Sustained zinc release in cooperation with CaP scaffold promoted bone regeneration via directing stem cell fate and triggering a pro-healing immune stimuli.

Metal ions have been identified as important bone metabolism regulators and widely used in the field of bone tissue engineering, however their exact role during bone regeneration remains unclear. Herein, the aim of study was to comprehensively explore the interactions between osteoinductive and osteo-immunomodulatory properties of these metal ions. In particular, the osteoinductive role of zinc ions (Zn2+), as well as its interactions with local immune microenvironment during bone healing process, was investigated in this study using a sustained Zn2+ delivery system incorporating Zn2+ into ß-tricalcium phosphate/poly(L-lactic acid) (TCP/PLLA) scaffolds. The presence of Zn2+ largely enhanced osteogenic differentiation of periosteum-derived progenitor cells (PDPCs), which was coincident with increased transition from M1 to M2 macrophages (M[Formula: see text]s). We further confirmed that induction of M2 polarization by Zn2+ was realized via PI3K/Akt/mTOR pathway, whereas marker molecules on this pathway were strictly regulated by the addition of Zn2+. Synergically, this favorable immunomodulatory effect of Zn2+ further improved the osteogenic differentiation of PDPCs induced by Zn2+ in vitro. Consistently, the spontaneous osteogenesis and pro-healing osteoimmunomodulation of the scaffolds were thoroughly identified in vivo using a rat air pouch model and a calvarial critical-size defect model. Taken together, Zn2+-releasing bioactive ceramics could be ideal scaffolds in bone tissue engineering due to their reciprocal interactions between osteoinductive and immunomodulatory characteristics. Clarification of this synergic role of Zn2+ during osteogenesis could pave the way to develop more sophisticated metal-ion based orthopedic therapeutic strategies.

Bone combined cement grafting in giant cell tumor around the knee reduces mechanical failure.

OBJECTIVES: The aims of our study are (1) to explore the risk factors of mechanical failure (MF), (2) to figure out an index to evaluate this risk, and (3) to select an optimal reconstruction strategy to reduce this risk. METHODS: We retrospectively reviewed 104 patients from Dec. 2008 to Mar. 2016, undergone extensive knee curettages in our institution. Radiographs and post-operative interviews were used to classified cases of MF. Relative factors (age, tumor location, the invaded area, etc.) were also collected and analyzed by SPSS software. RESULTS: Thick subchondral bony layer (p = 0.006) and combined grafting of the cement and bone (p = 0.006) had lower risk of mechanical failure. Mechanical failure appeared to happen in the femur (p = 0.012) more easily. The ROC curve (AUC = 0.722) reveals that less post-operative bony layer (≤ 3.3 mm) is more likely to cause mechanical failure. The Kaplan-Meier survival curve showing increased survival in those patients after a combination grafting surgery (HR, 3.799; p = 0.006). CONCLUSION: Based on our study results, combined grafting of the cement and bone reduced the risk of mechanical failure in the knee due to the thin subchondral bone layer (SCB), especially in the femur.

Antibacterial and hydroxyapatite-forming coating for biomedical implants based on polypeptide-functionalized titania nanospikes.

Titanium (Ti)-based implants often suffer from detrimental bacterial adhesion and inefficient healing, so it is crucial to design a dual-functional coating that prevents bacterial infection and enhances bioactivity for a successful implant. Herein, we successfully devised a cationic polypeptide (Pep)-functionalized biomimetic nanostructure coating with superior activity, which could not only kill pathogenic bacteria rapidly and inhibit biofilm formation for up to two weeks, but also promote in situ hydroxyapatite (HAp) formation. Specifically, a titania (TiO2) nanospike coating (TNC) was fabricated by alkaline hydrothermal treatment firstly, followed by immobilization of rationally synthesized Pep via robust coordinative interactions, named TNPC. This coating was able to effectively kill (>99.9%) both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria, while being non-toxic to murine MC3T3-E1 osteoblastic cells. Furthermore, the in vivo infection studies denoted that the adherent bacteria numbers on the TNPC implants were significantly reduced by 6 orders of magnitude than those on the pure Ti implants (p < 0.001). Importantly, in the presence of cationic amino groups and residual Ti-OH groups, substantial HAp deposition on the TNPC surface in Kokubo's simulated body fluid (SBF) occurred after 14 days. Altogether, our results support the clinical potential of this biomimetic dual-functional coating as a new approach with desirable antibacterial properties and HAp-forming ability in orthopedic and dental applications.

[Mucoadhesive buccal films of tramadol for effective pain management]. / Filmes bucais mucoadesivos de tramadol para o controle eficaz da dor.

BACKGROUND AND OBJECTIVES: Tramadol hydrochloride is a centrally-acting synthetic opioid analgesic binding to specific opioid receptors. It is used in the management of chronic pain and is recommended as first line drug in the treatment of postoperative or orthopedic injury induced acute pain. The present work is designed to prepare and evaluate mucoadhesive buccal film of tramadol hydrochloride as a novel form of prolonged analgesia for patients with orthopedic injuries. METHODS: Buccal films of tramadol hydrochloride were prepared by solvent casting method. The prepared films were evaluated for the various evaluation parameters like thickness, surface pH, weight uniformity, content uniformity, folding endurance, swelling index, in vitro drug release study, in vitro test for mucoadhesion and in vivo studies (primary mucosal irritancy test and analgesic activity). RESULTS: All the formulations exhibited good results for physicochemical characterizations. In in vitro drug release study the films exhibited controlled release more than 12hours. The formulation BFT2 (containing chitosan and PVP K-90) showed no irritant effect on buccal mucosa and elicit the significant in vivo analgesic activity with 57.14% analgesia against that of standard (61.04%). It was concluded that the mucoadhesive films of tramadol hydrochloride can be effectively used to alleviate the severe pain of orthopedic injuries with prompt onset and prolonged action.

