Effect of bFGF and fibroblasts combined with hyaluronic acid-based hydrogels on soft tissue augmentation: an experimental study in rats

Abstract

BackgroundHyaluronic acid (HA) has been applied as a primary biomaterial for temporary soft tissue augmentation and as a carrier for cells and the delivery of growth factors to promote tissue regeneration. Although HA derivatives are the most versatile soft tissue fillers on the market, they are resorbed early, within 3 to 12 months. To overcome their short duration, they can be combined with cells or growth factors. The purpose of this study was to investigate the stimulating effects of human fibroblasts and basic fibroblast growth factors (bFGF) on collagen synthesis during soft tissue augmentation by HA hydrogels and to compare these with the effects of a commercial HA derivative (Restylane®).MethodsThe hydrogel group included four conditions. The first condition consisted of hydrogel (H) alone as a negative control, and the other three conditions were bFGF-containing hydrogel (HB), human fibroblast-containing hydrogel (HF), and human fibroblast/bFGF-containing hydrogel (HBF). In the Restylane® group (HGF), the hydrogel was replaced with Restylane® (R, RB, RF, RBF). The gels were implanted subdermally into the back of each nude mouse at four separate sites. Twelve nude mice were used for the hydrogel (n = 6) and Restylane® groups (n = 6). The specimens were harvested 8 weeks after implantation and assessed histomorphometrically, and collagen synthesis was evaluated by RT-PCR.ResultsThe hydrogel group showed good biocompatibility with the surrounding tissues and stimulated the formation of a fibrous matrix. HBF and HF showed significantly higher soft tissue synthesis compared to H (p < 0.05), and human collagen type I was well expressed in HB, HF, and HBF; HBF showed the strongest expression. The Restylane® filler was surrounded by a fibrous capsule without any soft tissue infiltration from the neighboring tissue, and collagen synthesis within the Restylane® filler could not be observed, even though no inflammatory reactions were observed.ConclusionThis study revealed that HA-based hydrogel alone or hydrogel combined with fibroblasts and/or bFGF can be effectively used for soft tissue augmentation.

Cellular infiltration in an injectable sulfated cellulose nanocrystal hydrogel and efficient angiogenesis by VEGF loading

“…Also, subcutaneously implanted poly(N-isopropyl acrylamide) (PNIPAAm)-based biosensor showed ~ 30 μm of the fibrous capsule after 30 days [ 48 ]. In addition, hyaluronic acid-based hydrogel formed ~ 30 μm of the collageneous capsule after 8 weeks [ 13 ]. Thus, both CNC-S hydrogel and CNS-DS hydrogel showed a low level of fibrous capsule formation, similar to other biocompatible hydrogels.…”

“…Furthermore, diverse growth factors/cytokines-loaded biomaterials have been studied to induce angiogenesis inside scaffolds. For example, vascular endothelial growth factor (VEGF)-loaded, integrin-modified polyethylene glycol (PEG) hydrogels showed vascularization inside the implanted hydrogels and bone repairing a bone defect model [ 12 ], and basic fibroblast growth factor (bFGF)-loaded hyaluronic acid hydrogel allowed cellular infiltration and ingrowth of host tissues by subcutaneous implantation into rats [ 13 ]. Especially, VEGF has been known as a key factor to promote the proliferation of the endothelial cell, angiogenesis, recovery, and regeneration of tissues [ 14 , 15 ].…”

Histological Evaluation of Restylane Lyft Used as a Scaffold for Dental Pulp Regeneration in Non-Infected Immature Teeth in Dogs

“…In fact, it has been well documented in various studies that HA exhibits a fibroblast enhancement property. Its application at wound sites improved healing via the increased activity of fibroblasts and the production of collagen fibers and elastin [55][56][57][58][59]. In contradistinction to the presented results, in previously reported histological studies that tested different scaffolds while using infected models, the formation of pulp-like connective tissue was lacking, suggesting that stem cells from the apical papilla might have undergone necrosis as a result of induction from periapical infection and/or the application of a triple antibiotic paste used for canals' disinfection [32,43,54,60].…”

Recent Progress on Polysaccharide-Based Hydrogels for Controlled Delivery of Therapeutic Biomolecules

“…For example, thiol-4-arms-PEGs have been used to cross-link HA-acrylate encapsulating bFGF, to induce the formation of collagen inside the hydrogel by fibroblasts. 217 With this type of chemistry, it is also possible to add cysteine-containing peptides with different functionalities into the hydrogel, such as MMP-sensitive and cell-adhesive chains. Maleimide-HA hydrogels cross-linked with these peptides were able to sustain the release in vitro of BMP-2 and SDF-1α and were sufficient to increase bone formation.…”

“…This process does not involve the use of organic solvents and is also highly specific, which is optimal for cell encapsulation and delivery of sensitive biomolecules. For example, thiol-4-arms-PEGs have been used to cross-link HA-acrylate encapsulating bFGF, to induce the formation of collagen inside the hydrogel by fibroblasts . With this type of chemistry, it is also possible to add cysteine-containing peptides with different functionalities into the hydrogel, such as MMP-sensitive and cell-adhesive chains.…”