4 research outputs found
The Regenerative Capacity of Tissue-Engineered Amniotic Membranes
Scaffolds can be
introduced as a source of tissue in
reconstructive
surgery and can help to improve wound healing. Amniotic membranes
(AMs) as scaffolds for tissue engineering have emerged as promising
biomaterials for surgical reconstruction due to their regenerative
capacity, biocompatibility, gradual degradability, and availability.
They also promote fetal-like scarless healing and provide a bioactive
matrix that stimulates cell adhesion, migration, and proliferation.
The aim of this study was to create a tissue-engineered AM-based implant
for the repair of vesicovaginal fistula (VVF), a defect between the
bladder and vagina caused by prolonged obstructed labor. Layers of
AMs (with or without cross-linking) and electrospun poly-4-hydroxybutyrate
(P4HB) (a synthetic, degradable polymer) scaffold were joined together
by fibrin glue to produce a multilayer scaffold. Human vaginal fibroblasts
were seeded on the different constructs and cultured for 28 days.
Cell proliferation, cell morphology, collagen deposition, and metabolism
measured by matrix metalloproteinase (MMP) activity were evaluated.
Vaginal fibroblasts proliferated and were metabolically active on
the different constructs, producing a distributed layer of collagen
and proMMP-2. Cell proliferation and the amount of produced collagen
were similar across different groups, indicating that the different
AM-based constructs support vaginal fibroblast function. Cell morphology
and collagen images showed slightly better alignment and organization
on the un-cross-linked constructs compared to the cross-linked constructs.
It was concluded that the regenerative capacity of AM does not seem
to be affected by mechanical reinforcement with cross-linking or the
addition of P4HB and fibrin glue. An AM-based implant for surgical
repair of internal organs requiring load-bearing functionality can
be directly translated to other types of surgical reconstruction of
internal organs
High heparin content surface-modified polyurethane discs promote rapid and stable angiogenesis in full thickness skin defects through VEGF immobilization
Three-dimensional scaffolds have the capacity to serve as an architectural framework to guide and promote tissue regeneration. Parameters such as the type of material, growth factors, and pore dimensions are therefore critical in the scaffold's success. In this study, heparin has been covalently bound to the surface of macroporous polyurethane (PU) discs via two different loading methods to determine if the amount of heparin content had an influence on the therapeutic affinity loading and release of (VEGF165 ) in full thickness skin defects. PU discs (5.4 mm diameter, 300 µm thickness, and interconnected pore size of 150 µm) were produced with either a low (2.5 mg/g) or high (6.6 mg/g) heparin content (LC and HC respectively), and were implanted into the modified dorsal skin chamber (MDSC) of C57BL/6 J mice with and without VEGF. Both low- and high-content discs with immobilized VEGF165 (LCV and HCV, respectively) presented accelerated neovascularization and tissue repair in comparison to heparin discs alone. However, the highest angiogenetic peak was on day 7 with subsequent stabilization for HCV, whereas other groups displayed a delayed peak on day 14. We therefore attribute the superior performance of HCV due to its ability to hold more VEGF165, based on its increased heparin surface coverage, as also demonstrated in VEGF elution dynamics. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2543-2550, 2017
Covalent surface heparinization potentiates porous polyurethane scaffold vascularization
Porous scaffolds play an integral role in many tissue-engineering approaches, and the ability to improve vascularization, without eliciting an excessive inflammatory response, would constitute an important step towards achieving long-term healing and function of devices made from these materials. After having previously optimized the dimensional requirements of the well-defined pores, the present study aimed at a further shift from inflammation to vascularization via surface immobilization with heparin. Porous polyurethane disks were produced to contain well-defined pores (147 +/- 2 microm) with abundant interconnecting windows (67 +/- 2 microm). After heparinization via copolymer grafting and amination to contain 32 microg of heparin, the modification appeared as a uniform layer on all exposed surfaces, with no signs of pore obliteration or significant changes in pore size. After 28 days implantation in a rat subcutaneous model, the scaffolds were assessed for vascularization/arteriolization and inflammation using CD31/actin and ED-1 staining, respectively. Heparinization resulted in a significant increase in vascularization: capillaries increased by 62% in number (66.2 +/- 0.8 to 107.3 +/- 1.4 vessels/mm(2); p<0.03) and 56% in total area (0.9 +/- 0.1 to 1.4 +/- 0.02%; p<0.02). Arteriolization also increased in absolute terms (200% in number; p<0.03), but did not change significantly when normalized to capillary number. Heparinization did not significantly affect the inflammatory response at this time-point, as quantified by ED-1 positive macrophage and foreign body giant cell (FBGC) content. Thus, the in vivo vascularization of porous scaffolds could be increased without concomitant increase in the inflammatory response by employing a simple surface modification technique. This could be a valuable tool for in vivo tissue engineering applications where enhanced vascularization is required