基于可注射生物材料的干细胞移植通常使用水凝胶,因为水凝胶具有再现微环境的潜力。水凝胶通常通过物理或化学交联低聚物前体制成。利用二价钙离子和自组装肽(SAP)双亲化合物(PAs)进行离子交联的藻酸盐被广泛用于干细胞递送(Lee等人,2019年)。刺激响应性水凝胶,如热响应性聚N-异丙基丙烯酰胺(PNIPAAm)(Li et al、
生物材料在再生医学中的重要性日益明显。生物材料可以定制,以提供再生所需的生物物理和生物化学线索。生物材料还可用于进一步了解细胞与微环境的相互作用及其对干性、自我更新、血统承诺、细胞生理学和新陈代谢的影响(Abdeen and Saha, 2017; Chai and Leong, 2007)。换句话说,生物材料可用来为干细胞创造一个更好的家园。
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Zhao X, Li Q, Guo Z, and Li Z (2021)。利用生物材料支架构建干细胞治疗的细胞微环境。干细胞研究疗法》12,1-13。10.1186/S13287-021-02650-W/ FIGURES/5.[PubMed: 33397467] (英文)
Zheng M、Mitra RN、Weiss ER 和 Han Z(2020b)。视网膜色素变性模型中,Rhodopsin 基因组 DNA 纳米颗粒改善了视网膜变性的表达和挽救。Mol.Ther 28, 523-535.10.1016/j.ymthe.2019.11.031.10.1016/j.ymthe.2019.11.031. [PubMed: 31879189]
Zheng H, Tian Y, Gao Q, Yu Y, Xia X, Feng Z, Dong F, Wu X, and Sui L (2020a)。分层微纳形貌通过整合素 a2-PI3KAKT 信号轴促进细胞粘附和成骨分化。Front.Bioeng.Biotechnol 8, 463.10.3389/fbioe.2020.00463.10.3389/fbioe.2020.00463. [PubMed: 32509748].
Zhong J、Chan A、Morad L、Kornblum HI、Fan G 和 Carmichael ST(2010 年)。中风脑移植后支持干细胞存活的水凝胶基质。神经康复。神经修复》24,636-644。10.1177/1545968310361958.
Zhong Z, Deng X, Wang P, Yu C, Kiratitanaporn W, Wu X, Schimelman J, Tang M, Balayan A, Yao E, et al. (2021)。用于结膜下眼球注射的结膜干细胞微结构的快速生物打印。生物材料 267,120462。10.1016/J.BI0MATERIALS.2020.120462.[PubMed: 33129190] (英文)
Zhu M, Li W, Dong X, Yuan X, Midgley AC, Chang H, Wang Y, Wang H, Wang K, Ma PX, et al. (2019).具有定向组织再生指导性龛位的体内工程细胞外基质支架。Nat.Commun 10, 4620.10.1038/s41467-019-12545-3.[PubMed: 31604958].
nuew ıd!ıכsnuew ıOบłnท https://cdn.mathpix.com/cropped/2024_11_10_3ad04f7655f7ffbe4d46g-52.jpg?height=719&width=63&top_left_y=368&top_left_x=60
Targets Technologies/platforms Engineered biomaterials and cells Merits and outcomes References
templated (SMART) neurospheres
designer injectable gels shear-thinning hydrogel for injectable encapsulation and long-term delivery (SHIELD) hydrogels made from C7 protein, 8-arm PEG polymer modified with proline-rich peptides, and PNIPAAm for Schwann cell transplants increased Schwann cell survival and retention, significantly improved spatial distribution within endogenous tissue, reduced cystic cavitation and neuronal loss, and substantially increased forelimb strength and coordination (Marquardt et al., 2020)
glycomaterial implants acellular-engineered chondroitin sulfate (eCS) matrix with brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF-2) accelerated cellular repair and gross motor function recovery, enhanced volumetric vascularization, activity-regulated cytoskeleton (Arc) protein expression, and perilesional sensorimotor connectivity in chronic severe TBI (Latchoumane et al., 2021)
Wharton's Jelly scaffolds derived from human platelet lysate and human plasma fibrinogen with thrombin as a crosslinker and encapsulated with human mesenchymal stem cells (hMSCs) demonstrated high survivability, stable proliferation rate, migration out of the hydrogel, upregulated expression of neurotrophic factors, cytokines, and neural markers, and increased expression of neural differentiation markers (Lech et al., 2020)
Elastic ECM thin polyacrylamide substrates (PA), ECM with myelinating glia demonstrated inhibited branching and differentiation of oligodendrocytes (OLs) on rigid, lesion-like matrices whereas Schwann cells (SCs) developed normally in both soft and stiffer matrices to promote healing and regeneration in both CNS and PNS (Urbanski et al., 2016)
HYDROSAP hydrogels self-assembling peptides (SAPs) hydrogels with human neural stem cell (hNSC) decreased astrogliosis and immune response, increased neuronal markers, improved hNSC engraftment, enhanced behavioral recovery, and formation of 3D functional neuronal networks (Marchini et al., 2019)
brain stiffness-mimicking gel tilapia collagen gel with hiPSCs-derived dorsal cortical neurons demonstrated lineage commitment to the terminal neural subtype, improved neurogenesis and neural function, and enhanced production of dorsal cortical neurons (Iwashita et al., 2019)
