Cell-Laden and Cell-Free Biopolymer Hydrogel for the Treatment of Osteochondral Defects in a Sheep Model

Abstract

The objective of the current study was to determine the suitability of cell-laden and cell-free alginate-gelatin biopolymer hydrogel for osteochondral restoration in a sheep model (n = 12). Four femoral defects per animal were filled with hydrogel (cHG) plus autologous chondrocytes (cHG + C) or periosteal cells (cHG + P) or gel only (cHG) or were left untreated (E). In situ solidification enabled instantaneous implant fixation. Sixteen weeks postoperatively, defect sites were processed for light microscopy and immunofluorescence. A modified Mankin and a semi-quantitative immunoreactivity score were used to evaluate histology and immunofluorescence, respectively. Defects after cHG + C were restored with smooth, hyaline-like neo-cartilage and trabecular subchondral bone. cHG + P and cHG treatments revealed slightly inferior regenerate morphology. Undifferentiated tissue was found in E. The histological score showed significant (p < 0.05) differences between all treatment groups. In conclusion, cHG induces satisfactory defect regeneration. Complete filling of the cavity in one step and subsequent rapid in situ solidification was feasible and facilitated graft fixation. Cell implantation might be beneficial, because cells seem to play a key role in histological outcome. Still, their contribution to the repair process remains unresolved because host cell influx takes place. The combination of alginate and gelatin, however, creates an environment capable of serving implanted and host cells for osteo-chondrogenic tissue regeneration.

In SituTissue Regeneration: Chemoattractants for Endogenous Stem Cell Recruitment

“…[29][30][31][32] Approaches under development use chemoattactants to enhance migration of endogenous MSC to accelerate wound healing and/or colonize biomaterial scaffolds. [33][34][35] Recent proof of concept studies demonstrating tissue regeneration by endogenous MSC recruitment have motivated further development of this approach. [36][37][38] The most effective chemoattractants for recruiting endogenous MSC may vary with tissue type and remain to be determined.…”

Bilayer Implants

“…However, it is crucial to establish critical size defects as they do not heal spontaneously. 25,34,35 Our own observations are partly inconsistent: our previous hydrogel study on mature sheep demonstrated that untreated critical size osteochondral defects (diameter: 6 mm, depth: 12 mm) were not restored properly, 36 whereas even larger untreated osteochondral defects (diameter: 8 mm, depth: 13 mm) in another study also on mature sheep showed a healing response (submitted). In order to avoid lesion size as a factor of uncertainty, a decision was made for vast osteochondral defects (width: 6 mm, length: 20 mm, maximum depth: 5 mm).…”

Oligo[poly(ethylene glycol)fumarate] Hydrogel Enhances Osteochondral Repair in Porcine Femoral Condyle Defects

“…More than 90% tissue filling was also noted in 2.4-mm [63] and 3.7-mm [41] defects of the rabbit model, which were left untreated for 2 and 3 months, respectively. However, osteochondral defects implanted with hydrogel scaffolds generally have incomplete filling in large animals [14,48]. Differences in repair could be attributed to different intrinsic spontaneous healing capacities between species, as shown by Kon et al who reported the implantation of the same collagen-hydroxyapatite scaffold into sheep [35] and equine [37] models generated inferior fibrocartilaginous tissue in the largersized animal.…”