrathin crosslinked amino acid films for conformal biometallization.

A novel method for the facile fabrication of conformal, ultrathin, and uniform synthetic amino acid coatings on a variety of practical surfaces by plasma-enhanced chemical vapor deposition is introduced. Tyrosine, which is utilized as an agent to reduce gold nanoparticles from solution, is sublimed into the plasma field and directly deposited on a variety of substrates to form a homogeneous, conformal, and robust polyamino acid coating in a one-step, solvent-free process. This approach is applicable to many practical surfaces and allows surface-induced biometallization while avoiding multiple wet-chemistry treatments that can damage many soft materials. Moreover, by placing a mask over the substrate during deposition, the tyrosine coating can be micropatterned. Upon its exposure to a solution of gold chloride, a network of gold nanoparticles forms on the surface, replicating the initial micropattern. This method of templated biometallization is adaptable to a variety of practical inorganic and organic substrates, such as silicon, glass, nitrocellulose, polystyrene, polydimethylsiloxane, polytetrafluoroethylene, polyethylene, and woven silk fibers. No special pretreatment is necessary, and the technique results in a rapid, conformal amino acid coating that can be utilized for further biometallization.

Thermoresponsive reversible behavior of multistimuli pluronic-based pentablock copolymer at the air-water interface.

Surface behavior of the pH- and thermoresponsive amphiphilic ABCBA pentablock copolymer has been studied with respect to the environmental conditions. We demonstrate that the pentablock copolymer poly((diethylaminoethyl methacrylate)-b-(ethylene oxide)-b-(propylene oxide)-b-(ethylene oxide)-b-(diethylaminoethyl methacrylate)) possesses reversible temperature changes at the air-water interface in a narrow pH range of the water subphase. Significant diversity in the surface morphology of pentablock copolymer monolayers at different pH and temperatures observed were related to the corresponding reorganization of central and terminal blocks. Remarkable reversible variations of the surface pressure observed for the Langmuir monolayers at pH 7.4 in the course of heating and cooling between 27 and 50 degrees C is associated with conformational transformations of terminal blocks crossing the phase line in the vicinity of the lower critical solution temperature point. The observed thermoresponsive surface behavior can be exploited for modeling of the corresponding behavior of pentablock copolymers adsorbed onto various biointerfaces for intracellular delivery for deeper understanding of stimuli-responsive transformations relevant to controlled drug and biomolecules release and retention.