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International Journal of Bioprinting                                   Biofabrication for islet transplantation




            PLGA-porous  microspheres  upregulated the  expression   strategy for encapsulating transplanted islets using a
            of vascular-related genes, indicating their potential   conformal coating (CC) technique with PEG hydrogels .
                                                                                                           [67]
            to  promote vascular  formation  during  artificial organ   This method produces hydrogel CCs that encompass
            construction using PLGA-porous microspheres .      the islets at physiological pH, thereby promoting
                                                  [58]
               Polylactic acid (PLA) is an aliphatic polyester that   cytocompatibility and scalability. To evaluate the efficacy
            degrades  through  hydrolysis.  It  exhibits  desirable   and efficiency of this novel method, in vitro and in vivo
            characteristics such  as biocompatibility, degradability,   experiments were conducted using various small and large
            and printability, making it a popular choice for use as a   animal models of T1D (Figure 3E). During the evaluation
            polymeric bioink . The  incorporation of  PLA allows   of dynamic glucose-stimulated insulin secretion, both
                          [59]
            for the facile production of porous scaffolds that can   naked and emulsion-coated human islets exhibited a
            effectively promote the growth of neotissues. To date, a   characteristic perifusion profile characterized by an initial
            diverse array of medical products has been developed   phase of insulin secretion reaching its peak, followed by
            utilizing PLA, including degradable constructs and   a  subsequent  phase  wherein  insulin  secretion plateaued
                                                        [60]
            porous scaffolds for tissue engineering applications .   during the high-glucose stimulus (Figure 3F). The results
            Huang  et  al. presented an innovative co-transplantation   revealed improved biocompatibility and abundant graft
                                                                                       [67]
            system that employed nanocomposite microgels loaded   revascularization (Figure 3G) . Another distinguishing
            with islets and was capable of a sustained in situ release of   feature of PEG is its potential to be modified with specific
            immunosuppressants in conjunction with biodegradable   ligands to promote tissue adhesion. This property permits
            oxygen-generating microspheres (Figure 3C) . In their   targeted cell attachment and proliferation, which is highly
                                                 [61]
            study,  PLA  was  selected  as  the  microsphere  packaging   advantageous in tissue engineering applications, where
            material because of its biodegradability. Co-transplantation   successful regeneration hinges on cell adhesion. Despite
            of  nanocomposite  microgels  and  biodegradable   their usefulness, the biocompatibility of hydrophobic
            microspheres into diabetic mice restored and maintained   materials is restricted by their inherent nature, and the
            normoglycemia  (Figure  3D) .  Hoveizi  and  Tavakol   breakdown of these materials can release acidic byproducts
                                    [61]
                                                                                        [68]
            successfully engineered a dependable 3D differentiation   with proinflammatory effects . Furthermore, several
            methodology for mesenchymal stem cells (MSCs) into   synthetic materials employed in tissue engineering,
            pancreatic beta cell precursors (PBCPs) using nanofibrous   including PEG, are non-biodegradable and may remain
            PLA  scaffolds .  The  biocompatible  and  biodegradable   indefinitely in the body, possibly causing unfavorable
                       [62]
            nature of the nanofibrous PLA scaffold provided a suitable   reactions or necessitating surgical removal.
            biophysical microenvironment for MSCs. Remarkably,   3.4. Decellularized tissue-driven ECM
            transplanted PBCPs have demonstrated the ability to   Tissue decellularization refers to the removal of cellular
            ameliorate  hyperglycemia  in  a  murine  diabetes-induced   components from a tissue or solid organ, resulting
            model . However, the degradation of PLA generates   in an acellular 3D structure composed of the ECM.
                 [62]
            acidic byproducts, which negatively impact its long-term   Decellularized extracellular matrix (dECM) exhibits
            biocompatibility by triggering tissue inflammation and   non-toxicity toward the proliferation and differentiation
            cellular death.                                    of various cell types, indicating its potential utility in
               Polyethylene glycol (PEG) has emerged as a promising   regenerative medicine. Recent research on tissue-specific
            material for islet encapsulation owing to its tunable   dECM has effectively provided a vital microenvironment
            properties and gelation ability, which facilitate crosslinking   for  cells,  allowing  for  the  modulation  of  cellular
            and photopolymerization [63,64] . Several studies have   processes such as migration, differentiation, and function
            demonstrated the ability of PEG to encapsulate thinner   during tissue morphogenesis [69,70] . The pancreatic
            islets.  For  instance,  a  thin  layer-by-layer  PEG  approach   dECM, comprising collagen, laminin, fibronectin, and
            was utilized in one study to create an ultrathin capsule   fibrin, plays a crucial role in cytoskeletal remodeling,
            for surrounding the islets, which significantly enhanced   contractility, and cell differentiation. The dECM of
            the molecular exchange across the membrane compared   the pancreas offers significant advantages, such as
            with earlier methods . Weaver  et al. incorporated   biocompatibility and bioactivity, which can increase islet
                              [65]
            PEG hydrogel into a macroencapsulation device for   survival and decrease cytotoxicity, thereby enhancing
            extrahepatic islet transplantation . The device comprises   islet function. Research focusing on dECM derived
                                      [66]
            a hydrogel core crosslinked with non-degradable PEG   from pancreatic tissue  has  validated  its characteristics,
            dithiol and an outer layer that is vasculogenic and   especially regarding the interactions between islets and
            crosslinked with  a proteolytically  sensitive  peptide  to   environmental cues, including viability, insulin secretion,
            stimulate degradation . Stock et al. introduced a refined   and glucose responsiveness (Table 1) .
                                                                                             [71]
                             [66]
            Volume 9 Issue 6 (2023)                        399                        https://doi.org/10.36922/ijb.1024
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