Effect of porosity of a functionally-graded scaffold for the treatment of corticosteroid-associated osteonecrosis of the femoral head in rabbits.
Journal of orthopaedic translation
2021; 28: 90–99
Background/Objective: Core decompression (CD) with scaffold and cell-based therapies is a promising strategy for providing both mechanical support and regeneration of the osteonecrotic area for early stage osteonecrosis of the femoral head (ONFH). We designed a new 3D printed porous functionally-graded scaffold (FGS) with a central channel to facilitate delivery of transplanted cells in a hydrogel to the osteonecrotic area. However, the optimal porous structural design for the FGS for the engineering of bone in ONFH has not been elucidated. The aim of this study was to fabricate and evaluate two different porous structures (30% or 60% porosity) of the FGSs in corticosteroid-associated ONFH in rabbits.Methods: Two different FGSs with 30% or 60% porosity containing a 1-mm central channel were 3D printed using polycaprolactone and beta-tricalcium phosphate. The FGS was 3-mm diameter and 32-mm length and was composed of three segments: 1-mm in length for the non-porous proximal segment, 22-mm in length for the porous (30% versus 60%) middle segment, and 9-mm in length for the 15% porous distal segment. Eighteen male New Zealand White rabbits were given a single dose of 20mg/kg methylprednisolone acetate intramuscularly. Four weeks later, rabbits were divided into three groups: the CD group, the 30% porosity FGS group, and the 60% porosity FGS group. In the CD group, a 3-mm diameter drill hole was created into the left femoral head. In the FGS groups, a 30% or 60% porosity implant was inserted into the bone tunnel. Eight weeks postoperatively, femurs were harvested and microCT, mechanical, and histological analyses were performed.Results: The actual porosity and pore size of the middle segments were 26.4%±2.3% and 699±56mum in the 30% porosity FGS, and 56.0%±4.5% and 999±71mum in the 60% porosity FGS, respectively using microCT analysis. Bone ingrowth ratio in the 30% porosity FGS group was 73.9%±15.8%, which was significantly higher than 39.5%±13.0% in the CD group on microCT (p<0.05). Bone ingrowth ratio in the 60% porosity FGS group (61.3%±30.1%) showed no significant differences compared to the other two groups. The stiffness at the bone tunnel site in the 30% porosity FGS group was 582.4±192.3N/mm3, which was significantly higher than 338.7±164.6N/mm3 in the 60% porosity FGS group during push-out testing (p<0.05). Hematoxylin and eosin staining exhibited thick and mature trabecular bone around the porous FGS in the 30% porosity FGS group, whereas thinner, more immature trabecular bone was seen around the porous FGS in the 60% porosity FGS group.Conclusion: These findings indicate that the 30% porosity FGS may enhance bone regeneration and have superior biomechanical properties in the bone tunnel after CD in ONFH, compared to the 60% porosity FGS.Translation potential statement: The translational potential of this article: This FGS implant holds promise for improving outcomes of CD for early stage ONFH.
View details for DOI 10.1016/j.jot.2021.01.002
View details for PubMedID 33816112
Investigation of a Prevascularized Bone Graft for Large Defects in the Ovine Tibia.
Tissue engineering. Part A
In vivo bioreactors are a promising approach for engineering vascularized autologous bone grafts to repair large bone defects. In this pilot parametric study, we first developed a 3D printed scaffold uniquely designed to accommodate inclusion of a vascular bundle and facilitate growth factor delivery for accelerated vascular invasion and ectopic bone formation. Second, we established a new sheep deep circumflex iliac artery (DCIA) model as an in vivo bioreactor for engineering a vascularized bone graft and evaluated the effect of implantation duration on ectopic bone formation. Third, after 8 weeks of implantation around the DCIA, we transplanted the prevascularized bone graft to a 5 cm segmental bone defect in the sheep tibia, using the custom 3D printed BMP-2 loaded scaffold without prior in vivo bioreactor maturation as a control. Analysis by micro-computed tomography and histomorphometry found ectopic bone formation in BMP-2 loaded scaffolds implanted for 8 and 12 weeks in the iliac pouch, with greater bone formation occurring after 12 weeks. Grafts transplanted to the tibial defect supported bone growth, mainly on the periphery of the graft, but greater bone growth and less soft tissue invasion was observed in the avascular BMP-2 loaded scaffold implanted directly into the tibia without prior in vivo maturation. Histopathological evaluation noted considerably greater vascularity in the bone grafts that underwent in vivo maturation with an inserted vascular bundle compared to the avascular BMP-2 loaded graft. Our findings indicate that use of an initial DCIA in vivo bioreactor maturation step is a promising approach to developing vascularized autologous bone grafts, although scaffolds with greater osteoinductivity should be further studied.