[Clinical studies on effect of bone cement filling on articular cartilage of the knee after curettage of giant cell tumor].

OBJECTIVE: To evaluate the effect of bone cement filling on articular cartilage injury after curettage of giant cell tumor around the knee. METHODS: Fifty-three patients with giant cell tumor who accorded with the inclusion criteria were treated between January 2000 and December 2011, and the clinical data were retrospectively analyzed. There were 30 males and 23 females, aged 16-69 years (mean, 34.2 years). The lesion located at the distal femur in 28 cases and at the proximal tibia in 25 cases. According to Campanacci grade, there were 6 patients at grade I, 38 at grade II, and 9 at grade III. Of 53 patients, 42 underwent curettage followed by bone cement filling, and 11 received curettage followed by bone grafts in the subchondral bony area and bone cement filling. Two groups were divided according to whether secondary osteoarthritis occurred or not during postoperative follow-up. The gender, age, lesion site, the subchondral residual bone thickness, tumor cross section, preoperative Campanacci grade, subchondral bone graft, and Enneking function score were compared between 2 groups, and multivariate logistic regression analysis was done. RESULTS: All incisions healed by first intention. The average follow-up time was 65 months (range, 23-158 months). Of 53 cases, 37 (69.8%) had no osteoarthritis, and 16 (30.2%) had secondary osteoarthritis. Three cases (5.7%) recurred during the follow-up period. Univariate logistic regression analysis showed no significant difference in gender, age, lesion site, and Campanacci grade between 2 groups (P > 0.1); difference was significant in the subchondral residual bone thickness, tumor cross section, Enneking function score, and subchondral bone graft (P < 0.1). The multivariate logistic regression analysis showed that the decreased subchondral residual bone thickness, the increased tumor cross section, and no subchondral bone graft are the risk factors of postoperative secondary osteoarthritis (P < 0.05). CONCLUSION: Curettage of giant cell tumor around the knee followed by bone cement filling can increase the damage of cartilage, and subchondral bone graft can delay or reduce cartilage injury.

Mucoadhesive buccal films of tramadol for effective pain management / Filmes bucais mucoadesivos de tramadol para o controle eficaz da dor

Abstract Background and objectives: Tramadol hydrochloride is a centrally-acting synthetic opioid analgesic binding to specific opioid receptors. It is used in the management of chronic pain and is recommended as first line drug in the treatment of postoperative or orthopedic injury induced acute pain. The present work is designed to prepare and evaluate mucoadhesive buccal film of tramadol hydrochloride as a novel form of prolonged analgesia for patients with orthopedic injuries. Methods: Buccal films of tramadol hydrochloride were prepared by solvent casting method. The prepared films were evaluated for the various evaluation parameters like thickness, surface pH, weight uniformity, content uniformity, folding endurance, swelling index, in vitro drug release study, in vitro test for mucoadhesion and in vivo studies (primary mucosal irritancy test and analgesic activity). Results: All the formulations exhibited good results for physicochemical characterizations. In in vitro drug release study the films exhibited controlled release more than 12 hours. The formulation BFT2 (containing chitosan and PVP K-90) showed no irritant effect on buccal mucosa and elicit the significant in vivo analgesic activity with 57.14% analgesia against that of standard (61.04%). It was concluded that the mucoadhesive films of tramadol hydrochloride can be effectively used to alleviate the severe pain of orthopedic injuries with prompt onset and prolonged action.

Resumo Justificativa e objetivos: O cloridrato de tramadol é um analgésico opioide de ação central que se liga a receptores opioides específicos. É usado no tratamento de dor crônica e recomendado como fármaco de primeira linha para o tratamento no pós-operatório ou em dor aguda induzida por lesão ortopédica. O presente estudo visa a preparar e avaliar o filme bucal mucoadesivo de cloridrato de tramadol como uma nova forma de analgesia prolongada para pacientes com lesões ortopédicas. Método: Filmes bucais de cloridrato de tramadol foram preparados pelo método de evaporação de solvente. Os filmes preparados foram avaliados para os vários parâmetros de avaliação, como espessura, pH da superfície, uniformidade do peso, uniformidade do conteúdo, resistência a dobras, índice de intumescimento, estudo de liberação da droga in vitro, teste in vitro para mucoadesão e estudos in vivo (teste de irritação da mucosa primária e atividade analgésica). Resultados: Todas as formulações apresentaram bons resultados para caracterizações físico-químicas. Em estudo de libertação de droga in vitro, os filmes exibiram liberação controlada por mais de 12 horas. A formulação de BFT2 (com quitosana e PVP K-90) não mostrou efeito irritante sobre a mucosa bucal e provocou uma atividade analgésica significativa in vivo com 57,14% de analgesia versus a do padrão (61,04%). Concluiu-se que os filmes mucoadesivos de cloridrato de tramadol podem ser usados eficazmente para aliviar a dor intensa de lesões ortopédicas com início rápido e ação prolongada.