Degradation, intra-articular retention and biocompatibility of monospheres composed of [PDLLA-PEG-PDLLA]-b-PLLA multi-block copolymers

Sandker, Maria J.; Duque, Luisa F.; Redout, Everaldo M.; Chan, Alan; Que, Ivo; Löwik, Clemens W.G.M.; Klijnstra, Evelien C.; Kops, Nicole; Steendam, Rob; Weeren, René van; Hennink, Wim E.; Weinans, Harrie

doi:10.1016/j.actbio.2016.11.003

Cited by 20 publications

(36 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We showed that we can consistently create uniform, cell-laden microspheres for in vivo injection, the equine ECFCs survive encapsulation and injection, and PEG-Fb MS encapsulated labeled ECFCs were detected in tissues up to 3 weeks after injection. The PEG-Fb material was observed only up to 1 week after injection, and this is consistent with the ease of hydrogel breakdown in vivo [22,23]. The fibrinogen backbone of the PEG-Fb biomaterial provides cell adhesion / integrin binding sites found naturally in extracellular matrix proteins, which may have aided cell retention at the point of injection [23,26].…”

Section: Discussionsupporting

confidence: 65%

“…This is also the first study evaluating a cellular therapy for wound healing that utilizes PEG-Fb microspheres, a biomaterial cell-delivery vehicle designed in an injectable format. Biomaterial support of cells during delivery is very attractive in order to protect cells during or after injection and increase cell retention after injection [16,22,23]. Combining mesenchymal stem cells (MSCs) with an alginate scaffold biomaterial helped to successfully regenerate articular cartilage in a rabbit model [24].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cell engraftment, vascularization, and inflammation after treatment of equine distal limb wounds with endothelial colony forming cells encapsulated within hydrogel microspheres

et al. 2020

View full text Add to dashboard Cite

Background: Endothelial colony forming cells (ECFCs) may be useful therapeutically in conditions with poor blood supply, such as distal limb wounds in the horse. Encapsulation of ECFCs into injectable hydrogel microspheres may ensure cell survival and cell localization to improve neovascularization and healing. Autologous ECFCs were isolated from 6 horses, labeled with quantum nanodots (QD), and a subset were encapsulated in poly(ethylene) glycol fibrinogen microspheres (PEG-Fb MS). Full-thickness dermal wounds were created on each distal limb and injected with empty PEG-Fb MS, serum, ECFCs, or ECFCs encapsulated into PEG-Fb MS (ECFC/MS). Analysis included wound surface area (WSA), granulation tissue scoring (GS), thermography, collagen density staining, and immunohistochemical staining for endothelial and inflammatory cells. The purpose of this study was to track cell location and evaluate wound vascularization and inflammatory response after injection of ECFC/MS or naked ECFCs in equine distal limb wounds. Results: ECFCs were found near and within newly formed blood vessels up to 3 weeks after injection. ECFC and ECFC/MS groups had the greatest blood vessel quantity at week 1 in the wound periphery. Wounds treated with ECFCs and ECFC/MS had the lowest density of neutrophils and macrophages at week 4. There were no significant effects of ECFC or ECFC/MS treatment on other measured parameters. Conclusions: Injection of microsphere encapsulated ECFCs was practical for clinical use and well-tolerated. The positive ECFC treatment effects on blood vessel density and wound inflammation warrant further investigation.

show abstract

Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Cell engraftment, vascularization, and inflammation after treatment of equine distal limb wounds with endothelial colony forming cells encapsulated within hydrogel microspheres

et al. 2020

View full text Add to dashboard Cite

show abstract

“…40−42 The swelling degree of these [PCL–PEG–PCL]- b -[PLLA] polymers is dependent on the weight fraction and molecular weight of PEG. 42,43 We hypothesized that the release characteristics of VEGF from multiblock copolymeric microspheres can be tailored by blending multiblock copolymers with different swelling degrees.…”

Section: Introductionmentioning

confidence: 99%

Sustained Release of Vascular Endothelial Growth Factor from Poly(ε-caprolactone-PEG-ε-caprolactone)-b-Poly(l-lactide) Multiblock Copolymer Microspheres

