Elastomeric Osteoconductive Synthetic Scaffolds with Acquired Osteoinductivity Expedite the Repair of Critical Femoral Defects in Rats

Abstract

Regenerative medicine aspires to reduce reliance on or overcome limitations associated with donor tissuemediated repair. Structural bone allografts are commonly used in orthopedic surgery, with a high percentage of graft failure due to poor tissue integration. This problem is aggravated among elderly, those suffering from metabolic conditions, or those undergoing cancer therapies that compromise graft healing. Toward this end, we developed a synthetic graft named FlexBone, in which nanocrystalline hydroxyapatite (50 wt%) was structurally integrated with crosslinked poly(hydroxyethyl methacrylate) hydrogel, which provides dimensional stability and elasticity. It recapitulates the essential role of nanocrystalline hydroxyapatite in defining the osteoconductivity and biochemical microenvironment of bone because of its affinity for biomolecules. Here, we demonstrate that FlexBone effectively absorbed endogenously secreted signaling molecules associated with the inflammation/graft healing cascade upon being press-fit into a 5-mm rat femoral segmental defect. Further, when preabsorbed with a single dose of 400 ng recombinant human (rh) bone morphogenetic protein-2/7 heterodimer, it enabled the functional repair of the critical-sized defect by 8-12 weeks. FlexBone was stably encapsulated by the bridging bony callus and the FlexBone-callus interface was continuously remodeled. In summary, FlexBone combines the dimensional stability and osteoconductivity of structural bone allografts with desirable surgical compressibility and acquired osteoinductivity in an easy-to-fabricate and scalable synthetic biomaterial.

Vancomycin-bearing Synthetic Bone Graft Delivers rhBMP-2 and Promotes Healing of Critical Rat Femoral Segmental Defects

“…When loaded with a single dose of 400 ng recombinant human bone morphogenetic protein-2/7 heterodimer (rhBMP-2/7) and press-fit into a 5-mm rat femoral segmental defect, the composite facilitated both the formation of fully bridged bony callus in 8 to 12 weeks and the restoration of torsional rigidity by 12 weeks [8]. Furthermore, up to 4.8 wt% vancomycin can be encapsulated within pHEMA-nHA without significantly compromising the structural integrity or the elasticity of the composite graft [17].…”

Can Normal Fracture Healing Be Achieved When the Implant Is Retained on the Basis of Infection? An Experimental Animal Model

“…Torque to failure and stiffness both were lower in the infection group than in the control group at 6 weeks, but with the numbers available for testing, they were not different at 3 weeks (p = 0.615 and p = 1, respectively; Table 2 [3][4][5][6][7][8][9][10][11][12][13][14][15][16]; p = 0.004) both were greater in the control group than in the group with infection. Maximum torque to failure was lower in the infection group than in the control group at all time points.…”

“…Rat osteosynthesis models have previously used open incisions and stabilization with plates or external fixator systems [4,8,9,17]. Although these systems are commonly associated with gap osteotomy models, a fracture model could be similarly achieved by making a single saw cut (rather than two needed for a gap osteotomy).…”

“…Results Infection decreased callus strength at 6 weeks. Torque to failure (299.07 ± 65.53 Nmm versus 107.20 ± 88.81, mean difference with 95% confidence interval, 192 ; p = 0.007) and stiffness at 6 weeks (11.28 ± 2.67 Nmm versus 2.03 ± 1.68, mean difference with 95% confidence interval, 9 [3][4][5][6][7][8][9][10][11][12][13][14][15][16]; p = 0.004) both were greater in the control group than in the group with infection.…”

Scalable Functional Bone Substitutes: Strategic Integration of Key Structural Elements of Bone in Synthetic Biomaterials

“…Thus, HA has long been recognized as an important design element for tissue-engineered bone substitutes (El-Ghannam, 2005). The intrinsic affinity of the dynamic apatite crystal surfaces for many acidic non-collagenous proteins widely found in calcified tissues (George et al, 1996;Gilbert et al, 2000;Stubbs et al, 1997) have also inspired the use of bioceramic scaffolds (Le Nihouannen et al, 2008) or polymer-bioceramics composite scaffolds (Abarrategi et al, 2008;Filion et al, 2011;Xu et al, 2009) to retain and deliver recombinant proteins for therapeutic uses. Overall, HA has been explored for bone tissue engineering applications more as a way to enhance the mechanical strength than as a tool to mediate the biochemical properties of the scaffold (Stevens, 2008;.…”