CÔNG NGHỆ SCAFFOLD ỨNG DỤNG TRONG CẤY GHÉP TẾ BÀO GỐC ĐIỀU TRỊ CÁC TỔN THƯƠNG CƠ XƯƠNG KHỚP

Scaffold là chất mang hay còn gọi là giá đỡ sinh học, hay giàn giáo sinh học, có vai trò quan trọng trong công nghệ cấy ghép tế bào gốc. Trong bài này chúng tôi xin giới sơ lược về scaffold, chất liệu, cấu trúc, các đặc tính của scaffold và cách tạo hình 3D scaffold

Fabrication of bioinspired grid-crimp micropatterns by melt electrospinning writing for bone-ligament interface study

Many strategies have been adopted to engineer bone-ligament interface, which is of great value to both the tissue regeneration and the mechanism understanding underlying interface regeneration. However, how to recapitulate the complexity and heterogeneity of the native bone-ligament interface including the structural, cellular and mechanical gradients is still challenging. In this work, a bioinspired grid-crimp micropattern fabricated by melt electrospinning writing (MEW) was proposed to mimic the native structure of bone-ligament interface. The printing strategy of crimped fiber micropattern was developed and the processing parameters were optimized, which were used to mimic the crimp structure of the collagen fibrils in ligament. The guidance effect of the crimp angle and fiber spacing on the orientation of fibroblasts was studied, and both of them showed different levels of cell alignment effect.. MEW grid micropatterns with different fiber spacings were fabricated as bone region. Both the alkaling phosphatase activity and calcium mineralization results demonstrated the higher osteoinductive ability of the MEW grid structures, especially for that with smaller fiber spacing. The combined grid-crimp micropatterns were applied for the co-culture of fibroblasts and osteoblasts. The results showed that more cells were observed to migrate into the in-between interface region for the pattern with smaller fiber spacing, suggested the faster migration speed of cells. Finally, a cylindrical triphasic scaffold was successfully generated by rolling the grid-crimp micropatterns up, showing both structural and mechanical similarity to the native bone-ligament interface. In summary, the proposed strategy is reliable to fabricate grid-crimp triphasic micropatterns with controllable structural parameters to mimic the native bone-to-ligament structure, and the generated 3D scaffold shows great potential for the further bone-ligament interface tissue engineering.

Blockade of glutamine-dependent cell survival augments antitumor efficacy of CPI-613 in head and neck cancer

Background Alterations in metabolism are one of the emerging hallmarks of cancer cells and targeting dysregulated cancer metabolism provides a new approach to developing more selective therapeutics. However, insufficient blockade critical metabolic dependencies of cancer allows the development of metabolic bypasses, thus limiting therapeutic benefits. Methods A series of head and neck squamous cell carcinoma (HNSCC) cell lines and animal models were used to determine the efficacy of CPI-613 and CB-839 when given alone or in combination. Glutaminase 1 (GLS1) depletion was achieved by lentiviral shRNAs. Cell viability and apoptosis were determined in HNSCC cells cultured in 2D culture dish and SeedEZ™ 3D scaffold. Molecular alterations were examined by Western blotting and immunohistochemistry. Metabolic changes were assessed by glucose uptake, lactate production, glutathione levels, and oxygen consumption rate. Results We show here that HNSCC cells display strong addiction to glutamine. CPI-613, a novel lipoate analog, redirects cellular activity towards tumor-promoting glutaminolysis, leading to low anticancer efficacy in HNSCC cells. Mechanistically, CPI-613 inhibits the tricarboxylic acid cycle by blocking the enzyme activities of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, which upregulates GLS1 and eventually promotes the compensatory role of glutaminolysis in cancer cell survival. Most importantly, the addition of a GLS1 inhibitor CB-839 to CPI-613 treatment abrogates the metabolic dependency of HNSCC cells on glutamine, achieving a synergistic anticancer effect in glutamine-addicted HNSCC. Conclusions These findings uncover the critical role of GLS1-mediated glutaminolysis in CPI-613 treatment and suggest that the CB-839 and CPI-613 combination may potentiate synergistic anticancer activity for HNSCC therapeutic gain.

