Razi Journal of Medical Sciences

fa نقش بیوراکتورها در مهندسی بافت غضروف: یک مطالعه مروری The role of bioreactors in cartilage tissue engineering: A review study بیولوژی (زیست شناسی) Biology مروري review article یکی از مهم‌ترین اهداف مهندسی بافت غضروف، ایجاد و توسعه ایمپلنت‌های غضروفی در شرایط آزمایشگاهی است که پس از پیوند آن به محل آسیب‌دیده غضروفی، خواص غضروف طبیعی را نشان دهند. سه ترکیب اصلی مهندسی بافت غضروف شامل منبع سلولی ازجمله کندروسیت‌های اتولوگ گسترش یافته در محیط آزمایشگاهی و پیش‌سازهای مزانشیمی، داربست‌های زیستی که روی آن سلول‌ها کشت می‌شوند و بیوراکتور است که تلاش می‌کند تا شرایط فیزیکی و شیمیایی واقع در بدن موجود زنده را که در آن غضروف قادر است رشد نماید، بازسازی کند. اگرچه پیشرفت‌های زیادی در راستای توسعه ساختارهای غضروفی مفید جهت شرایط بالینی حاصل شده است، با این حال، ساختارهای غضروفی تولید شده فعلی، خواص فیزیکوشیمیایی نامناسب‌تری را نسبت به غضروف طبیعی نشان داده‌اند. یکی از دلایل این معضل، عدم توجه به نیروهای مکانیکی در کشت سلول غضروفی است. بیوراکتورها به‌عنوان وسیله‌ای تعریف می‌شوند که در آن‌ها فرایندهای بیولوژیکی یا بیوشیمیایی می‌توانند تحت شرایط کنترل شده‌ای، قرار گیرند. به‌عنوان مثال می‌توان پارامترها و شرایطی همچون pH، دما، عرضه مواد مغذی، تنش O2 و حذف مواد زائد را کنترل نمود. هدف این مطالعه، مطالعه نقش بیوراکتورها در مهندسی بافت غضروف، و بررسی برخی از مطالعات آزمایشگاهی و پیش بالینی انجام شده در زمینه مهندسی بافت غضروف با استفاده از بیوراکتور می‌باشد.  One of the most important aims of cartilage tissue engineering is the in vitro creation and development of cartilage implants, which, after transplantation to the damaged site, show the properties of normal cartilage. The three major combinations of cartilage tissue engineering include: cellular sources, consisting of autologous chondrocytes developed in the laboratory and mesenchymal precursors; biomaterials upon which the cells are cultivated; and a bioreactor that tries to rebuilds the physical and chemical characteristics of the in vivo system, which allows the cartilage to grow in it. Although much progress has been made towards developing cartilage structures for clinical conditions, nevertheless, current cartilage structures have inappropriate physicochemical properties, compared to normal cartilage. One of the reasons for this problem is the lack of attention paid to mechanical stimuli in cartilage cell culture. Several mechanisms can be involved in chondrocyte response into mechanical stimuli, including alteration of serum level of oligomeric matrix protein, alteration of expression of cartilage-specific genes (collagen type 2 and aggrecan), that leads to organizes the rearrangement of collagen, integrin, and glycosaminoglycan binding. Other mechanisms also include altered integrin expression and induction of apoptotic mechanisms. Several mechanical forces such as tensile and compressive forces regulate chondrocyte production.  Bioreactors are designed to enhance the biochemical and mechanical properties of cartilage tissue and to transfer sufficient volume and mechanical stimulation of cartilage tissue. Bioreactors are defined as a means in which biological or biochemical processes can occur under controlled conditions. For example, several parameters and conditions, such as pH, temperature, nutrient supply, O2 stress, and waste removal, can be controlled by the bioreactor. Various bioreactor systems, including rotating-wall vessels, spinner-flasks, direct perfusion bioreactors, compressor bioreactors, magnetic bioreactors, ultrasonic bioreactors and stirrer double chambers, have been used in cartilage tissue engineering. In addition, existing bioreactors were used in combination with other emerging technologies. For example, 3D-Printed (3DP) Bioreactors were used for cartilage tissue engineering. Furthermore, bioreactors using microcarriers were another strategy which used for cartilage tissue engineering. Additionally, bioreactors that use combined mechanical force are also among the bioreactors that are being developed in cartilage tissue engineering. Over the past few decades, fluid flow bioreactors (shear pressures) have been widely used in cartilage tissue engineering. The rotating wall vessel is a specialized cell culture vessel developed initially as a microgravity simulator to mimic and model the effects of microgravity on cells in laboratory studies. The vessel creates low-shear culture environments and supports three-dimensional tissue development. It has a motor that drives a belt that rotates the cylindrical culture vessel along its horizontal axis. It contains an air pump, which draws incubator air through a filter and discharges the air through a rotating coupling on the shaft that carries the vessel. Spinner-flask bioreactor alternatives to the static culture that attempt to reduce gradients in metabolite and nutrient concentrations. Perfusion systems are the most complex because they can perfuse fluid directly via the structures, making good mass transport inside the constructs, and they have been shown to overexpress the expression of chondrocyte markers. compressor