Portal de Periódicos da CAPES

92. Intrathecal pressure, spinal cord compression and edema following traumatic spinal cord injury in a porcine model

2023; Elsevier BV; Volume: 23; Issue: 9 Linguagem: Inglês

10.1016/j.spinee.2023.06.145

1878-1632

Christine Diana Gayen, Madeleine Amy Bessen, Ryan M. Dorrian, Ryan D. Quarrington, Ryan O’Hare Doig, Anna V. Leonard, Claire F. Jones,

Periodontal Regeneration and Treatments

BACKGROUND CONTEXT Hyper-crosslinked carbohydrate polymer (HCCP) is used clinically as an osteoconductive bone graft substitute (Koleva et al., 2019). Osteoconductive materials serve as scaffolding for new bone growth that is perpetuated by the native bone adjacent to a skeletal defect site. Osteoblasts from the bone defect margin infiltrate the graft framework and generate new bone that bridges the skeletal gap. Unlike osteoconductive materials, osteoinductive materials, such as bone morphogenetic protein-2 (BMP-2), are capable of stimulating osteoprogenitor cells to differentiate into cells of osteogenic lineage, which then begin forming the new bone matrix. Osteoinductive bone graft substitutes can expedite bone regeneration at defect sites and improve clinical outcomes in patients with compromised bone healing (McKay et al., 2007). Despite efficacy in bone healing, collagen sponges infused with BMP-2 are associated with complications such as ectopic bone formation (Epstein, 2013) and anti-Bovine Collagen antibodies (18% of patients, according to Infuse IFU), which may cause complications with repeat administration. METHODS To investigate the ability of HCCP-based scaffolds to act as a BMP-2 carrier, we tested the bone-forming capacity of BMP-2 loaded HCCP-based scaffolds using rodent intermuscular implants, a method widely accepted for studies of ectopic bone formation. (Scott et al., 2012, Kirk JF, et al., 2013; Lee HR, et al., 2013; Asatrian G, et al., 2014). Test articles (HCCP-based scaffold + 75 µg rhBMP-2) or control articles (Infuse ACS + 75 µg rhBMP-2) were implanted in the intermuscular pouch of the hindlimbs of rats. Each animal received 2 implants, one per hindlimb, for a total of 3 implants per treatment group. At approximately 28 days postoperatively, animals were sacrificed in a CO2 chamber. A necropsy was performed, and implants collected for histological processing and staining with H&E, Masson's Trichrome, and Alcian Blue. Osteoinduction, osteogenic changes, and bone tissue formation were evaluated microscopically. RESULTS Histological analysis revealed the HCCP-based explants contained approximately 3 times more bone and cartilaginous tissue than the infuse explants. The infuse explants contained mature bone, but were significantly smaller, and mostly hollow. Strikingly, the HCCP-based implants were largely filled with mature bone, cartilaginous tissue and progenitor tissue, with little to no signs of inflammation. Furthermore, the HCCP-based explants showed a high degree of vascularization. CONCLUSIONS These results indicate that HCCP-based scaffolds can be used as a carrier of BMP-2, are osteoinductive and highly regenerative. FDA Device/Drug Status HCCP (Investigational/Not Approved) Hyper-crosslinked carbohydrate polymer (HCCP) is used clinically as an osteoconductive bone graft substitute (Koleva et al., 2019). Osteoconductive materials serve as scaffolding for new bone growth that is perpetuated by the native bone adjacent to a skeletal defect site. Osteoblasts from the bone defect margin infiltrate the graft framework and generate new bone that bridges the skeletal gap. Unlike osteoconductive materials, osteoinductive materials, such as bone morphogenetic protein-2 (BMP-2), are capable of stimulating osteoprogenitor cells to differentiate into cells of osteogenic lineage, which then begin forming the new bone matrix. Osteoinductive bone graft substitutes can expedite bone regeneration at defect sites and improve clinical outcomes in patients with compromised bone healing (McKay et al., 2007). Despite efficacy in bone healing, collagen sponges infused with BMP-2 are associated with complications such as ectopic bone formation (Epstein, 2013) and anti-Bovine Collagen antibodies (18% of patients, according to Infuse IFU), which may cause complications with repeat administration. To investigate the ability of HCCP-based scaffolds to act as a BMP-2 carrier, we tested the bone-forming capacity of BMP-2 loaded HCCP-based scaffolds using rodent intermuscular implants, a method widely accepted for studies of ectopic bone formation. (Scott et al., 2012, Kirk JF, et al., 2013; Lee HR, et al., 2013; Asatrian G, et al., 2014). Test articles (HCCP-based scaffold + 75 µg rhBMP-2) or control articles (Infuse ACS + 75 µg rhBMP-2) were implanted in the intermuscular pouch of the hindlimbs of rats. Each animal received 2 implants, one per hindlimb, for a total of 3 implants per treatment group. At approximately 28 days postoperatively, animals were sacrificed in a CO2 chamber. A necropsy was performed, and implants collected for histological processing and staining with H&E, Masson's Trichrome, and Alcian Blue. Osteoinduction, osteogenic changes, and bone tissue formation were evaluated microscopically. Histological analysis revealed the HCCP-based explants contained approximately 3 times more bone and cartilaginous tissue than the infuse explants. The infuse explants contained mature bone, but were significantly smaller, and mostly hollow. Strikingly, the HCCP-based implants were largely filled with mature bone, cartilaginous tissue and progenitor tissue, with little to no signs of inflammation. Furthermore, the HCCP-based explants showed a high degree of vascularization. These results indicate that HCCP-based scaffolds can be used as a carrier of BMP-2, are osteoinductive and highly regenerative.