Cartilage Tissue Engineering –Our Recent Experiences

Prabha D Nair
Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum, India

Damage to cartilage, caused either by injury or age, affects a large number of people worldwide, severely reducing the patients’ quality of life and generating a huge burden on healthcare systems. Diseases such as osteoarthritis, trauma, chondrosarcoma and other congenital abnormalities are likely to lead to defective cartilage and the need of requirements for replacement therapies. Current clinical therapies include cartilage transplantation or implantation of prosthesis made of artificial materials, which have their own limitations. Tissue engineering of cartilage is a revolutionary addition to the therapeutic armamentarium of medical approach to the treatment of cartilage defects. An appropriate scaffold, chondrocytes, signaling molecules and culture conditions are required to produce functional tissue engineered cartilage.

The success of a tissue engineering approach is highly dependent on the properties of scaffolds like 3D structure, biocompatibility, optimum degradation rate, nontoxic degradation products and good mechanical properties. The development of synthetic and naturally occurring scaffolds as extra cellular matrix (ECM) mimics for tissue engineering applications have included a variety of strategies to promote the attachment of specific cell types, control the rate of scaffold degradation, encourage cell proliferation, or otherwise modulate the host tissue response. Chondrocytes require a 3 dimensional support, during in vitro culture, similar to that of native ECM for adequate synthesis of typical matrix molecules like collagen and glycosaminoglycans. An interconnected porous scaffold, which offers sufficient mechanical stability to withstand the loads imparted by the cells during invitro culture and initial implantation, is imminently desirable. Porosity, pore structure, and pore size are important factors affecting the nutrient supply of transplanted cells. Additionally, the interconnected porous network effectively permits the diffusion of nutrients and waste materials from the scaffolds. Besides cell morphology, function of many cells depends on 3D spatial relationship of cells and matrix. Cellular activity can also be modulated by several stimuli such as grafting ligands on to scaffolds for specific interactions with cell surface receptors. The commonly used scaffolds like poly (lactic acid) and poly (glycolic acid) lack such specific ligands and produce acidic degradation products that are toxic to cells (1).

This talk focused on the work involving the fabrication of a biodegradable and tough, Poly (vinyl alcohol)-poly (caprolactone) Semi IPN scaffold that is suitable for cartilage tissue engineering. The synthetic strategy we have employed allows for easy control of mechanical and chemical properties of the matrix, and has synergistic properties of its constituent polymers. The hybrid scaffold is nontoxic and highly hydrophilic with greater absorptive capacity and is also amenable for further modification with bioactive peptides. Porcine chondrocytes seeded within the unmodified scaffolds secrete extra cellular matrix components revealing that the hybrid scaffold has immense potential for tissue engineering applications. In addition, we have also been able to differentiate mesenchymal stem cell to chondrocytes in these 3D scaffolds.

Orthoses for Assisting Regeneration of Cartilage in Knee Joints of Arthritis Patients.

H.T. Kashipara, Avani Shah, G.A. Motwani
Shree U.V. Patel College of Engineering, Ganpat University, Kherva, Mehsana-382711.

Old age adults are the commonly known patients of knee arthritis that produce walking, sitting and stair-climbing disabilities due to pain, joint stiffness and loss of joint movements. Because of calcium deficiency their femur and tibia of lower limbs undergo alignment anamolies normally femoral varus (inward lateral deviation) and tibial vagus (outward lateral deviation) types. These deformations cause the compression and shear force components of weight bearing at the knee joint considerably increase and stress the knee compartments. The studies reveal that 60% to 80% of the load is distributed over the medial compartment. The angulation deformity contributes to the progressive increase in the compressive and shear force components of the weight bearing at the medial compartment. The result is the damage to the articular semilunar cartilage and the condyloid bone area. The damage is in the form of stretching and rupturing of cartilage. The damage starts from one end of cartilage. This is the beginning of knee arthritis with symptoms of pain, tissue irritation and inflammation of the joint capsule.

The paper described the two types of orthoses tried by the authors for relieving stress on the medial compartment of osteoarthritis knee joint:

Wedge shaped Insole Orthoses in shoes: The wedge shaped full length insoles incline angle 5° made from shock absorbing and high resistive to compression deformation were fitted on the sides in comfortable light weight shock absorbing shoes. The clinical trial was performed on the author’s spouse Mrs. Anu Kashipara wearing 6 hours daily for 6 weeks. The results were quite affirmative with decreased pain while walking, sitting and stair-climbing.

Unloader Knee Orthoses: These Orthoses are designed and constructed to distract joint surfaces of medial compartment of the knee using three-point force system to unload the joint. A thrust type unloader orthosis with a unilateral poly axial hinge joining the thigh and calf components, and supported by a nylon force-strap was used. The nylon strap wrapped through popliteal area unloads the medial compartment by placing pressure over it. The clinical trial on several osteoarthritis patients of different age group with initial symptoms of knee arthritis was affirmative to reduce pain during walking, sitting and stair-climbing at Paraplegia Institute, Ahmedabad.

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