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3 Types of Tissues
Epithelia, Basement Membrane and Connective Tissue (Make up almost all organs)
Epithelia
Epithelial layer covers all surfaces, tubes, and cavities of the body
Avascular (no blood vessels)
No significant amount of extracellular matrix (ECM). The ECM is the extracellular part of tissue
100% cells
Can regenerate spontaneously (ex. the epidermis in skin)
Avascular
No blood vessels
Basement Membrane
Acellular, avascular, continous layer of ECM separates the epithelial layer and the connective tissue
No cells, no blood vessels, 100% matrix
Regenerates spontaneously on the connective tissue
Connective Tissue
Cellular, contains ECM, heavily vascularized, and provides a reservoir for nutrient uptake to and waste removal from basement membrane and epithelia
Has cells, matrix, and blood vessels
Has limited ability to regenerate spontaneously (ex. dermis in skin)
Regeneration vs. Repair
Microscopic defects in connective tissues can regenerate with or without being treated by pharmaceuticals, vitamins, hormones and antibiotics
Organ-scale defects (large defects, mm or cm-scale) in connective tissues caused by disease or by an acute or chronic insult can’t regenerate
Adult mammals don’t typically exhibit spontaneous regeneration after severe organ injuries
Adult mammals undergo repair following severe organ injuries—closure of the wound by cell-mediated contraction and scar tissue formation
Regeneration
The synthesis of a physiological (normal, functional) replacement rissue in the wound site that’s structurally and functionally similar to the original tissue. Some connective tissues have capability to regenerate themselves, like skin, and some can’t effectively regenerate, like the heart. Some connective tissues that can self regenerate can’t effectively regenerate because it takes a long time, is a larg defect, a scar, etc.
Autograft
Tissue harvested from one location of the patient’s body and transplanted into another part of the same patient
Allograft
Tissue or organ harvested from donor and then transplanted into the patient
Xenograft
Tissue or organ from an animal is transplanted into a human recipient
Man-made Implants
Replacement of tissue with implants to replicate, augment and extend functions performed by biologoical systems.
Examples: Artifiical hearts, heart valves, prosthetic joints, and breast implants
Tissue Engineering/Regenerative Medicine
A multidiscipinary field involving the life, physicial and engineering sciences that seeks to develop functional cell, tissue, and organ substitutes to repair, replace or enhance biological function that has been lost due to congenital abnormalities, injury, disease, or aging.
OR
An interdisciplinary field that applies the principles of engineering and the life sciences towards the development of biological substitutes that restore, maintain or improve tissue function.
Tissue Engineering Strategies
(Paper Notes)
Cells + Biomaterials → Tissue → Implantation
Cells + Biomaterials → Implantation
Cells → Implantation
Biomaterials → Implantation
Tissue Regeneration Elements
Scaffold: Structural and mechanical support for cells
Cell: Source, cell type (cells can’t assemble by themselves to become the desired tissue)
Regulators: Growth factor (regulates cell behavior such as division), mechanical loading (mechanical stimuli; should have similar properties as the native tissue)
Scaffold
The structural and mechanical support for cells (typically are 3D since most tissues are 3D). Must have sufficient mechanical properties for proper support (should have the exact same mechanical properties as the tissue being engineered).
Roles of Scaffolds
Serve as a matrix for cell adhesion to facilitate or regulate cellular processes such as growth, migration (most cells need to attach to a matrix in order to survive since they normally adhere to the ECM)
Maintain the shape of the defect and prevent distortion of surrounding tissue
Serve as a barrier to the surrounding tissue that may impede the process of regeneration
Serve as a delivery vehicle for cells, growth factors and genes
Facilitate cell-matrix interactions that are involved with tissue regeneration by providing the appropriate sites for cell interaction
Growth factors/genes can be loaded into the scaffolds (how they can be used for cells)
Scaffolding Materials
Inorganic Materials: Ceramics and Bioglass
Synthetic Polymers (are organic but man-made): Polyesters and Polyurethanes
Natural Polymers (organic): Collagen, Albumin, Cellulose (most abundant natural polymer’ found in tress), and Chitosan (derived from chitin, 2nd most abundant natural polymer)
Collagen
Type 1: Most abundant type in the skin and throughout the body
Type 2: More localized
Ratio between the two vary depending on the tissue
Scaffold Types
Hydrogel (used because has similar characterisitcs to tissue)
Decellularized Tissue (gets rid of the risk of an immune response happening → risk is slim)
Porous scaffold (cells can proliferate, grow, and migrate into other pores
Core Scaffold Properties for Tissue Regeneration
Mechanical properties
Pore size, pore geometry, and pore size distribution (all three are equally important for the scaffold). The pores should be highly interconnected to allow for easy cell migration.
Interconnectivitiy and porosity (% of void space)
Cell/scaffold interactions (scaffold surface properties)
Controlled release of active molecules
Biodegradation (rate, mechanics vs time, cytocompatibility). [Slowly degrades overtime till whole tissue is regenerated, if too fast, leads to gaps, too slow leads to delayed regeneration)