Citrate‐based biphasic scaffolds for the repair of large segmental bone defects

Abstract

Attempts to replicate native tissue architecture have lead to the design of biomimetic scaffolds focused on improving functionality. In this study, biomimetic citrate-based poly (octanediol citrate) – click hydroxyapatite (POC-Click-HA) scaffolds were developed to simultaneously replicate the compositional and architectural properties of native bone tissue while providing immediate structural support for large segmental defects following implantation. Biphasic scaffolds were fabricated with 70% internal phase porosity and various external phase porosities (between 5–50%) to mimic the bimodal distribution of cancellous and cortical bone, respectively. Biphasic POC-Click-HA scaffolds displayed compressive strengths up to 37.45 ± 3.83 MPa, which could be controlled through the external phase porosity. The biphasic scaffolds were also evaluated in vivo for the repair of 10-mm long segmental radial defects in rabbits and compared to scaffolds of uniform porosity as well as autologous bone grafts after 5, 10, and 15 weeks of implantation. The results showed that all POC-Click-HA scaffolds exhibited good biocompatibility and extensive osteointegration with host bone tissue. Biphasic scaffolds significantly enhanced new bone formation with higher bone densities in the initial stages after implantation. Biomechanical and histomorphometric analysis supported a similar outcome with biphasic scaffolds providing increased compression strength, interfacial bone ingrowth, and periosteal remodeling in early time points, but were comparable to all experimental groups after 15 weeks. These results confirm the ability of biphasic scaffold architectures to restore bone tissue and physiological functions in the early stages of recovery, and the potential of citrate-based biomaterials in orthopedic applications.

Citrate-Based Biomaterials and Their Applications in Regenerative Engineering

“…Given the strong and osteogenic characteristics of POC-Click-HA composites, this new generation of CBB composites has been used to repair large segmental defects. To mimic the bimodal distribution of cancellous and cortical bone, biomimetic biphasic POC-Click-HA scaffolds have been developed with 70% internal phase porosity and various external phase porosities (between 5% and 50%) (97). Compared with scaffolds of uniform porosity as well as autologous bone grafts, the biphasic scaffolds display excellent osteointegration, enhanced new-bone formation, higher bone densities, and improved biomechanical support in the initial stages after implantation to repair 10-mm-long segmental radial defects in rabbits.…”

A fast degradable citrate-based bone scaffold promotes spinal fusion

“…2, 19, 22 From radiography, μ-CT and histological evaluations, the scaffolds did not release toxic degradation products (Figure 5, 6, and 7) during degradation but promoting bone regeneration.…”

“…15–17 Our recent exciting findings further showed that exogenous citrates enhance alkaline phosphatase (ALP) and osterix (OSX) gene expression in C2C12 cells, a mouse myoblast cell line that can differentiate into osteoblasts, 18 and promote the mineralization of osteoblastic differentiated human mesenchymal stem cells (hMSCs). 19 A series of citrate-based biodegradable composites have recently been developed for bone regeneration, such as poly(1,8-octanediol citrate)-hydroxyapatite (POC-HA), 20, 21 clickable POC-HA (POC-click-HA), 2, 22 crosslinked urethane-doped polyesters-HA (CUPE-HA), 2 citrate-based polymer blends-HA (CBPBHA), 18 poly(ethylene glycol) maleate citrate-HA (PEGMC-HA), 23 and injectable citrate-based mussel-inspired tissue bioadhesives HA composite (iCMBA-HA). 19 The above citrate-based biomaterials have demonstrated impressive in vivo performance in various animal models for bone regeneration such as POC-click-HA for long segmental radial bone regeneration in rabbits, 22 CUPE-HA and POC-click-HA for calvarial regeneration in rats, 2 and iCMBA-HA for comminuted radial bone regeneration in rabbits.…”

“…19 A series of citrate-based biodegradable composites have recently been developed for bone regeneration, such as poly(1,8-octanediol citrate)-hydroxyapatite (POC-HA), 20, 21 clickable POC-HA (POC-click-HA), 2, 22 crosslinked urethane-doped polyesters-HA (CUPE-HA), 2 citrate-based polymer blends-HA (CBPBHA), 18 poly(ethylene glycol) maleate citrate-HA (PEGMC-HA), 23 and injectable citrate-based mussel-inspired tissue bioadhesives HA composite (iCMBA-HA). 19 The above citrate-based biomaterials have demonstrated impressive in vivo performance in various animal models for bone regeneration such as POC-click-HA for long segmental radial bone regeneration in rabbits, 22 CUPE-HA and POC-click-HA for calvarial regeneration in rats, 2 and iCMBA-HA for comminuted radial bone regeneration in rabbits. 19 However, none of citrate-based biodegradable composites have been optimized and evaluated for spinal fusion applications.…”

“…2, 22 However, click reaction resulted in rigid triazole rings, which delayed the degradation of POC-click when compared with normal POC. 24–26 …”