Growth Factor Delivery for the Repair of a Critical Size Tibia Defect Using an Acellular, Biodegradable Polyethylene Glycol–Albumin Hydrogel Implant

Abstract

Growth factor delivery using acellular matrices presents a promising alternative to current treatment options for bone repair in critical-size injuries. However, supra-physiological doses of the factors can introduce safety concerns that must be alleviated, mainly by sustaining delivery of smaller doses using the matrix as a depot. We developed an acellular, biodegradable hydrogel implant composed of poly­(ethylene glycol) (PEG) and denatured albumin to be used for sustained delivery of bone morphogenic protein-2 (BMP2). In this study, poly­(ethylene glycol)–albumin (PEG-Alb) hydrogels were produced and loaded with 7.7 μg/mL of recombinant human BMP2 (rhBMP2) to be tested for safety and performance in a critical-size long-bone defect, using a rodent model. The hydrogels were formed ex situ in a 5 mm long cylindrical mold of 3 mm diameter, implanted into defects made in the tibia of Sprague–Dawley rats and compared to non-rhBMP2 control hydrogels at 13 weeks following surgery. The hydrogels were also compared to the more established PEG–fibrinogen (PEG-Fib) hydrogels we have tested previously. Comprehensive in vitro characterization as well as in vivo assessments that include: histological analyses, including safety parameters (i.e., local tolerance and toxicity), assessment of implant degradation, bone formation, as well as repair tissue density using quantitative microCT analysis were performed. The in vitro assessments demonstrated similarities between the mechanical and release properties of the PEG-Alb hydrogels to those of the PEG-Fib hydrogels. Safety analysis presented good local tolerance in the bone defects and no signs of toxicity. A significantly larger amount of bone was detected at 13 weeks in the rhBMP2-treated defects as compared to non-rhBMP2 defects. However, no significant differences were noted in bone formation at 13 weeks when comparing the PEG-Alb-treated defects to PEG-Fib-treated defects (with or without BMP2). The study concludes that hydrogel scaffolds made from PEG-Alb containing 7.7 μg/mL of rhBMP2 are effective in accelerating the bridging of boney defects in the tibia.

Review of a new bone tumor therapy strategy based on bifunctional biomaterials

“…[58][59][60][61][62][63][64] Bioactivity, biocompatibility, and biodegradability are critical concerns in scaffold design, playing an important role in bone regeneration. [65][66][67][68] In particular, the key parameters of porosity, stiffness, and viscoelasticity can regulate cell adhesion, cell proliferation, and osteogenesis differentiation. [69][70][71][72][73][74][75][76] Scaffolds provide cells with sustainable regenerative factors, provide physical and biological support, and mobilize stem cells to regenerate the defect cavity.…”

Addressing the Needs of the Rapidly Aging Society through the Development of Multifunctional Bioactive Coatings for Orthopedic Applications

“…Several research groups have combined antimicrobial and osteointegrative activity into a single coating system in order to develop solutions that might aid in preventing aseptic implant loosening, a common cause of orthopedic revisions worldwide. A promising approach to enhancing implant fixation is the application of osteoinductive growth factors that promote new bone formation [ 238 , 239 ]. Bone morphogenetic protein 2 (BMP-2) is probably the most widely present osteoinductive growth factor in the development of bioactive coatings since it has obtained clinical approval [ 240 ].…”

A review of biomimetic scaffolds for bone regeneration: Toward a cell‐free strategy

“…The hydrogels were first mixed with photoinitiator stock solution, then cross-linked with rhBMP2, followed by exposure to UV light. The rhBMP2-containingd hydrogels can promote the bridging of bone defects through rhBMP2 delivery [186]. PRF, comprising abundant growth factors and immune cells can be engineered onto hydrogels for bone regeneration.…”

“…Both hydrogels with rhBMP‐2 had similar effects on bone formation and repair, repairing a 5 mm gap in the tibia simultaneously with hydrogel resorption from the defect site (Figure 13b). Furthermore, rhBMP‐2 exhibited sustained delivery through the biodegradable hydrogel while bone formation coincided with its removal from the defect locale 180 . In contrast to a single growth factor with potentially limited effects, it is possible that a combination of bioactive factors acting on osteoinduction can not only amplify the effects but possibly also abate adverse effects.…”