Periosteum‐derived mesenchymal progenitor cells in engineered implants promote fracture healing in a critical‐size defect rat model

Abstract

An attractive alternative to bone autografts is the use of autologous mesenchymal progenitor cells (MSCs) in combination with biomaterials. We compared the therapeutic potential of different sources of mesenchymal stem cells in combination with biomaterials in a bone nonunion model. A critical‐size defect was created in Sprague–Dawley rats. Animals were divided into six groups, depending on the treatment to be applied: bone defect was left empty (CTL); treated with live bone allograft (LBA); hrBMP‐2 in collagen scaffold (CSBMP2); acellular polycaprolactone scaffold (PCL group); PCL scaffold containing periosteum‐derived MSCs (PCLPMSCs) and PCL containing bone marrow‐derived MSCs (PCLBMSCs). To facilitate cell tracking, both MSCs and bone graft were isolated from green fluorescent protein (GFP)‐transgenic rats. CTL group did not show any signs of healing during the radiological follow‐up (n = 6). In the LBA group, all the animals showed bone bridging (n = 6) whereas in the CSBMP2 group, four out of six animals demonstrated healing. In PCL and PCLPMSCs groups, a reduced number of animals showed radiological healing, whereas no healing was detected in the PCLBMSCs group. Using microcomputed tomography, the bone volume filling the defect was quantified, showing significant new bone formation in the LBA, CSBMP2, and PCLPMSCs groups when compared with the CTL group. At 10 weeks, GFP positive cells were detected only in the LBA group and restricted to the outer cortical bone in close contact with the periosteum. Tracking of cellular implants demonstrated significant survival of the PMSCs when compared with BMSCs. In conclusion, PMSCs improve bone regeneration being suitable for mimetic autograft design.

Polycaprolactone as biomaterial for bone scaffolds: Review of literature

“…However, at 10 weeks, green fluorescent protein positive cells were detected only in LBA group in the outer cortical bone in close contact with the periosteum. 86 Nguyen 2019 conjugated a 'smart' Poly N-isopropyl acrylamide to fabricate PCL bead surfaces to serve as a thermo-responsive macrocarrier for non-invasive detachment of cells, and allowed human dermal fibroblasts and mesenchymal stem cells to adhere, and proliferate. 87 Fuchs (2019) developed PCL scaffolds via melt electrospinning writing (MEW), and core membrane via film casting.…”

Intraosteal Behavior of Porous Scaffolds: The mCT Raw-Data Analysis as a Tool for Better Understanding

“…These results can be partially compared to those showed by Sweedy et al (2017) [22], who defined a scaffold resorption ratio of 22.16 ± 3.3%-31.66 ± 6.8% for a 6 weeks study period using Swiss Alpine sheep. However, it must be taken into account that this resorption ratio not only depends on animal species, but also is affected by scaffold porous size, implant composition or scaffold total size [37][38][39]. Furthermore, Bohner et al (2017) [21] described that scaffold resorption and bone/mineralized tissue formation is not a uniform process, with a rapid increase in the first 4-10 weeks followed by a slow decrease after 10-12 weeks post-implantation.…”

“…This would lead to the refinement of experiments, due to the reduction of the number of animals needed, and to the continuous data collection without the need for animal sacrifice at intermediate experimental points [37]. Regarding in vivo assessment of bone quality and regeneration, preclinical research requires the combination of image and histomorphometric analysis [37][38][39][40]. Against visual image analysis and volumetric estimation of average standardized X-ray attenuation coefficients, histology provides a direct method to assess the bone regeneration process at a macroscopic and microscopic level, without resolution or standardization limitations.…”

Periosteum progenitors could stimulate bone regeneration in aged murine bone defect model

“…9,10 In general, osteogenic progenitors distribute in various bone compartments along the bone's outer surface within the periosteum and the inner surface of bone within the endosteum. 11,12 Histological, periosteum is composed of at least two layers, outer fibrous layer and inner cambium layer. 13 The outer fibrous layer mainly contains fibroblastic cells, while the inner cambium layer contains several types of cells, such as fibroblasts, mesenchymal stem cells, osteogenic or chondrogenic progenitors.…”

“…Both procedures require the replenishment of the osteogenic or chondrogenic progenitor cells that participate in bone or cartilage formation during normal development and under pathologic conditions, such as fracture healing 9,10 . In general, osteogenic progenitors distribute in various bone compartments along the bone's outer surface within the periosteum and the inner surface of bone within the endosteum 11,12 . Histological, periosteum is composed of at least two layers, outer fibrous layer and inner cambium layer 13 .…”