Fourier-transform infrared spectroscopy imaging is a useful adjunct to routine histopathology to identify failure of polyethylene inlays in revision total hip arthroplasty.

The use of highly crosslinked ultra-high molecular weight polyethylene (XLPE) has significantly reduced the volumetric wear of acetabular liners, thereby reducing the incidence of osteolysis. However, contemporary components tend to generate smaller wear particles, which can no longer be identified using conventional histology. This technical limitation can result in imprecise diagnosis. Here, we report on two uncemented total hip arthroplasty cases (~7 years in situ) revised for periprosthetic fracture of the femur and femoral loosening, respectively. Both liners exhibited prominent wear. The retrieved pseudocapsular tissue exhibited a strong macrophage infiltration without microscopically identifiable polyethylene particles. Yet, using Fourier-transform infrared micro-spectroscopic imaging (FTIR-I), we demonstrated the prominent intracellular accumulation of polyethylene debris in both cases. This study shows that particle induced osteolysis can still occur with XLPE liners, even under 10 years in situ. Furthermore, we demonstrate the difficulty of determining the presence of polyethylene debris within periprosthetic tissue. Considering the potentially increased bioactivity of finer particles from XLPE compared to conventional liners, an accurate detection method is required, and new histopathological hallmarks of particle induced osteolysis are needed. FTIR-I is a great tool to that end and can help the accurate determination of foreign body tissue responses.

Methotrexate and sulforaphane loaded PBA-G5-PAMAM dendrimers as a combination therapy for anti-inflammatory response in an intra-articular joint arthritic animal model.

L-sulforaphane (LSF), a natural product developed from cruciferous vegetables, have shown potent anti-inflammatory effect in cancer as well as arthritis. However, the stable delivery of LSF remains a major challenge. Methotrexate (MTX) is currently the first line treatment for managing RA and is most effective in patients when used in combination with other anti-inflammatory or anti-rheumatic drugs. Here we developed phenylboronic acid-PAMAM dendrimer (PBA-G5D) nanoparticles conjugated MTX (MTX-PBA-G5D), and L-sulforaphane (LSF/PBA-G5D) loaded dendrimers. The MTX and LSF drug loading and release kinetics was analyzed using HPLC. The lipopolysaccharide (LPS) stimulated macrophages were treated with the formulations to study the inflammatory response in vitro. For in vivo studies, arthritis was induced in five-week-old female Wistar rats, and the MTX- and LSF/PBA-G5-D were injected via intra-articular injection for treatment and the arthritis reduction was scored by weight, knee diameter, and serum cytokine level measurement. The average size of the drug-nanoparticle conjugates ranged from 135 to 250 nm, with mostly cationic surface charges. The encapsulation efficiency of the drugs to the modified dendrimer was more than 60% with a slow release of drugs from the nanoparticles within 24 h at pH 7.4. Drugs in the nanoparticle formulation were biocompatible, with promising anti-inflammatory effects in vitro against LPS-activated murine macrophages. Further in vivo studies on arthritis induced female Wistar rats, revealed significant anti-arthritic effects based on the arthritic scoring from the knee diameter reading, and anti-inflammatory effects based on the serum cytokine levels. This study provides a promising strategy for utilizing PAMAM dendrimers as a nanocarrier for LSF delivery for RA therapy.

Is Heterotopic Ossification Removal From Alloplastic Temporomandibular Joint Prosthesis Using Er,Cr:YSGG Laser Superior to Conventional Methods?

