Tissue engineering is an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function. By combining scaffolds, cells, and biologically active molecules, tissue engineers are developing therapeutic solutions for conditions where tissue failure or injury commonly occurs.
Stem Cells and Scaffolds in Tissue Engineering
One of the primary building blocks of Tissue Engineering is stem cells. Stem cells have the potential to both self-renew and differentiate into various cell types that make up tissues and organs. Tissue engineers have been exploring different types of stem cells, including embryonic stem cells, induced pluripotent stem cells, and adult stem cells isolated from tissues like bone marrow, fat, and skin. By seeding scaffolds with stem cells and exposing them to appropriate biological signals, stem cells can be differentiated into cells that make up tissues like bone, cartilage, muscle, and neural tissues.
Along with stem cells, scaffolds or templates provide the structural support and environment for tissues to regenerate. Scaffolds can either be natural or synthetic in nature. Natural biomaterials used frequently as scaffolds include collagen, fibrin, and polysaccharides derived from the extracellular matrix. Synthetic biomaterials like polyglycolic acid, polylactic acid, and polycaprolactone are also commonly used based on desired mechanical and degrading properties. Porosity, pore interconnectivity, mechanical properties, and surface properties are some of the key parameters considered when designing ideal tissue engineering scaffolds.
Tissue-Engineered Skin and Skin Substitutes
One of the most successful applications of tissue engineering has been in developing skin substitutes for treating burns and chronic wounds. Commonly used skin substitutes contain various combinations of fibroblasts, keratinocytes, collagen, proteins and growth factors in a matrix. Some examples include cultured epidermal autografts, biosynthetic dressings, and acellular human cadaver allografts. These temporary skin substitutes help protect wounds from further damage and infection while facilitating native tissue regeneration underneath. Permanent skin substitutes that completely replicate functional layered skin are also being explored using tissue-engineered skin constructs seeded with skin cells on scaffolds.
In recent years, companies like Organogenesis have also broughtbioengineered skin products like Apligraf® to the market. Thesebilayered skin substitutes combine keratinocytes and fibroblasts on abiodegradable scaffold for faster wound closure. Tissue engineering approaches are thus providing clinically proven solutions for treating some of the hardest healing skin wounds. Researchers continue developing better skin substitutes with long-term stability, biomechanical properties, vascularization and ability to form glands and hair follicles for aesthetic outcomes.
Advances in Tissue-Engineered Bone and Cartilage
Two other tissues where significant progress has been made using tissue engineering approaches are bone and cartilage. For bone regeneration, tissue engineers commonly employ bone marrow-derived mesenchymal stem cells (MSCs) combined with three-dimensional scaffolds made of materials like hydroxyapatite, beta-tricalcium phosphate, and composites. When cultured in appropriately osteoinductive conditions, MSCs can differentiate down an osteoblastic lineage and produce new bone tissue. Such tissue-engineered bone grafts have been used extensively in oral/maxillofacial reconstruction and treatment of non-union fractures.
Several biodegradable polymer-ceramic scaffolds seeded with chondrocytes or MSCs are also in clinical trials for cartilage repair and regeneration. Cartilage defects are challenging to treat given its avascular nature that limits healing. Tissue engineering strategies aim to recreate the zonal organization and biomechanical properties of healthy cartilage. Strategies involving chondrocyte implantation on scaffolds, use of growth factors to aid cartilage formation and stem cell-based approaches hold promise to regenerate durable and functional cartilage tissue. Overall, tissue engineering is providing alternatives for reconstructing bony and cartilaginous tissues that were limited earlier.
Cardiac and Neural Tissue Engineering
While challenges still remain, progress is gradually being made in engineering more complex tissues like cardiac and neural tissues as well. For heart disease, engineered heart tissues holding cardiomyocytes are being studied to regenerate heart muscle after injury. 3D bioprinting techniques are enabling precise spatial patterning of cardiomyocytes, endothelial cells and fibroblasts to better mimic native cardiac tissue architecture. Efforts are also underway to develop implantable cardiac patches biointegrating with host myocardium for treating conditions ranging from congestive heart failure to myocardial infarction.
In the realm of neural tissue engineering, researchers are utilizing scaffolds patterned with ECM proteins and surface cues to promote guided neural stem/progenitor cell differentiation. Hydrogels incorporated with neurotrophic factors are being optimized for application in spinal cord injury therapies. Others are exploring the regenerative capacity of Schwann cells, olfactory ensheathing cells and stem cell-derived neural progenitors to reconnect injured axons in the central nervous system. While the complexity of the brain and connections remain a big challenge, ongoing advancements are bringing us closer to engineering functional neural circuits and tissues.
Over the past few decades, tissue engineering has demonstrated significant potential to generate biological substitutes that restore or maintain tissue function. From lab-grown skin grafts to tissue-engineered blood vessels and cartilage implants already commercially available, applications of this field continue expanding. By combining advances in fields of biomaterials, stem cell biology, developmental biology, and translation, the future promises engineered versions of more complex tissues and whole organ fabrication. Despite persisting technical challenges, further advancements in this multidisciplinary field offer hope to treat conditions previously beyond reach.
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