Synthesis and characterization of reactive poloxamer 407s for biomedical applications

Niu, Guoguang; Du, Fengyi; Song, Li; Zhang, Hongbin; Yang, Jun; Cao, Hui; Zheng, Yudong; Yang, Zhou; Wang, Guojie; Yang, Huai; Zhu, Siquan

doi:10.1016/j.jconrel.2009.04.026

Cited by 70 publications

(41 citation statements)

References 28 publications

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“…This is consistent with previous studies demonstrating measurable but modest effects of end group modification of reverse thermal gelation behavior of other amphiphilic polymers. [43] A second limitation is that the rheometer used lacked a humidified chamber and although most tests were relatively brief, the possibility of some evaporation cannot be eliminated and this may have contributed to the different gel point values measured for the 75/25 and 50/50 groups by rheology and tube inversion.…”

Section: Discussionmentioning

confidence: 99%

Formulation and characterization of poloxamine-based hydrogels as tissue sealants

2012

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In-situ crosslinkable polyethylene glycol (PEG)-based polymers play an increasing role in surgical practice as sealants that provide a barrier to fluid/gas leakage and adhesion formation. This study investigated the gelation behavior and physical properties of hydrogels formed from homogeneous and blended solutions of two acrylated poloxamines (Tetronics® T1107 and T904) of varying molecular weight and hydrophilic/lipophilic balance relative to a PEG control. Hydrogels were formed by reverse thermal gelation at physiological temperature (T1107-containing formulations) and covalent crosslinking by Michael-type addition with dithiothreitol. All poloxamine-based hydrogels exhibited thermosensitive behavior and achieved significantly reduced swelling, increased tensile properties, and increased tissue bond strength relative to the PEG hydrogel at physiological temperature. Swelling and tensile properties of all poloxamine-based hydrogels were significantly greater at 37 °C relative to 4 °C, suggesting that their improved physical properties derive from cooperative crosslinking by both noncovalent and covalent mechanisms. Poloxamine-based hydrogels were cytocompatible and underwent hydrolytic degradation over 2 to 5 weeks depending on their T1107/T904 composition. In conclusion, select poloxamine-based hydrogels possess a number of properties potentially beneficial to tissue sealant applications including substantial increase in viscosity between room/physiological temperatures, resistance to cell adhesion, and maintenance of stable volume during equilibration.

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Section: Discussionmentioning

confidence: 99%

Formulation and characterization of poloxamine-based hydrogels as tissue sealants

2012

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“…81 Despite this, the biostability properties and the too rapid degradation in aqueous environment of this hydrogels still limit their use as cellularized scaffolds in vivo. 81,129 …”

Section: Hydrogels: Suitable Micro-environments For Btementioning

confidence: 99%

Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

et al. 2017

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Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.

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“…Despite the attractive properties of P407 as a thermogelling material, there are several drawbacks for P407 hydrogels such as, weak mechanical strength due to P407's shear thinning character, rapid dissolution, and weak mucoadhesion, which has made it unfavorable for topical applications, or other areas where the gel may be affected by shear . For instance, a 20% w/w P407 formulation containing acyclovir was administered intravaginally to mice and after 3 h only half of the acyclovir administered was detected, and none was found after 6 h .…”

Section: Poloxamer 407 As a Thermogelling Materialsmentioning

confidence: 99%

“…As such, it has been widely investigated for various biomedical applications, including drug delivery, wound dressings, and cell culture . However, there are significant drawbacks for thermogelling poloxamer 407 solutions including insufficient gel strength for some applications, weak mucoadhesiveness, and rapid dissolution of the gels formed which has limited its performance, particularly in drug delivery systems . To improve gel strength, researchers have investigated blending poloxamer with other hydrophilic polymers or nanoparticles as well as chemically modifying the structure of P407.…”

Section: Introductionmentioning

confidence: 99%

Modifying the Properties of Thermogelling Poloxamer 407 Solutions through Covalent Modification and the Use of Polymer Additives

Abou‐Shamat

Calvo‐Castro

Stair

et al. 2019

Macro Chemistry & Physics

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Thermoresponsive polymers that undergo sol–gel transition in a physiological temperature range have applications in biomedical science. Poloxamer 407 (P407) is commonly used as thermogelling material and has been approved by the Food and Drug Administration (FDA) in licenced medicines. However, it has significant drawbacks which limit its performance, particularly in drug delivery systems. In order to improve these properties, the chemical structure of P407 has been modified to produce stronger gels by either conjugating P407 with other polymers or introducing inter‐micelle linkers to the terminal hydroxyl groups of P407. However, chemical modifications have several undesirable side‐effects. The change in the chemical structure makes the polymer a novel excipient, and additional safety risks are possible, requiring expensive and time‐consuming toxicity testing prior to regulatory approval. An alternative approach to covalent modification is modifying the P407 formulations with additives including hydrophilic polymers and nanoparticles, in an attempt to improve the properties of these materials. This review investigates the approaches used to modify the properties of P407 thermogelling materials, including the use of polymer additives and covalent modification. Several recommendations are made, based on efficacy and consideration of regulatory risk to guide the development of these materials toward use in real clinical applications.

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Synthesis and characterization of reactive poloxamer 407s for biomedical applications

Cited by 70 publications

References 28 publications

Formulation and characterization of poloxamine-based hydrogels as tissue sealants

Formulation and characterization of poloxamine-based hydrogels as tissue sealants

Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

Modifying the Properties of Thermogelling Poloxamer 407 Solutions through Covalent Modification and the Use of Polymer Additives

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