PURPOSE: Heterotopic ossification (HO) formed over the major components and fixation screw heads of an alloplastic temporomandibular joint replacement (TMJR) prosthesis can result in decreased quality of life, limited function, prosthesis failure, and hinder prosthesis revision, replacement, or removal. This study simulated HO removal from the major components and fixation screw heads of alloplastic TMJR prostheses using an erbium, chromium-doped yttrium, scandium, gallium, and garnet (Er,Cr:YSGG) laser and compared the results to conventional methods of HO removal. The surface morphology and chemical structure of the exposed components were analyzed. The investigators hypothesize that HO removal with an Er,Cr:YSGG laser causes less damage to TMJR prosthesis components compared to conventional HO removal methods. METHODS: This multiple test descriptive analysis simulated HO removal from TMJR prostheses mounted to stereolithic models. Simulated HO removal was completed using a novel Er,Cr:YSGG laser method and conventional methods which utilized a fissure carbide bur in a high-speed rotary instrument, a standard osteotome, and an ultrasonic aspirator. Surfaces exposed on the TMJR prostheses were analyzed for morphological or chemical change using scanning electron microscopy, energy dispersive X-ray spectroscopy, and Raman spectroscopy. RESULTS: The Er,Cr:YSGG laser did not adversely affect the titanium screws or titanium components of the TMJR prostheses, while conventional methods of HO removal did. HO removal using the Er,Cr:YSGG laser and conventional methods both inflicted surface damage to the fossa ultrahigh molecular weight polyethylene component of the TMJR prostheses. CONCLUSION: Damage inflicted to titanium alloy or commercially pure titanium components of TMJR prostheses by conventional HO removal methods can be avoided by instead removing HO with an Er,Cr:YSGG laser. However, long exposure of the Er,Cr:YSGG laser to ultrahigh molecular weight polyethylene surfaces should be avoided. Additional research to expand on applications to other procedures and in other surgical fields is encouraged.

Non-ischaemic cardiomyopathy associated with elevated serum cobalt and accelerated wear of a metal-on-metal hip resurfacing.

A man in his late 30s developed non-ischaemic cardiomyopathy due to systemic cobalt toxicity associated with accelerated bearing surface wear from metal-on-metal hip resurfacing implanted in the previous 6 years. Following revision arthroplasty, the patient regained baseline cardiac function. Cobalt-induced cardiomyopathy is a grave condition that deserves early consideration due to potentially irreversible morbidity. We present this case to increase awareness, facilitate early detection and emphasise the need for research into the diagnosis and management of at-risk patients.

Amniotic growth factors enhanced human pre-adipocyte cell viability and differentiation under hypoxia.

One of the major drawbacks associated with autologous fat grafting is unpredictable graft retention. Various efforts to improve the survivability of these cells have been explored, but these methods are time-consuming, complex, and demand significant technical skill. In our study, we examine the use of cryopreserved amniotic membrane as a source of exogenous growth factors to improve adipocyte survivability under normal and hypoxic conditions. Human primary preadipocytes were cultured in a gelatin-ferulic acid (Gtn-FA) hydrogel with variable oxygen concentration and treated with amniotic membrane-derived condition medium (CM) for 7 days. This hydrogel provides a hypoxic environment and also creates a 3D cell culture to better mimic recipient site conditions. The O2 concentration in the hydrogel was measured by electron paramagnetic resonance oxygen imaging (EPROI). The conjugation of FA was confirmed by FTIR and NMR spectroscopy. The cell viability and adipocyte differentiation were analyzed by alamarBlue™ assay, Oil Red O staining, and RT-qPCR. The expression of genes: Pref-1, C/EBP ß, C/EBP α, PPAR-Æ´, SLC2A4, and VEGF-A were quantified. The cell viability results show that the 50% CM showed significantly higher cell pre-adipocyte cell viability. In addition, compared to normal conditions, hypoxia/CM provided higher PPAR-Æ´ (p < .05), SLC2A4, and VEGF-A (p < .05) (early and terminal differentiating markers) mRNA expression. This finding demonstrates the efficacy of amniotic CM supplementation as a novel way to promote adipocyte survival and retention via the expression of key gene markers for differentiation and angiogenesis.

Simultaneous Characterization of Implant Wear and Tribocorrosion Debris within Its Corresponding Tissue Response Using Infrared Chemical Imaging.