thermosensitive hydrogels combined growth factors acellular spinal cord scaffold with bFGF and heparin-poloxamer (HP) for endogenous regeneration efficient inhibition of glial scars and improved functional recovery via regeneration of nerve axons and the differentiation of neural stem cells in the SCI (Xu et al., 2016)
photoresponsive neuroprotective protein hydrogel His6-tagged recombinant protein, SpyTag-ELP-CarHC-ELP-SpyTag (ACA), metal ions, and adenosylco-balamin with hMSCs and leukemia inhibitory factors (LIFs) showed excellent injectability, photodegradability, facile encapsulation and delivery of cells and proteins, prolonged cellular signaling, and enhanced axon regeneration (Jiang et al., 2020)
multichannel polymer scaffold PLGA scaffolds with activated Schwann cells and MSCs exhibited significant recovery of nerve function, enhanced differentiation into neuron-like cells, good colocalization with host neurons, and formation of robust bundles of regenerated fibers (Yang et al., 2017)
bioactive scaffolds with enhanced supramolecular motion library of IKVAV peptide amphiphiles with different sequences of amino acids V,A, and G (IKVAV PA1 to PA8) for endogenous regeneration intensified molecular motions within scaffold fibrils enhanced vascular growth, axonal regeneration, myelination, survival of motor neurons, and functional recovery with reduced gliosis (Álvarez et al., 2021)
growth facilitators diblock copolypeptide hydrogel K180L20 with FGF-2, EGF, GNDF for endogenous regeneration regrew full spinal segment beyond lesion centers into neural tissue with terminal-like contacts and displaying synaptic markers, improved electrophysiological conduction, and reinstated developmentally essential mechanisms to facilitate axon growth (Anderson et al., 2018)| nuew | ıd!ıכsnuew ıOบłnท | | ![](https://cdn.mathpix.com/cropped/2024_11_10_3ad04f7655f7ffbe4d46g-52.jpg?height=719&width=63&top_left_y=368&top_left_x=60) | |
| :---: | :---: | :---: | :---: | :---: |
| Targets | Technologies/platforms | Engineered biomaterials and cells | Merits and outcomes | References |
| templated (SMART) neurospheres | | | | |
| | designer injectable gels | shear-thinning hydrogel for injectable encapsulation and long-term delivery (SHIELD) hydrogels made from C7 protein, 8-arm PEG polymer modified with proline-rich peptides, and PNIPAAm for Schwann cell transplants | increased Schwann cell survival and retention, significantly improved spatial distribution within endogenous tissue, reduced cystic cavitation and neuronal loss, and substantially increased forelimb strength and coordination | (Marquardt et al., 2020) |
| | glycomaterial implants | acellular-engineered chondroitin sulfate (eCS) matrix with brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF-2) | accelerated cellular repair and gross motor function recovery, enhanced volumetric vascularization, activity-regulated cytoskeleton (Arc) protein expression, and perilesional sensorimotor connectivity in chronic severe TBI | (Latchoumane et al., 2021) |
| | Wharton's Jelly | scaffolds derived from human platelet lysate and human plasma fibrinogen with thrombin as a crosslinker and encapsulated with human mesenchymal stem cells (hMSCs) | demonstrated high survivability, stable proliferation rate, migration out of the hydrogel, upregulated expression of neurotrophic factors, cytokines, and neural markers, and increased expression of neural differentiation markers | (Lech et al., 2020) |
| | Elastic ECM | thin polyacrylamide substrates (PA), ECM with myelinating glia | demonstrated inhibited branching and differentiation of oligodendrocytes (OLs) on rigid, lesion-like matrices whereas Schwann cells (SCs) developed normally in both soft and stiffer matrices to promote healing and regeneration in both CNS and PNS | (Urbanski et al., 2016) |
| | HYDROSAP hydrogels | self-assembling peptides (SAPs) hydrogels with human neural stem cell (hNSC) | decreased astrogliosis and immune response, increased neuronal markers, improved hNSC engraftment, enhanced behavioral recovery, and formation of 3D functional neuronal networks | (Marchini et al., 2019) |