Scheiner

Maas-Bakker

Nguyễn³

et al. 2019

ACS Omega

Self Cite

View full text Add to dashboard Cite

Vascular endothelial growth factor (VEGF) is the major regulating factor for the formation of new blood vessels, also known as angiogenesis. VEGF is often incorporated in synthetic scaffolds to promote vascularization and to enhance the survival of cells that have been seeded in these devices. Such applications require sustained local delivery of VEGF of around 4 weeks for stable blood vessel formation. Most delivery systems for VEGF only provide short-term release for a couple of days, followed by a release phase with very low VEGF release. We now have developed VEGF-loaded polymeric microspheres that provide sustained release of bioactive VEGF for 4 weeks. Blends of two swellable poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone)- b -poly( l -lactide) ([PCL–PEG–PCL]- b -[PLLA])-based multiblock copolymers with different PEG content and PEG molecular weight were used to prepare the microspheres. Loading of the microspheres was established by a solvent evaporation-based membrane emulsification method. The resulting VEGF-loaded microspheres had average sizes of 40–50 μm and a narrow size distribution. Optimized formulations of a 50:50 blend of the two multiblock copolymers had an average VEGF loading of 0.79 ± 0.09%, representing a high average VEGF loading efficiency of 78 ± 16%. These microspheres released VEGF continuously over 4 weeks in phosphate-buffered saline pH 7.4 at 37 °C. This release profile was preserved after repeated and long-term storage at −20 °C for up to 9 months, thereby demonstrating excellent storage stability. VEGF release was governed by diffusion through the water-filled polymer matrix, depending on PEG molecular weight and PEG content of the polymers. The bioactivity of the released VEGF was retained within the experimental error in the 4-week release window, as demonstrated using a human umbilical vein endothelial cells proliferation assay. Thus, the microspheres prepared in this study are suitable for embedment in polymeric scaffolds with the aim of promoting their functional vascularization.

show abstract

“…These multiblock copolymers form amorphous domains [primarily consisting of poly(ε-caprolactone)poly(ethylene glycol)-poly(ε-caprolactone) blocks] and semicrystalline domains [mainly composed of poly(L-lactic acid) blocks], and are attractive for protein delivery due to their wellcontrolled swelling properties which allow continuous release through diffusion with low burst release. [32][33][34][35] The release of proteins can be tailored by the weight fraction and molecular weight (M w ) of poly(ethylene glycol) (PEG), 33,36 which was also demonstrated for microspheres loaded with VEGF. 35 In this study, we incorporated VEGF-loaded microspheres in poly(dimethylsiloxane) (PDMS)-based devices 37 and studied the release of VEGF and its bioactivity.…”

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial Growth Factor–Releasing Microspheres Based on Poly(ε-Caprolactone-PEG-ε-Caprolactone)-b-Poly(L-Lactide) Multiblock Copolymers Incorporated in a Three-Dimensional Printed Poly(Dimethylsiloxane) Cell Macroencapsulation Device

Scheiner

Coulter

Maas-Bakker

et al. 2020

Journal of Pharmaceutical Sciences

Self Cite

View full text Add to dashboard Cite

Pancreatic islet transplantation is a promising advanced therapy that has been used to treat patients suffering from diabetes type 1. Traditionally, pancreatic islets are infused via the portal vein, which is subsequently intended to engraft in the liver. Severe immunosuppressive treatments are necessary, however, to prevent rejection of the transplanted islets. Novel approaches therefore have focused on encapsulation of the islets in biomaterial implants which can protect the islets and offer an organ-like environment. Vascularization of the device's surface is a prerequisite for the survival and proper functioning of transplanted pancreatic islets. We are pursuing a prevascularization strategy by incorporation of vascular endothelial growth factor (VEGF)-loaded microspheres in 3-dimensional printed poly(dimethylsiloxane)-based devices prior to their prospective loading with transplanted cells. Microspheres (~50 mm) were based on poly(ε-caprolactone-PEG-ε-caprolactone)-b-poly(L-lactide) multiblock copolymers and were loaded with 10 mg VEGF/mg microspheres, and subsequently dispersed in a hyaluronic acid carrier liquid. In vitro release studies at 37 C demonstrated continuous release of fully bioactive VEGF for 4 weeks. In conclusion, our results demonstrate that incorporation of VEGF-releasing microspheres ensures adequate release of VEGF for a time window of 4 weeks, which is attractive in view of the vascularization of artificial pancreas implants.

show abstract

Degradation, intra-articular retention and biocompatibility of monospheres composed of [PDLLA-PEG-PDLLA]-b-PLLA multi-block copolymers

Cited by 20 publications

References 82 publications

Cell engraftment, vascularization, and inflammation after treatment of equine distal limb wounds with endothelial colony forming cells encapsulated within hydrogel microspheres

Cell engraftment, vascularization, and inflammation after treatment of equine distal limb wounds with endothelial colony forming cells encapsulated within hydrogel microspheres

Sustained Release of Vascular Endothelial Growth Factor from Poly(ε-caprolactone-PEG-ε-caprolactone)-b-Poly(l-lactide) Multiblock Copolymer Microspheres

Vascular Endothelial Growth Factor–Releasing Microspheres Based on Poly(ε-Caprolactone-PEG-ε-Caprolactone)-b-Poly(L-Lactide) Multiblock Copolymers Incorporated in a Three-Dimensional Printed Poly(Dimethylsiloxane) Cell Macroencapsulation Device

Contact Info

Product

Resources

About