View details for DOI 10.1089/ten.TEA.2020.0347
View details for PubMedID 33858216
Osteoinductive 3D printed scaffold healed 5cm segmental bone defects in the ovine metatarsus.
2021; 11 (1): 6704
Autologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. Recombinant human bone morphogenetic protein 2 (rhBMP-2) can stimulate bone regeneration and enhance the healing efficacy of bone grafts. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest. We here demonstrate that an osteoinductive scaffold, fabricated by combining a 3D printed rigid polymer/ceramic composite scaffold with an rhBMP-2-eluting collagen sponge can treat extremely large-scale segmental defects in a pilot feasibility study using a new sheep metatarsus fracture model stabilized with an intramedullary nail. Bone regeneration after 24weeks was evaluated by micro-computed tomography, mechanical testing, and histological characterization. Load-bearing cortical bridging was achieved in all animals, with increased bone volume observed in sheep that received osteoinductive scaffolds compared to sheep that received an rhBMP-2-eluting collagen sponge alone.
View details for DOI 10.1038/s41598-021-86210-5
View details for PubMedID 33758338
- Development of PLGA-PEG-COOH and Gelatin-Based Microparticles Dual Delivery System and E-Beam Sterilization Effects for Controlled Release of BMP-2 and IGF-1 PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION 2020
The Influence of Electron Beam Sterilization on In Vivo Degradation of beta-TCP/PCL of Different Composite Ratios for Bone Tissue Engineering.
2020; 11 (3)
We evaluated the effect of electron beam (E-beam) sterilization (25 kGy, ISO 11137) on the degradation of beta-tricalcium phosphate/polycaprolactone (beta-TCP/PCL) composite filaments of various ratios (0:100, 20:80, 40:60, and 60:40 TCP:PCL by mass) in a rat subcutaneous model for 24 weeks. Volumes of the samples before implantation and after explantation were measured using micro-computed tomography (micro-CT). The filament volume changes before sacrifice were also measured using a live micro-CT. In our micro-CT analyses, there was no significant difference in volume change between the E-beam treated groups and non-E-beam treated groups of the same beta-TCP to PCL ratios, except for the 0% beta-TCP group. However, the average volume reduction differences between the E-beam and non-E-beam groups in the same-ratio samples were 0.76% (0% TCP), 3.30% (20% TCP), 4.65% (40% TCP), and 3.67% (60% TCP). The E-beam samples generally had more volume reduction in all experimental groups. Therefore, E-beam treatment may accelerate degradation. In our live micro-CT analyses, most volume reduction arose in the first four weeks after implantation and slowed between 4 and 20 weeks in all groups. E-beam groups showed greater volume reduction at every time point, which is consistent with the results by micro-CT analysis. Histology results suggest the biocompatibility of TCP/PCL composite filaments.
View details for DOI 10.3390/mi11030273
View details for PubMedID 32155781
Development of PLGA-PEG-COOH and gelatin-based microparticles dual delivery system and E-beam sterilization effects for controlled release of BMP-2 and IGF-1.
Particle & particle systems characterization : measurement and description of particle properties and behavior in powders and other disperse systems
2020; 37 (10)
The purpose of this study was to develop a PLGA-PEG-COOH- and gelatin-based microparticles (MPs) dual delivery system for release of BMP-2 and IGF-1. We made and characterized the delivery system based on its morphology, loading capacity, Encapsulation efficiency and release kinetics. Second, we examined the effects of electron beam (EB) sterilization on BMP-2 and IGF-1 loaded MPs and their biological effects. Third, we evaluated the synergistic effect of a controlled dual release of BMP-2 and IGF-1 on osteogenesis of MSCs. Encapsulation efficiency of growth factors into gelatin and PLGA-PEG-COOH MPs are in the range of 64.78% to 76.11%. E-beam sterilized growth factor delivery systems were effective in significantly promoting osteogenesis of MSCs, although E-beam sterilization decreased the bioactivity of growth factors in MPs by approximately 22%. BMP-2 release behavior from gelatin MPs/PEG hydrogel shows a faster release (52.7%) than that of IGF-1 from the PLGA-PEG-COOH MPs/PEG hydrogel (27.3%). The results demonstrate that the gelatin and PLGA-PEG-COOH MPs based delivery system could realize temporal release of therapeutic biomolecules by incorporating different growth factors into distinct microparticles. EB sterilization was an accessible method for sterilizing growth factors loaded carriers, which could pave the way for implementing growth factor delivery in clinical applications.
View details for DOI 10.1002/ppsc.202000180
View details for PubMedID 33384477
View details for PubMedCentralID PMC7771709