| | brain stiffness-mimicking gel | tilapia collagen gel with hiPSCs-derived dorsal cortical neurons | demonstrated lineage commitment to the terminal neural subtype, improved neurogenesis and neural function, and enhanced production of dorsal cortical neurons | (Iwashita et al., 2019) |
| | thermosensitive hydrogels combined growth factors | acellular spinal cord scaffold with bFGF and heparin-poloxamer (HP) for endogenous regeneration | efficient inhibition of glial scars and improved functional recovery via regeneration of nerve axons and the differentiation of neural stem cells in the SCI | (Xu et al., 2016) |
| | photoresponsive neuroprotective protein hydrogel | His6-tagged recombinant protein, SpyTag-ELP-CarHC-ELP-SpyTag (ACA), metal ions, and adenosylco-balamin with hMSCs and leukemia inhibitory factors (LIFs) | showed excellent injectability, photodegradability, facile encapsulation and delivery of cells and proteins, prolonged cellular signaling, and enhanced axon regeneration | (Jiang et al., 2020) |
| | multichannel polymer scaffold | PLGA scaffolds with activated Schwann cells and MSCs | exhibited significant recovery of nerve function, enhanced differentiation into neuron-like cells, good colocalization with host neurons, and formation of robust bundles of regenerated fibers | (Yang et al., 2017) |
| | bioactive scaffolds with enhanced supramolecular motion | library of IKVAV peptide amphiphiles with different sequences of amino acids $\mathrm{V}, \mathrm{A}$, and G (IKVAV PA1 to PA8) for endogenous regeneration | intensified molecular motions within scaffold fibrils enhanced vascular growth, axonal regeneration, myelination, survival of motor neurons, and functional recovery with reduced gliosis | (Álvarez et al., 2021) |
| | growth facilitators | diblock copolypeptide hydrogel K180L20 with FGF-2, EGF, GNDF for endogenous regeneration | regrew full spinal segment beyond lesion centers into neural tissue with terminal-like contacts and displaying synaptic markers, improved electrophysiological conduction, and reinstated developmentally essential mechanisms to facilitate axon growth | (Anderson et al., 2018) |
Targets Technologies/platforms Engineered biomaterials and cells Merits and outcomes References
3D scalable culture system PNIPAAm-PEG hydrogel with pluripotent stem cells from human oligodendrocyte precursors generated oligodendrocyte precursor cells (OPCs) in 3D culture without enrichment that displayed excellent engraftment, migration, and maturation into myelinating oligodendrocytes in vivo (Rodrigues et al., 2017)
Ocular system 3D micro and ultra-fine matrix porcine urinary bladder matrix (UBM) with a complex mixture of intracellular and extracellular proteins UBM particulate substantially reduced corneal haze and promoted proregenerative environments by stimulating type 2 immune response that led to improved wound healing and vision restoration (Wang et al., 2021a)
retinal cell sheets hESC-derived retinal pigment epithelial (RPE) cells sheets on human amniotic membrane rescued photoreceptor cells and improved visual acuity in models of retinal degeneration (M'Barek et al., 2017)
biosynthetic cornea recombinant human collagen type III (RHCIII) successful integration of the biosynthetic cornea that remained avascular without the use of long-term immunosuppression, restoration of the tear film, regeneration of nerves, and improvement in vision (Fagerholm et al., 2010)
polarized RPE polymer matrix adult human RPE stem cells on polyethylene terephthalate (PET) human RPE monolayer remained polarized and survived on PET carriers in the subretinal space (Stanzel et al., 2014)
rotating-wall vessel bioreactors retinal organoids derived from iPSC, ESCs cultured on a poly(2-hydroxyethyl methacrylate) (polyHEMA)-coated substrate improved bioprocess for organoid growth and differentiation in the rotating-wall vessel (RWV) bioreactors was observed (DiStefano et al., 2018)
