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1.
Animal Model Exp Med ; 7(2): 145-155, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38525803

RESUMO

BACKGROUND: Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues. Vitamin E is an antioxidant with potential anti-fibroblastic effect. The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis. METHODS: We simulated knee replacement in 16 male Sprague-Dawley rats. We immobilized the surgical leg with a suture in full flexion. The control groups were killed at 2 and 12 weeks (n = 5 per group), and the test group was supplemented daily with vitamin E (0.2 mg/mL) in their drinking water for 12 weeks (n = 6). We performed histological staining to investigate the presence and severity of arthrofibrosis. Immunofluorescent staining and α2-macroglobulin (α2M) enzyme-linked immunosorbent assay (ELISA) were used to assess local and systemic inflammation. Static weight bearing (total internal reflection) and range of motion (ROM) were collected for functional assessment. RESULTS: The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups. Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue. Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels. The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group. CONCLUSIONS: This model is viable for simulating arthrofibrosis after joint replacement. Vitamin E may benefit postsurgical arthrofibrosis, and further studies are needed for dosing requirements.


Assuntos
Fibrose , Amplitude de Movimento Articular , Ratos Sprague-Dawley , Vitamina E , Animais , Vitamina E/farmacologia , Vitamina E/administração & dosagem , Vitamina E/uso terapêutico , Masculino , Ratos , Amplitude de Movimento Articular/efeitos dos fármacos , Artroplastia do Joelho , Artropatias/prevenção & controle , Artropatias/etiologia , Modelos Animais de Doenças
2.
J Orthop Res ; 42(2): 306-316, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37593816

RESUMO

Majority of ultrahigh molecular weight polyethylene (UHMWPE) medical devices used in total joint arthroplasty are cross-linked using gamma radiation to improve wear resistance. Alternative methods of cross-linking are urgently needed to replace gamma radiation due to rapid decline in its supply. Peroxide cross-linking is a candidate method with widespread industrial applications. Oxidative stability and biocompatibility, which are critical requirements for medical device applications, can be achieved using vitamin-E as an additive and by removing peroxide by-products through high-temperature melting, respectively. We investigated compression molded UHMWPE/vitamin-E/di-cumyl peroxide blends followed by high-temperature melting in inert gas as a material candidate for tibial knee inserts. Wear resistance increased and mechanical properties remained largely unchanged. Oxidation induction time was higher than most of the other clinically available formulations. The material passed the local-end point biocompatibility tests per ISO 10993. Compounds found in exhaustive extraction were of no concern with margin-of-safety values well above the accepted level, indicating a desirable toxicological risk profile. Statement of Clinical Significance: Peroxide cross-linked, vitamin-E stabilized, and high-temperature melted UHMWPE has recently been cleared for clinical use in tibial knee inserts. With all the salient characteristics needed in a material that can provide superior long-term performance in total joint patients, peroxide cross-linking can replace the gamma radiation cross-linking of UHMWPE.


Assuntos
Peróxidos , Vitamina E , Humanos , Polietilenos , Artroplastia , Vitaminas , Teste de Materiais
3.
J Control Release ; 361: 20-28, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37451545

RESUMO

The high prevalence of opioid addiction and the shortcomings of systemic opioids has increased the pace of the search for alternative methods of pain management. The local delivery of pain medications has started to be used as a tool for pain management and to decrease the use of systemic opioids for these patients. Here, we explored an in-situ polymerizable hydrogel system for the local delivery of analgesics and nonsteroid anti-inflammatory drugs (NSAID) for orthopaedic applications. We synthesized a series of methacrylated oligomeric polyethylene glycol-co-lactic acid polymer using microwave radiation for the delivery of bupivacaine hydrochloride as an analgesic and ketorolac tromethamine as an NSAID. We determined drug elution and gel degradation profiles in vitro. Biocompatibility was assessed against osteoblasts in vitro and by histological analysis after subcutaneous implantation for 4 weeks in vivo. Intra-articular and systemic concentrations and pharmacokinetic parameters were estimated using a two-compartment pharmacodynamic model based on in-vitro elution profiles. This type of in-situ applicable hydrogels is promising for extending the local efficacy of pain medication and further reducing the need for opioids.


Assuntos
Analgésicos Opioides , Hidrogéis , Humanos , Hidrogéis/uso terapêutico , Polimerização , Anti-Inflamatórios não Esteroides , Analgésicos , Dor/tratamento farmacológico
4.
Nature ; 537(7618): 84-88, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27409814

RESUMO

The use of femtosecond laser pulses allows precise and thermal-damage-free removal of material (ablation) with wide-ranging scientific, medical and industrial applications. However, its potential is limited by the low speeds at which material can be removed and the complexity of the associated laser technology. The complexity of the laser design arises from the need to overcome the high pulse energy threshold for efficient ablation. However, the use of more powerful lasers to increase the ablation rate results in unwanted effects such as shielding, saturation and collateral damage from heat accumulation at higher laser powers. Here we circumvent this limitation by exploiting ablation cooling, in analogy to a technique routinely used in aerospace engineering. We apply ultrafast successions (bursts) of laser pulses to ablate the target material before the residual heat deposited by previous pulses diffuses away from the processing region. Proof-of-principle experiments on various substrates demonstrate that extremely high repetition rates, which make ablation cooling possible, reduce the laser pulse energies needed for ablation and increase the efficiency of the removal process by an order of magnitude over previously used laser parameters. We also demonstrate the removal of brain tissue at two cubic millimetres per minute and dentine at three cubic millimetres per minute without any thermal damage to the bulk.


Assuntos
Temperatura Baixa , Temperatura Alta , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Lasers/efeitos adversos , Animais , Encéfalo/cirurgia , Bovinos , Córnea/cirurgia , Dentina/cirurgia , Humanos , Terapia a Laser/instrumentação , Ratos , Fatores de Tempo
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