Biotribology is one of the key branches in the field of artificial joint development. Wear and corrosion are among fundamental processes which cause material loss in a joint biotribological system; the characteristics of wear and corrosion debris are central to determining the in vivo bioreactivity. Much effort has been made elucidating the debris-induced tissue responses. However, due to the complexity of the biological environment of the artificial joint, as well as a lack of effective imaging tools, there is still very little understanding of the size, composition, and concentration of the particles needed to trigger adverse local tissue reactions, including periprosthetic osteolysis. Fourier transform infrared spectroscopic imaging (FTIR-I) provides fast biochemical composition analysis in the direct context of underlying physiological conditions with micron-level spatial resolution, and minimal additional sample preparation in conjunction with the standard histopathological analysis workflow. In this study, we have demonstrated that FTIR-I can be utilized to accurately identify fine polyethylene debris accumulation in macrophages that is not achievable using conventional or polarized light microscope with histological staining. Further, a major tribocorrosion product, chromium phosphate, can be characterized within its histological milieu, while simultaneously identifying the involved immune cell such as macrophages and lymphocytes. In addition, we have shown the different spectral features of particle-laden macrophages through image clustering analysis. The presence of particle composition variance inside macrophages could shed light on debris evolution after detachment from the implant surface. The success of applying FTIR-I in the characterization of prosthetic debris within their biological context may very well open a new avenue of research in the orthopedics community.

Complex Rehabilitation for an Adolescent with Ectodermal Dysplasia-A 10-Year Follow-Up.

Maxillofacial rehabilitation of patients with ectodermal dysplasia (ED) often presents clinical challenges due to hypodontia and hypoplastic alveolar bone. This clinical report describes a 16-year-old patient suffering from ED who displayed severe hypodontia, maxillary retrusion and thin knife-edge alveolar crest. This patient was treated with distraction osteogenesis and a bone graft harvested from the iliac crest to correct maxillary retrusion and bone insufficiency. Six months later, implants were inserted. Then, implant-supported overdentures were completed. Although a new implant was reinserted during the 10-year follow-up, the results showed that combination surgical treatment achieved a predictable, functional and esthetic outcome in a patient suffering from ED.

Fourier transform infrared spectroscopic imaging of wear and corrosion products within joint capsule tissue from total hip replacements patients.

Implant debris generated by wear and corrosion is a prominent cause of joint replacement failure. This study utilized Fourier transform infrared spectroscopic imaging (FTIR-I) to gain a better understanding of the chemical structure of implant debris and its impact on the surrounding biological environment. Therefore, retrieved joint capsule tissue from five total hip replacement patients was analyzed. All five cases presented different implant designs and histopathological patterns. All tissue samples were formalin-fixed and paraffin-embedded. Unstained, 5 µm thick sections were prepared. The unstained sections were placed on BaF2 windows and deparaffinized with xylene prior to analysis. FTIR-I data were collected at a spectral resolution of 4 cm-1 using an Agilent Cary 670 spectrometer coupled with Cary 620 FTIR microscope. The results of study demonstrated that FTIR-I is a powerful tool that can be used complimentary to the existing histopathological evaluation of tissue. FTIR-I was able to distinguish areas with different cell types (macrophages, lymphocytes). Small, but distinct differences could be detected depending on the state of cells (viable, necrotic) and depending on what type of debris was present (polyethylene [PE], suture material, and metal oxides). Although, metal oxides were mainly below the measurable range of FTIR-I, the infrared spectra of tissues exhibited noticeable difference in their presence. Tens of micrometer sized polyethylene particles could be easily imaged, but also accumulations of submicron particles could be detected within macrophages. FTIR-I was also able to distinguish between PE debris, and other birefringent materials such as suture. Chromium-phosphate particles originating from corrosion processes within modular taper junctions of hip implants could be identified and easily distinguished from other phosphorous materials such as bone. In conclusion, this study successfully demonstrated that FTIR-I is a useful tool that can image and determine the biochemical information of retrieved tissue samples over tens of square millimeters in a completely label free, nondestructive, and objective manner. The resulting chemical images provide a deeper understanding of the chemical nature of implant debris and their impact on chemical changes of the tissue within which they are embedded.