ultrathin micromolded 3D scaffolds poly(glycerol sebacate) scaffold with retinal organoids generated from hPSCs microfabricated scaffolds patterned with high-density photoreceptors produced a multicellular photoreceptor layer for outer retinal reconstruction (Lee et al., 2021)
retinal pigment epithelium patch PLGA scaffolds with iPSC-derived RPE improved integration and functionality of RPE; promising alternative autologous therapy for dry and wet AMD (Sharma et al., 2019a)
self-organizing human retinal tissue hESC differentiation to neural retina (NR), GSK3, and FGFR inhibitors NR-RPE boundary tissue self-organizes a niche for ciliary margin stem cells and expands NR peripherally via de novo progenitor generation (Kuwahara et al., 2015)
substrate with matching corneal biomechanics type-I collagen substrates with limbal epithelial stem cell (LESC) Collagenase-treated burned surface of the cornea restores its appropriate mechanical properties and supports growth of undifferentiated LESCs by YAP suppression (Gouveia et al., 2019)
rhodopsin genomic loci DNA nanoparticles polyethylene glycol-substituted polylysine (CK30PEG) conjugated with TAT peptide, rhodopsin genomic loci DNA gDNA vectors resulted in long-term increased levels of transgene expression and helped rescue retinal degeneration (Zheng et al., 2020b)
bioprinted construct "gelatin methacryloyl with conjunctival stem cells
(CjSCs)" demonstrated injectable delivery of CjSC microtissue to treat of ocular surface diseases (Zhong et al., 2021)
Scaffold for thick sheet of retinal cells Scaffold composed of gelatin type A, chondroitin sulfate, and hyaluronic acid with hESCs successfully simulated the extracellular matrix of the neurosensory retina and supported differentiation into retinal cell types (Singh et al., 2018)
dual synthetic corneal tissue synthetic Bowman's membrane (sBM) and synthetic stromal layer (sSL) for endogenous repair supported rapid re-epithelialization, maintained corneal transparency, improved mechanical strength, and enabled host/ implant integration (Wang et al., 2020)
full-thickness artificial cornea acellular porcine cornea matrix (APCM) with limbal epithelial cell-like (LEC-like) cells and corneal endothelial cell-like (CEC-like) cells successful construction of a full-thickness cornea substitute with good host integration and transparency (Zhang et al., 2017)| Targets | Technologies/platforms | Engineered biomaterials and cells | Merits and outcomes | References |
| :---: | :---: | :---: | :---: | :---: |
| | 3D scalable culture system | PNIPAAm-PEG hydrogel with pluripotent stem cells from human oligodendrocyte precursors | generated oligodendrocyte precursor cells (OPCs) in 3D culture without enrichment that displayed excellent engraftment, migration, and maturation into myelinating oligodendrocytes in vivo | (Rodrigues et al., 2017) |
| Ocular system | 3D micro and ultra-fine matrix | porcine urinary bladder matrix (UBM) with a complex mixture of intracellular and extracellular proteins | UBM particulate substantially reduced corneal haze and promoted proregenerative environments by stimulating type 2 immune response that led to improved wound healing and vision restoration | (Wang et al., 2021a) |
| | retinal cell sheets | hESC-derived retinal pigment epithelial (RPE) cells sheets on human amniotic membrane | rescued photoreceptor cells and improved visual acuity in models of retinal degeneration | (M'Barek et al., 2017) |
| | biosynthetic cornea | recombinant human collagen type III (RHCIII) | successful integration of the biosynthetic cornea that remained avascular without the use of long-term immunosuppression, restoration of the tear film, regeneration of nerves, and improvement in vision | (Fagerholm et al., 2010) |
| | polarized RPE polymer matrix | adult human RPE stem cells on polyethylene terephthalate (PET) | human RPE monolayer remained polarized and survived on PET carriers in the subretinal space | (Stanzel et al., 2014) |
