Table 1.

Summary of key challenges and recent strategies regarding islets encapsulation.

Key challenges	Strategies	Methods
Acute hypoxia	Hypoxia preconditioning	–Islets pre-exposed to intermittent hypoxia [358].
		–Islets preconditioned in carbon monoxide gas [465], [466].
	Oxygen-releasing molecules	–Perfluorocarbons (PFCs) [369].
		–Calcium peroxide (CPO) [372], [373], [374].
		–Hemoglobin (Hb) [377], [378], [379].
	External oxygen supply	–β Air device (oxygen refueling technique) [467].
		–Oxysite (encapsulation of CPO within polydimethylsiloxane) [334].
		–Subcutaneously transplanted islets followed by 50 % oxygen inhalation treatment [468].
Chronic hypoxia	Pre-vascularization	–Pre-implantation an agarose rod containing cyclic oligopeptide SEK-1005 [277].
		–Pre-implantation of FGF-releasing collagen-based sheet [414].
		–‘Device-less’ transplant technique [220], [451], [452].
	Re-vascularization	–Delivery systems for growth factors VEGF [336], [401] or FGF [410], [411], [413]. –Co-transplantation of bone-morrow or adipose mesenchymal stem cells (MSCs) with encapsulated islets to improve angiogenesis [469]. –Coating 1,12-dodecanedioic acid (DDA) on a chitosan pouch [273]. –Co-transplantation with accessory cells such as endothelial progenitor cells [184], [186], [187].
Foreign body response	Immunoisolation	–Polyacrylonitrile and polyvinyl chloride copolymers (PAN/PVC) [470], [471]. –Polyurethane and polyvinyl pyrrolidone copolymers (PU/PVP) [472], [473]. –Polytetrafluoroethylene (PTFE) membranes [474], [475]. –Triazole thiomorpholine dioxide (TMTD)-modified alginate encapsulation [476]. –Co-incorporation of islets and Tregs in PLGA scaffolds [200]. –Silicon [477]. –Aluminum/aluminum oxide (Al/Al2O3) [478], [479]. –Electrical charges modification [251], [480].
	Implant topography modification	–Avoid sharp edge [251].
		–Surface roughness [214].
		–Modification of the size of spherical implants in a certain range [260].
	Anti-fouling materials	–Zwitterionically modified alginates [267].
	Coating techniques	–Coating 1,12-dodecanedioic acid (DDA) on a chitosan pouch [299].
		–Coating PEG/alginates around the islets [481], [482].
		–Rapamycin-PEG coated alginate microsphere [483].
	Delivery system for immunomodulatory cells and immunomodulators	–PLGA scaffolds with controlled release of TGF-β1 [423].
		–Co-incorporation of islets and Tregs in PLGA scaffolds [200].
		–Islets encapsulated within PEG containing a crosslinked hemoglobin [484].
		–Treatment of immunomodulatory agents after islet transplantation (e.g. cyclosporine and dexamethasone) [485].
		–New immunosuppressive treatment (CTLA4-Ig combined with anti-CD154 mAb treatment) on nonobese diabetic mice transplanted with alginate-encapsulated islets [486].
		–Co-encapsulation of CXCL12 and islets in alginate capsule can recruited Treg cells to suppress T-cells function [487].
		–Co-encapsulation of tacrolimus-loaded PLGA microspheres and islets in a hydrogel [488].
		–Co-encapsulation of TLR2-modulating pectin polymers and alginate in a microcapsule [489].
		–Co-transplantation of Fas ligand with streptavidin (SA-FasL) microgels and islets [490].
	Robotic drug delivery technique	–Dynamic Soft Reservoir (DSR) that utilized mechanical oscillation to mitigate fibrotic capsule formation [224], [491].