Tissue Engineered Scaffolds for an Effective Healing and Regeneration: Reviewing Orthotopic Studies

Table 1

Function and macroscopic structure of tissues and organs here considered, along with histological features and expected characteristics that an ideal tissue engineered substitute should provide for regeneration.

Organ	Function	Structure	Histological features	Ideal scaffold properties
Trachea	Conduction of air from the nose or mouth to the lungs	Thin-walled, fibromuscular, airtight tube supported by C-shaped, cartilaginous rings, spans by the pars membranacea (fibroelastic ligament).; At its distal end, it bifurcates into the two main stem bronchi.	(i) Cartilaginous structure prevents collapse during respiration, provides flexibility, assures lumen patency; (ii) muscular tissue reduces lumen size during the cough reflex, facilitates airway clearance; (iii) mucosal membrane allows air conditioning, prevents epithelium dehydration	(i) lateral rigidity; (ii) longitudinal flexibility; (iii) impermeability to liquid and air; (iv) ability to induce functional ciliated respiratory epithelium resurfacing; (v) ability to induce blood vessel formation
Larynx	Orchestrate swallowing, breathing, coughing, and voice; Immunological organ	Tuned sphincter situated in the anterior portion of the neck	Mucosa-covered collection of cartilaginous framework (three single and two paired cartilages), ligaments, muscles, and vocal cords (covered by respiratory epithelium)	(i) whole laryngeal framework; (ii) low immunogenicity
Esophagus	Secretion of mucus to aid ingesta passage from the larynx to the stomach; Move of ingesta to the stomach through peristaltic movement	Muscular tube	(i) Mucosa: basal membrane consisting of nonkeratinized squamous epithelial cells, which produce the mucus.; (ii) Submucosa loose connective tissue (collagen types I and III, arranged in a criss-cross pattern), consisting of blood vessels and mucus glands.; (iii) Muscularis externa: contains inner circular and outer longitudinal muscle cells (skeletal and smooth).; (iv) Adventitia: composed of loose soft connective tissue, blood and lymph vessels, adipose tissue, and simple squamous cell epithelium	(i) tubular morphology and specific nanogeometry (four layers with different properties); (ii) resistant the reflux of gastric juice from the stomach; (iii) appropriate mechanical properties (strength and viscoelasticity) to withstand peristaltic movements
Heart valves	Guarantee the unidirectional blood flow within the beating heart	Situated around a tendinous ring, possess three cusps, except for the mitral valve, only two.	Distinct complex layers composed of interstitial fibroblasts and connective tissue fibres and lined by valvular endothelial cells: (i) ventricularis composed of mainly aligned elastic fibers (assist valve leaflet dynamics); (ii) spongiosa consists mainly of proteoglycans and glycosaminoglycans (to absorb shear stress during cyclical valve motion); (iii) fibrosa composed of mainly collagen (provide strength and stiffness to maintain coaptation in the diastolic phase)	(i) highly specialized three-dimensional (inhomogeneous) microstructure; (ii) anisotropic mechanical properties; (iii) dynamic behavior
Vascular system (blood vessels)	Blood transport through the body	Fibromuscular tubular structure	Three layers (from the lumen outward): (i) tunica intima composed of an endothelial cell monolayer (diffusion of oxygen and carbon dioxide); (ii) tunica media composed of smooth muscle cells (regulate blood flow by altering vascular resistance through vasoconstriction and vasodilatation); (iii) tunica adventitia composed of fibroblasts and elastic connective tissue (stretches and supports blood vessels)	(i) longitudinal and transversal elasticity; (ii) patency; (iii) impermeability to liquid and air; (iv) resistant to bacterial colonization; (v) thrombotic formation resistance
Kidney	Maintain body homeostasis by excreting excess water, regulating the chemical blood composition, removing waste products, and assuring endocrinologic functions	Bean-shaped structure made of approximately 0.5–1 million nephrons, consisting of a glomerulus, surrounded by a Bowman’s capsule, a proximal tubule, a loop of Henle, and a distal tubule connected to a collecting duct	Composed of various different cell types, including parietal cells, podocytes, tubule brush border cells, capillary bed covered by visceral epithelial cells, endothelial cells, and basement membrane (collagen IV, laminin, and heparin sulfate proteoglycans)	(i) provide blood ultrafiltration; (ii) provide transport regulatory function; (iii) appropriate mechanical properties (strength and viscoelasticity) to withstand peristaltic movements
Bladder	Store urine at low pressure and allow voluntary micturition, acting as a pressure vessel subjected to mechanical stress	Musculomembranous sac	(i) adventitia: connective tissue; (ii) muscular layer: inner longitudinal, circular, and outer longitudinal layers of thick muscle bundles with intrafascicular connective tissue; (iii) submucosa or lamina propria: connective tissue (collagen I, III, elastic fibers); (iv) mucosa: transitional epithelium (polyhedral flattened or large club-shaped cells), urothelial cells, and connective tissue (collagen IV and laminin); (v) serosa: simple squamous epithelium overlying connective tissue	(i) allow for even and constant attachment of mature epithelial cell layer on the luminal surface and harbor multiple cell layers of smooth muscle cells on the outside; (ii) provide adequate mechanical; support; (iii) prevent collapse prematurely before new tissue in vivo formation
Urinary tracts	Propel urine from the kidneys to the bladder (ureters) and from the bladder to the outside of the body (urethra)	Narrow fibromuscular tubular structure
Skeletal muscle	Locomotion, maintenance of posture, respiration (diaphragm and intercostal), communication, and production of body heat.	Composed of muscle cells (fibers), connective tissue, blood vessels, and nerves.	Muscle fibers form a long multinucleated syncytium grouped in bundles surrounded by connective tissue sheaths and extending from the site of origin to their insertion.; Connective tissue covering: (i) epimysium: dense connective tissue ensheathing the entire muscle; (ii) perimysium: surrounding bundles of muscle fibers; (iii) endomysium: layer of reticular fibers and ECM surrounding individual muscle fibers.	(i) appropriate mechanical properties, such as contraction, stiffness, force, and elasticity; (ii) provide orientation fiber guiding; (iii) provide adequate porosity