| | rotating-wall vessel bioreactors | retinal organoids derived from iPSC, ESCs cultured on a poly(2-hydroxyethyl methacrylate) (polyHEMA)-coated substrate | improved bioprocess for organoid growth and differentiation in the rotating-wall vessel (RWV) bioreactors was observed | (DiStefano et al., 2018) |
| | ultrathin micromolded 3D scaffolds | poly(glycerol sebacate) scaffold with retinal organoids generated from hPSCs | microfabricated scaffolds patterned with high-density photoreceptors produced a multicellular photoreceptor layer for outer retinal reconstruction | (Lee et al., 2021) |
| | retinal pigment epithelium patch | PLGA scaffolds with iPSC-derived RPE | improved integration and functionality of RPE; promising alternative autologous therapy for dry and wet AMD | (Sharma et al., 2019a) |
| | self-organizing human retinal tissue | hESC differentiation to neural retina (NR), GSK3, and FGFR inhibitors | NR-RPE boundary tissue self-organizes a niche for ciliary margin stem cells and expands NR peripherally via de novo progenitor generation | (Kuwahara et al., 2015) |
| | substrate with matching corneal biomechanics | type-I collagen substrates with limbal epithelial stem cell (LESC) | Collagenase-treated burned surface of the cornea restores its appropriate mechanical properties and supports growth of undifferentiated LESCs by YAP suppression | (Gouveia et al., 2019) |
| | rhodopsin genomic loci DNA nanoparticles | polyethylene glycol-substituted polylysine (CK30PEG) conjugated with TAT peptide, rhodopsin genomic loci DNA | gDNA vectors resulted in long-term increased levels of transgene expression and helped rescue retinal degeneration | (Zheng et al., 2020b) |
| | bioprinted construct | gelatin methacryloyl with conjunctival stem cells <br> (CjSCs) | demonstrated injectable delivery of CjSC microtissue to treat of ocular surface diseases | (Zhong et al., 2021) |
| | Scaffold for thick sheet of retinal cells | Scaffold composed of gelatin type A, chondroitin sulfate, and hyaluronic acid with hESCs | successfully simulated the extracellular matrix of the neurosensory retina and supported differentiation into retinal cell types | (Singh et al., 2018) |
| | dual synthetic corneal tissue | synthetic Bowman's membrane (sBM) and synthetic stromal layer (sSL) for endogenous repair | supported rapid re-epithelialization, maintained corneal transparency, improved mechanical strength, and enabled host/ implant integration | (Wang et al., 2020) |
| | full-thickness artificial cornea | acellular porcine cornea matrix (APCM) with limbal epithelial cell-like (LEC-like) cells and corneal endothelial cell-like (CEC-like) cells | successful construction of a full-thickness cornea substitute with good host integration and transparency | (Zhang et al., 2017) |
nuew 10 łd!ısnuew ıoyłn https://cdn.mathpix.com/cropped/2024_11_10_3ad04f7655f7ffbe4d46g-54.jpg?height=724&width=56&top_left_y=364&top_left_x=62
Targets Technologies/platforms Engineered biomaterials and cells Merits and outcomes References
pancreatic tissues organoid microphysiological system machined fluidic chips from optically clear PMMA and PFA membrane with islets isolated from rodents demonstrated dynamic in vitro microenvironment for the preservation of primary organoid function (Patel et al., 2021)
electrogenetic macroencapsulation device bioelectronic encapsulation device with electrosensitive designer cells (Electroß cells) demonstrated wireless electrical stimulation of vesicular insulin release to attenuate postprandial hyperglycemia (Krawczyk et al., 2021),
rapid oxygenation of cell encapsulation SONIC scaffold poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) with islets isolated from rodents biomimetic scaffold with internal continuous air channels enhanced O_(2) diffusivity by 10,000 -fold and thus survival of transplanted graft (Wang et al., 2021b)