Peningkatan Kualitas Kuat Tekan Produk Scaffold Hidroksiapatit (Ha)-Gelatin-Polivinil Alkohol (PVA) Menggunakan Metode Taguchi

Kerusakan tulang yang akan terjadi di Indonesia pada golongan tenaga kerja sebesar 67,76% berupa penurunan massa tulang dan sebesar 28,58% berupa gangguan kepadatan tulang. Scaffold dapat dijadikan sebagai alternatif dari perawatan penyembuhan kerusakan tulang dalam bentuk perancah berpori 3D. Scaffold dapat menyediakan lingkungan yang sesuai untuk regenerasi jaringan tulang. Biomaterial keramik sebagai bahan dasar yang cocok untuk scaffold karena karakteristiknya, namun memiliki kekurangan berupa elastisitas rendah dengan permukaan yang keras dan rapuh. Pada penelitian ini dilakukan penambahan material berupa biomaterial gelatin dan PVA yang mana sangat ideal untuk diferensiasi sel dan kekuatan mekanik dari scaffold. Dalam upaya memperbaiki kualitas produk dan proses pembuatan scaffold, desain eksperimen dengan Metode Taguchi untuk mengetahui parameter yang memberikan nilai kuat tekan yang sesuai dengan tulang manusia. Parameter proses yang digunakan yaitu rasio bubuk hydroxyapatite (HA), rasio bubuk gelatin, dan rasio bubuk polyvynyl alcohol (PVA). Berdasarkan hasil penelitian yang dilakukan parameter proses rasio bubuk hydroxyapatite (HA), rasio bubuk gelatin, dan rasio bubuk polyvynyl alcohol (PVA) sangat berpengaruh terhadap nilai kuat tekan scaffold. Hasil eksperimen konfirmasi diperoleh mean sebesar 3,287 MPa menunjukkan bahwa nilai kuat tekan scaffold berada pada rentan nilai kuat tekan manusia.

Ultrasound-triggered on Demand Lidocaine Release Relieves Postoperative Pain

BackgroundSafe and noninvasive on-demand relief is a crucial and effective treatment for postoperative pain because it considers variable timing and intensity of anesthetics. Ultrasound modulation is a promising technique for this treatment because it allows convenient timed and noninvasive controlled drug release.MethodsWe created an ultrasound-triggered lidocaine (Lido) release platform using an amino acid hydrogel functioning as three dimensional (3D) scaffold material (Lido-PPIX@ER hydrogel). Optimal preparation conditions and ultrasound-triggered parameters were evaluated. In the postoperative pain SD rat model, the Lido-PPIX@ER hydrogel or free lidocaine was administered by subcutaneous injection immediately after making the paw incision. Mechanical hypersensitivity was assessed using calibrated von Frey filaments after an individualized (highly variable) ultrasound-triggered process. The safety of the treatment was also evaluated.ResultsThe Lido-PPIX@ER hydrogel allows control of the timing, intensity and duration of lidocaine (Lido) to relieve postoperative pain. The hydrogel releases Lido due to the elevated reactive oxygen species (ROS) levels generated by PPIX under ultrasound triggering. The optimal ultrasound parameter (0.3 W/cm2, 30 s) was chosen for in vitro and in vivo studies. The Lido-PPIX@ER hydrogel (with lidocaine, 5.6 mg/mL) under individualized ultrasound triggering (every 2 h in the first 12 h, every 4 h for the next 36 h, and then every 6 h until 72 h postsurgery) released lidocaine and provided effective analgesia for more than 72 h. Additionally, the withdrawal threshold was higher than that in the control group at all time points measured. The hydrogel showed repeatable and adjustable ultrasound-triggered nerve blocks in vivo, the duration of which depended on the extent and intensity of insonation. On histopathology, no systemic effect or tissue reaction was observed in the ultrasound-triggered Lido-PPIX@ER hydrogel-treated group.ConclusionsThe Lido-PPIX@ER hydrogel with individualized (highly variable) ultrasound triggering is a convenient and effective method that offers timed and spatiotemporally controlled Lido release to manage postoperative pain.