Periosteal Flaps Enhance Prefabricated Engineered Bone Reparative Potential

Abstract

The clinical translation of bone tissue engineering for reconstructing large bone defects has not advanced without hurdles. The in vivo bioreactor (IVB) concept may therefore bridge between bone tissue engineering and reconstructive surgery by employing the patient body for prefabricating new prevascularized tissues. Ideally, IVB should minimize the need for exogenous growth factors/cells. Periosteal tissues are promising for IVB approaches to prefabricate tissue-engineered bone (TEB) flaps. However, the significance of preserving the periosteal vascular supply has not been adequately investigated. This study assessed muscle IVB with and without periosteal/pericranial grafts and flaps for prefabricating TEB flaps to reconstruct mandibular defects in sheep. The sheep ( n = 14) were allocated into 4 groups: muscle IVB (M group; nM = 3), muscle + periosteal graft (MP group; nMP = 4), muscle + periosteal flap (MVP group; nMVP = 4), and control group ( nControl = 3). In the first surgery, alloplastic bone blocks were implanted in the brachiocephalic muscle (M) with a periosteal graft (MP) or with a vascularized periosteal flap (MVP). After 9 wk, the prefabricated TEB flaps were transplanted to reconstruct a mandibular angle defect. In the control group, the defects were reconstructed by non-prevascularized bone blocks. Computed tomography (CT) scans were performed after 13 wk and after 23 wk at termination, followed by micro-CT (µCT) and histological analyses. Both CT and µCT analysis revealed enhanced new bone formation and decreased residual biomaterial volume in the MVP group compared with control and MP groups, while the M group showed less new bone formation and more residual biomaterial. The histological analysis showed that most of the newly formed bone emerged from defect edges, but larger areas of new bone islands were found in MP and MVP groups. The MVP group showed enhanced vascularization and higher biomaterial remodeling rates. The periosteal flaps boosted the reconstructive potential of the prefabricated TEB flaps. The regenerative potential of the periosteum was manifested after the transplantation into the mechanically stimulated bony defect microenvironment.

In Vivo Bone Tissue Engineering Strategies: Advances and Prospects

“…While reviewing multiple studies related to in vivo BTE, the spectrum of biocompatible materials most commonly used for in vivo BTE typically includes the bioceramic [ 184 , 185 , 187 , 191 , 197 , 198 , 199 , 200 , 201 ], allogeneic or xenogeneic bone-derived [ 189 , 193 , 194 , 195 , 202 , 203 ], and composite scaffolds [ 190 , 204 , 205 ]. This literature review evidently demonstrates the tendency to use mechanically stable materials with long controlled biodegradation rate for in vivo BTE purposes.…”

“…Furthermore, some authors present efforts to improve properties of the scaffolds by combining various bioactive materials. Thus, Abu-Shahba used biohybrid bone blocks consisting of bovine-derived bone matrix in combination with PCL biodegradable polymer and collagen fragments for surface activation and scaffold reinforcement [ 204 ]. Kuzmenka et al presented sol-gel hybrid glass scaffold integrated with calcium sources with the aim to create a bioactive implant with long-lasting calcium release while preserving its mechanical properties [ 206 ].…”

“…Extrinsic and intrinsic vascularization modes have been widely used in the experimental and clinical studies [ 202 , 216 , 217 , 218 , 219 ]. Various tissue types have been applied for bone grafts or scaffolds prefabrication in recent years, including subcutaneous pocket, periosteal, fascial, muscular, and omental flaps [ 147 , 193 , 198 , 204 , 214 , 220 , 221 , 222 , 223 ].…”

“…Periosteal flaps have been widely used for bone grafts prefabrication due to well-known high osteogenic potential and rich vasculature of the periosteum [ 191 , 193 , 194 , 198 , 204 ]. The inner cambium layer of the periosteum is well-vascularized and represents the rich source of clinically useful osteoprogenitor cells, including osteoblasts and multipotent stem cells.…”

“…Abu-Shahba et al investigated the regenerative potential of the periosteal grafts and vascularized periosteal flaps in combination with muscle flaps in sheep model mandible defects reconstruction. The authors revealed enhanced new bone formation and enhanced vascularization after 13 and 23 weeks after alloplastic scaffolds implantation in both study groups by means of micro-CT and histological analysis [ 204 ].…”