convection-enhanced macroencapsulation device (ceMED) poly(methyl methacrylate) (PMMA), PTFE membranes, and HF modified polyethersulfone with stem cell-derived beta-cells 3D geometry of ceMED maximized cell loading, improved GSIS and nutrient exchange due to convection, enhanced cell viability, and rapid reduction of hyperglycemia (Yang et al., 2021)
fluorocapsules 19F MRI detectable perfluoro-15-crown-5-ether (PFC) and Ba^(2+)-gelled alginate microcapsules with luciferase-expressing mouse beta TC6 insulinoma cells demonstrated the use of 19F MRI signal as a predictive imaging surrogate biomarker for monitoring failure of encapsulated islet cell therapy (Arifin et al., 2019)
cell-particle hybrids polymeric microspheres PLGA and FK506 (Tacrolimus) immune suppressant with islets isolated from rodents demonstrated a method for local immunomodulation with higher efficacy and safety; the platform can be applied for cell tracking and combinatorial deliveries of therapeutic entities (Nguyen et al., 2019)
exosome loaded immunomodulatory biomaterials (AlgXO) UPLVG alginate and exosomes with umbilical cord-derived mesenchymal stem cells (UC-MSCs) and rodent islets successfully attenuated the local immune microenvironment by suppressing proinflammatory macrophages partly by interfering with NF-kB pathway (Mohammadi et al., 2021)
amino acid augmented macro-encapsulation device polycaprolactone, alanine, and glutamine with stem cell-derived beta-cells enhanced viability of encapsulated beta-cells in nutrient-limited conditions (Chendke et al., 2019)
ready-to-use cryopreserved pancreatic islets trehalose, MitoQ, and DMSO with rodent islets demonstrated an improved cryopreservation method to increase the on-demand availability of islets for transplantation (Dolezalova et al., 2021)
graphene-Dex bioscaffolds graphene, nickel foam, and PMMA with ADMSCs and rodent islets graphene bioscaffold functionalized for local immunomodulation by Dex together with AD-MSC significantly improved the survival and function of transplanted islets (Razavi et al., 2021)
zwitterionic polyurethane (ZPU) nanoporous device 3-(Butylbis(2-hydroxyethyl) ammonio) propane-1sulfonate (SB-Diol) and Polyurethanes with rodent islets electrospun ZPU device lowered FBR when implanted in immunocompetent animals and showed better scalability and retrievability (Liu et al., 2021)
lotus-root-shaped cellencapsulated constructs (LENCON) microfluidic multicoaxial encapsulation device, laminin, and sodium hyaluronate with human stem cell-derived pancreatic beta-cells (hSC- betas ) demonstrated scalability, retrievability, and maintained the functionality of beta-cells in immunocompetent animals (Ozawa et al., 2021)
cellulose-based scaffolds carboxymethyl cellulose (CMC) cryogels with INS1E beta-cells prompted beta-cells to generate clusters and create specific ranges of pseudoislets; these scaffolds can control the organization and function of insulin-producing beta-cells (Velasco-Mallorquí et al., 2021)
extracellular matrix/alginate hydrogels pancreatic acellular matrix and pECM// alginate hydrogel with iPSC-derived beta-cells provided an ideal biomimetic microenvironment, improved differentiation efficiency, promoted insulin secretion, and increased expression of insulin-related genes (Wang et al., 2021c)| nuew 10 | łd!ısnuew ıoyłn | | ![](https://cdn.mathpix.com/cropped/2024_11_10_3ad04f7655f7ffbe4d46g-54.jpg?height=724&width=56&top_left_y=364&top_left_x=62) | |
| :---: | :---: | :---: | :---: | :---: |
| Targets | Technologies/platforms | Engineered biomaterials and cells | Merits and outcomes | References |
| pancreatic tissues | organoid microphysiological system | machined fluidic chips from optically clear PMMA and PFA membrane with islets isolated from rodents | demonstrated dynamic in vitro microenvironment for the preservation of primary organoid function | (Patel et al., 2021) |