bioreactors are another type of bioreactor which use compression force to modulate the behavior of cells in tissue or scaffold. magnetic bioreactors are a type of bioreactors which are based on microscale mechanobiological techniques such as magnetic forces. these bioreactors can influence on cells, tissues, and entire organisms, including the hyaline cartilage synthesis, bovine chondrocytes proliferation, and the proteoglycan formation. Ultrasonic stimulation is another parameter which could affect cell growth in some cases. Specially, low-intensity continuous ultrasound (US) has been demonstration to regulate the expression of chondrocyte-specific genes. Ultrasonic bioreactors are a type of bioreactors which are based on ultrasonic stimulation. Another bioreactor used in cartilage tissue engineering is hydrostatic pressure bioreactors. These bioreactors have been shown to have the ability to dramatically increase cartilage formation. Hydrostatic pressure can be applied to culturing monolayer cells on the dish by covering the cultured cells with the culture medium and placing them in a pressure chamber (where a pressure step is applied to both sides of the dish). Hydrostatic pressure bioreactors consist of fluid-filled chambers connected to a water pump. In these bioreactors, the tank is completely filled with water and a sealed syringe is placed at the bottom. The syringe contains the culture volume with the sample. The water pump squeezes the water into the container and, as a result, moves the syringe and applies hydrostatic pressure to the transfer culture volume. Significantly, recent studies have shown that constant hydrostatic pressure is more efficient on cartilage cells in three-dimensional culture. Another bioreactor used in cartilage tissue engineering is compression bioreactors. These bioreactors cause dynamic pressure loading, which is similar to the physiological loading that normally occurs in cartilage. Compression bioreactors can improve mass formation and modulate flexible cartilage formation similar to the approach that occurs in natural cartilage. Furthermore, static and perfused bioreactors are two other bioreactors used for cartilage tissue engineering. Spinner-flask bioreactors have shown high efficiency in cartilage regeneration and this regeneration has been confirmed by PCR and histological analysis. Chondrocyte cultured in injectable bioreactors increased viability and produced cartilage uniformity that had biomechanical properties similar to normal cartilage tissue. Structures cultured in perfusion-compression bioreactors showed higher cell proliferation and better structural integrity compared to stable conditions. In general, the use of bioreactors has led to improvements in terms such as the glycosaminoglycan (GAG) quantification and relevant gene expression and matrix secretion, extracellular matrix synthesis, collagen II synthesis, changed expression integrin, cell proliferation, migration, apoptosis and viability, and gene expression of specific-chondrocytes markers, chondrogenic differentiation, cartilage formation, recovery and retain functional joint surface, hyaline cartilage formation, compression modulus, biosynthetic activity of osteoarthritic chondrocytes and metabolic activity in cartilage tissue engineering. Bioreactors are used in standard conditions such as pH and oxygen stress, which are important in the reproducibility of biological batches. However, much discussion remains regarding the specific function of various mechanical stimuli. Findings from case studies have shown that bioreactors will also be effective in providing the necessary conditions for further study on these stimuli. There are now new ideas in the use of bioreactors, such as bioreactor in vivo, which is hoped to provide cartilage engineering in vivo.   <h3></h3> بیوراکتور, مهندسی بافت, غضروف, مطالعه مروری Bioreactor, Tissue Engineering, Cartilage, Review Study 50 66 http://rjms.iums.ac.ir/browse.php?a_code=A-10-4369-2&slc_lang=fa&sid=1 Hamed Manoochehri حامد منوچهری manoochehry.hamed@gmail.com 3900319475328460061703 3900319475328460061703 No , Hamadan University of Medical Sciences, Hamadan, Iran دانشگاه علوم پزشکی همدان، همدان، ایران Naser Kalhor qom ناصر کلهر قم naserkalhor@gmail.com 3900319475328460061704 3900319475328460061704 No Department of Mesenchymal Stem Cell, The Academic Centre for Education, Culture and Research, Qom, Iran. گروه سلول های بنیادی مزانشیمی، جهاد دانشگاهی قم، قم-ایران. Hamid Tanzadehpanah حمید تن زده پناه h.tanzadehpanah@gmail.com 3900319475328460061705 3900319475328460061705 No Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. مرکز تحقیقات پزشکی مولکولی، دانشگاه علوم پزشکی همدان، همدان، ایران. Mohsen Sheykhhasan محسن شیخ حسن mohsen.sh2009@gmail.com 3900319475328460061706 3900319475328460061706 Yes Hamadan University of Medical Sciences, Hamadan, Iran, & Department of Stem Cell, the Academic Centre for Education, Qom Branch, Qom, Iran دانشگاه علوم پزشکی همدان، همدان، ایران؛ گروه سلول‌های بنیادی مزانشیمی، جهاد دانشگاهی قم، قم، ایران