The Efficacy of a Prevascularized, Retrievable Poly(D,L,-lactide-co-ε-caprolactone) Subcutaneous Scaffold as Transplantation Site for Pancreatic Islets

Smink, Alexandra M.; Li, Shiri; Hertsig, Don T.; Haan, Bart J. de; Schwab, Leendert W.; Apeldoorn, Aart van; Koning, Eelco J.P. de; Faas, Marijke M.; Lakey, Jonathan R.T.; Vos, Paul de

doi:10.1097/tp.0000000000001663

Cited by 52 publications

(58 citation statements)

References 43 publications

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“…38 This is supported by clinical studies demonstrating even detrimental effects after injections of a single growth factor. [39][40][41] Liposome injections may also have a negative effect on graft outcome in our study, since in our previous study, 42 transplantation of 800 islets into the preimplanted PDLLCL scaffold (in the absence of liposomes) induced normoglycemia in 80% of the recipients. This was only 40% in the current study where controls received empty liposomes.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia

Smink

Swart

et al. 2017

J Biomedical Materials Res

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The liver as transplantation site for pancreatic islets is associated with significant loss of islets, which can be prevented by grafting in a prevascularized, subcutaneous scaffold. Supporting vascularization of a scaffold to limit the period of ischemia is challenging and was developed here by applying liposomes for controlled release of angiogenic factors. The angiogenic capacity of platelet‐derived growth factor, vascular endothelial growth factor, acidic fibroblast growth factor (aFGF), and basic FGF were compared in a tube formation assay. Furthermore, the release kinetics of different liposome compositions were tested. aFGF and L‐α‐phosphatidylcholine/cholesterol liposomes were selected to support vascularization. Two dosages of aFGF‐liposomes (0.5 and 1.0 μg aFGF per injection) were administered weekly for a month after which islets were transplanted. We observed enhanced efficacy in the immediate post‐transplant period compared to the untreated scaffolds. However, on the long‐term, glucose levels of the aFGF treated animals started to increase to diabetic levels. These results suggest that injections with aFGF liposomes do improve vascularization and the immediate restoration of blood glucose levels but does not facilitate the long‐term survival of islets. Our data emphasize the need for long‐term studies to evaluate potential beneficial and adverse effects of vascularization protocols of scaffolds. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2533–2542, 2017.

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Section: Discussionmentioning

confidence: 99%

Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia

Smink

Swart

et al. 2017

J Biomedical Materials Res

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“…Alternatively, devices based on polymeric porous scaffolds are found to be simple in terms of surgical manipulation, offer an adequate volume for islet loading, provide mechanical graft protection and may be easily retrievable in the case of graft infection. 16,17 In our study we have focused on the creation of a pre-vascularized pouch with an adequate inner volume, without considerable inflammation in the time of transplantation and rich in a vascular/capillary network on the internal surface. We believe that such induced pre-vascularization could significantly shorten the "hypoxia" time when islets are dependent on oxygen diffusion.…”

Section: Introductionmentioning

confidence: 99%

Bioengineering a pre-vascularized pouch for subsequent islet transplantation using VEGF-loaded polylactide capsules

et al. 2020

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“…It is therefore necessary to ensure the availability of oxygen and nutrients as delivered by a perfused vasculature. For such vascularization purposes, porous three-dimensional biomaterials have been used as subcutaneous medical devices in the field of tissue engineering 22,23,26,38 . The pore structure of these biomaterials allows blood vessel infiltration and thereby reduction of diffusional distances and barriers between the neovasculature and the cells.…”

Section: Discussionmentioning

confidence: 99%

Non-Invasive Monitoring of Oxygen Tension and Oxygen Transport Inside Subcutaneous Devices After H₂S Treatment

et al. 2020

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Medical devices for cell therapy can be improved through prevascularization. In this work we study the vascularization of a porous polymer device, previously used by our group for pancreatic islet transplantation with results indicating improved glycemic control. Oxygen partial pressure within such devices was monitored non-invasively using an optical technique. Oxygen-sensitive tubes were fabricated and placed inside devices prior to subcutaneous implantation in nude mice. We tested the hypothesis that vascularization will be enhanced by administration of the pro-angiogenic factor hydrogen sulfide (H2S). We found that oxygen dynamics were unique to each implant and that the administration of H2S does not result in significant changes in perfusion of the devices as compared with control. These observations suggest that vascular perfusion and density are not necessarily correlated, and that the rate of vascularization was not enhanced by the pro-angiogenic agent.

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The Efficacy of a Prevascularized, Retrievable Poly(D,L,-lactide-co-ε-caprolactone) Subcutaneous Scaffold as Transplantation Site for Pancreatic Islets

Abstract: Our findings demonstrate that the prevascularized poly (D,L-lactide-co-ε-caprolactone) scaffold maintains viability and function of islets in the subcutaneous site.

Cited by 52 publications

References 43 publications

Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia

Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia

Bioengineering a pre-vascularized pouch for subsequent islet transplantation using VEGF-loaded polylactide capsules

Non-Invasive Monitoring of Oxygen Tension and Oxygen Transport Inside Subcutaneous Devices After H₂S Treatment

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The Efficacy of a Prevascularized, Retrievable Poly(D,L,-lactide-co-ε-caprolactone) Subcutaneous Scaffold as Transplantation Site for Pancreatic Islets

Abstract: Our findings demonstrate that the prevascularized poly (D,L-lactide-co-ε-caprolactone) scaffold maintains viability and function of islets in the subcutaneous site.

Cited by 52 publications

References 43 publications

Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia

Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia

Bioengineering a pre-vascularized pouch for subsequent islet transplantation using VEGF-loaded polylactide capsules

Non-Invasive Monitoring of Oxygen Tension and Oxygen Transport Inside Subcutaneous Devices After H2S Treatment

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Non-Invasive Monitoring of Oxygen Tension and Oxygen Transport Inside Subcutaneous Devices After H₂S Treatment