Table 2.

Epithelialisation of tissue-engineered scaffolds.

Organ	Scaffold Type	Source of the Cell	In vitro/species	Degree of epithelialisation	Comments	References
Trachea	Decellularised	Autologous bone marrow–mesenchymal stem cells	Human	Patient’s endoscopy 15 months after surgery showed complete epithelialisation	Inflammation after transplant. Epithelialisation took over 1 year, and graft took 18 months to be mechanically stable but since has been operational	Elliott et al.6
Trachea	Fibrin gel	Respiratory epithelial cells	In vitro	Epithelial cell profileration and differentiation was adequate. Similar results to collagen-coated microporous membranes control	Fibrin can be produced from autologous cells. Clinical application possible using injection moulding technique: research is scalable. Collagen-coated surfaces proliferated faster than fibrin	Cornelissen et al.24
Trachea	Decorin + PCL + gelatin	Tracheal epithelial cells	In vitro	Electrospun meshes with decorin woven into the fibres. Cells spread over the surface of this scaffold and maintained their phenotype	The outcome is good, with decorin enhancing non-immunogenic response. In-vivo experimentation is needed	Hinderer et al.25
Oesophagus	Decellularised	Oesophageal epithelial cell	Rat	Squamous stratified epithelial cell layer forms after 11 days. Once implanted, minor inflammatory response and angiogenesis in graft	There is some inflammatory response when using this scaffold, although not severe	Bhrany et al.26
Oesophagus	1. PCL 2. SF 3. PCL + SF Repeated with BM protein attachment	Oesophageal epithelial cell	In vitro	SF–enhanced epithelial cell attachment and proliferation when combined and individually. This was improved by basement membrane (BM) protein attachment	Important result as supports the idea that basement membrane proteins are essential to epithelial regeneration	Lv et al.27
Oesophagus	PCL and PCL–gelatin	Human oesophageal epithelial cells	In vitro	PCL–gelatin compound showed higher proliferation of cells to scaffolds although proliferation is seen on both	No clear stratification of oesophageal cell layers or squamous morphology formation	Kuppan et al.28
Oesophagus	PLGA scaffold precoated with collagen type VI	Canine oesophageal epithelial cells	In vitro and abdominal cavity of dog	‘Cobblestone-shaped morphology’ and presence of cytokeratins characteristics of epithelial cells: cell maintained oesophageal morphology over 4 weeks	PLGA is often deemed too expensive for wide use. Canine studies may have limited translatability to human models	Bao et al.29
Oesophagus	1. AlloDerm (decellularised skin scaffold) 2. PLLA 3. PLGA 4. PCL Repeated with collagen precoating	Rat oesophageal epithelial cells	In vitro	AlloDerm showed comparatively better epithelialisation when compared with synthetic models. There was faster monolayer formation, stratification and keratinisation	At lower calcium concentrations, there is increased proliferation; at higher calcium concentrations, there is increased differentiation. The pore size of synthetic scaffolds limited the formation of continuous epithelial layers	Beckstead et al.30
Oesophagus	1. Chitosan 2. Chitosan + fibronectin 3. Chitosan + elastin	Oesophageal epithelial cells	In vitro	Cells fail to adhere to chitosan only and chitosan + elastin. Chitosan + fibronectin formed strong adhesion contacts followed by de-adhesion	Long-term adhesion of cells is triggered when extracellular proteins such as fibronectin and chitosan polymer are present	Feng et al.31
Stomach	PGA mesh coated with PLLA	Stomach epithelium organoid units	Rat	H&E staining showed presence of gastric epithelial cells	The use of organoid units limited full analysis of epithelialisation. There is also focus on patch formation rather than organ replacement	Maemura et al.1
Bladder	Decellularised	Human bladder cells	In vitro	Urothelial cells proliferated on scaffold but were poorly attached	Basal lamina maintained may improve epithelial cell attachment. This decellularisation protocol may be restricted to thinner, less-dense scaffolds with loose collagen arrangements	Rosario et al.32
Bladder	Decellularised	Canine bladder cells	Rat	Urothelium adhered and proliferated on scaffold, forming a multi-layered structure with positive cytokeratin result	Good result	Han et al.33
Urethra	PLLA	Rabbit urothelial cells	In vitro	Good adhesion and proliferation of urothelial cells to scaffold, which had been modified with non-knitted filaments	In-vitro study cannot evaluate how the scaffold copes with in-vivo biophysical stresses. Exposure to urine and genitourinary compounds may affect the cell viability which cannot be deduced from this study	Fu et al.34
Urethra	Decellularised bladder matrix	Mesothelial cells	Rabbit	Grafts placed in rabbit were covered with loose collagen matrix. No stricture formation and multilayer urethral architecture by 1 month	Good outcomes, but restricted to biological models	Gu et al.35
Urethra	Gelatin sponge	Porcine buccal mucosal cells	Pig	Gelatin sponge was partially absorbed, complete epithelialisation of the implant was seen after 1 month. However, there was inflammation and epithelium degenerated after 2 months	The degeneration of the mucosa is not ideal. The environment of the urethral epithelium needs to be examined to determine challenges to epithelial cell survival	Li et al.36

PCL: polycaprolactone; SF: silk fibroin; PLGA: poly(lactic-co-glycolic) acid; PLLA: poly(lactic acid).