| | electrogenetic macroencapsulation device | bioelectronic encapsulation device with electrosensitive designer cells (Electroß cells) | demonstrated wireless electrical stimulation of vesicular insulin release to attenuate postprandial hyperglycemia | (Krawczyk et al., 2021), |
| | rapid oxygenation of cell encapsulation SONIC scaffold | poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) with islets isolated from rodents | biomimetic scaffold with internal continuous air channels enhanced $\mathrm{O}_{2}$ diffusivity by 10,000 -fold and thus survival of transplanted graft | (Wang et al., 2021b) |
| | convection-enhanced macroencapsulation device (ceMED) | poly(methyl methacrylate) (PMMA), PTFE membranes, and HF modified polyethersulfone with stem cell-derived beta-cells | 3D geometry of ceMED maximized cell loading, improved GSIS and nutrient exchange due to convection, enhanced cell viability, and rapid reduction of hyperglycemia | (Yang et al., 2021) |
| | fluorocapsules | 19F MRI detectable perfluoro-15-crown-5-ether (PFC) and $\mathrm{Ba}^{2+}$-gelled alginate microcapsules with luciferase-expressing mouse $\beta$ TC6 insulinoma cells | demonstrated the use of 19F MRI signal as a predictive imaging surrogate biomarker for monitoring failure of encapsulated islet cell therapy | (Arifin et al., 2019) |
| | cell-particle hybrids polymeric microspheres | PLGA and FK506 (Tacrolimus) immune suppressant with islets isolated from rodents | demonstrated a method for local immunomodulation with higher efficacy and safety; the platform can be applied for cell tracking and combinatorial deliveries of therapeutic entities | (Nguyen et al., 2019) |
| | exosome loaded immunomodulatory biomaterials (AlgXO) | UPLVG alginate and exosomes with umbilical cord-derived mesenchymal stem cells (UC-MSCs) and rodent islets | successfully attenuated the local immune microenvironment by suppressing proinflammatory macrophages partly by interfering with NF-kB pathway | (Mohammadi et al., 2021) |
| | amino acid augmented macro-encapsulation device | polycaprolactone, alanine, and glutamine with stem cell-derived beta-cells | enhanced viability of encapsulated beta-cells in nutrient-limited conditions | (Chendke et al., 2019) |
| | ready-to-use cryopreserved pancreatic islets | trehalose, MitoQ, and DMSO with rodent islets | demonstrated an improved cryopreservation method to increase the on-demand availability of islets for transplantation | (Dolezalova et al., 2021) |
| | graphene-Dex bioscaffolds | graphene, nickel foam, and PMMA with ADMSCs and rodent islets | graphene bioscaffold functionalized for local immunomodulation by Dex together with AD-MSC significantly improved the survival and function of transplanted islets | (Razavi et al., 2021) |
| | zwitterionic polyurethane (ZPU) nanoporous device | 3-(Butylbis(2-hydroxyethyl) ammonio) propane-1sulfonate (SB-Diol) and Polyurethanes with rodent islets | electrospun ZPU device lowered FBR when implanted in immunocompetent animals and showed better scalability and retrievability | (Liu et al., 2021) |
| | lotus-root-shaped cellencapsulated constructs (LENCON) | microfluidic multicoaxial encapsulation device, laminin, and sodium hyaluronate with human stem cell-derived pancreatic beta-cells (hSC- $\beta \mathrm{s}$ ) | demonstrated scalability, retrievability, and maintained the functionality of beta-cells in immunocompetent animals | (Ozawa et al., 2021) |
| | cellulose-based scaffolds | carboxymethyl cellulose (CMC) cryogels with INS1E beta-cells | prompted beta-cells to generate clusters and create specific ranges of pseudoislets; these scaffolds can control the organization and function of insulin-producing beta-cells | (Velasco-Mallorquí et al., 2021) |
| | extracellular matrix/alginate hydrogels | pancreatic acellular matrix and $\mathrm{pECM} /$ alginate hydrogel with iPSC-derived beta-cells | provided an ideal biomimetic microenvironment, improved differentiation efficiency, promoted insulin secretion, and increased expression of insulin-related genes | (Wang et al., 2021c) |