Evaluation of Bone Regeneration with an Injectable, In Situ Polymerizable Pluronic^® F127 Hydrogel Derivative Combined with Autologous Mesenchymal Stem Cells in a Goat Tibia Defect Model

Abstract

In situ forming bone substitute materials are attractive candidates for filling irregularly shaped defects. In this study, a chemically modified form of the Pluronic F127 hydrogel was used. Similar to the parent form, this derivative underwent a sol-gel transition in the body and additional radical curing resulted in a stable three-dimensional network gel with a controllable degradation rate. An extra cell source of autologous bone marrow-derived mesenchymal stem cells was mixed with the hydrogel to increase the ossification process, when implanted in noncritical size unicortical tibia defects. These cells were cultured and predifferentiated on two types of cell carrier systems, that is, gelatin CultiSpher-S microcarriers and hydroxyapatite tubular carriers. Radiographic and histological evaluation revealed that bone regeneration was comparable in the defects with the bone substitute compositions and the untreated control defects at 2 and 4 weeks postimplantation and that newly formed bone originated from the cells on the CultiSpher-S carriers. This resulted, 6 and 8 weeks postimplantation, in faster bone repair in the defects filled with the hydrogel plus CultiSpher-S carriers in comparison to the control defects. Surprisingly, there was no formation of new bone originating from the hydroxyapatite carriers. The hydrogel by itself seemed to stimulate the natural repair process.

An in situ gelling system for bone regeneration of osteochondral defects

“…The t 50% , the time at which the weight of the hydrogels is one half of the initial weight, is 2 h for the samples at lower calcium and medium and high HA content (HA 10 …”

“…In some cases, http://dx.doi.org/10.1016/j.eurpolymj.2015.02.043 0014-3057/Ó 2015 Elsevier Ltd. All rights reserved. the polymer component is mixed with mineral (bone substitute) materials [6,7]; in some other cases, autologous bone marrow are exploited [8][9][10]: since bone marrow contains osteochondral progenitor cells and bioactive agents, it can be supposed that the combination of scaffolds or hydrogels and bone marrow would be a superior composite material for osteochondral repair.…”

Stimuli-Responsive InjectableIn situ-Forming Hydrogels for Regenerative Medicines

“…165 In situ-forming poloxamer and pluronic hydrogels have been widely used in medical, pharmaceutical, and cosmetic applications. [166][167][168][169][170][171][172][173][174][175][176][177] Potential drawbacks include their weak mechanical strength and limited stability owing to short hydrogel residence times (∼2 days), and high permeabilities, which are unsuitable for long-term in vivo applications. [178][179][180] These disadvantages originate in the characteristics of the micellar mode of association that causes the structure to erode easily owing to dissolution from the surface in the presence of excess water.…”

Use of Native Bovine Bone Morphogenetic Protein Extract in Healing Segmental Tibial Bone Defects in Goats

“…This model is valid in studying osteo-inductive agents when the defect is too large to heal spontaneously [5]. The tibia bone defect model has been used to test bone substitute by many researchers [6,7]. DBM combined with BMP either extracted from bone tissues or produced by gene therapy and engineering has been shown to be effective in the reconstruction and repair of bone defects [8][9][10][11][12][13][14].…”