Autologous cell-coated particles for the treatment of segmental bone defects—a new cell therapy approach

Abstract

Background Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are one of the most potent adult stem cells, capable of differentiating into bone, cartilage, adipose, muscle, and others. An innovative autologous AT-MSC-derived cell-based product (BonoFill-II) for bone tissue regeneration was developed to be suited as a bone graft for segmental bone defects. Methods BonoFill-II was transplanted into 8 sheep with 3.2-cm full cortex segmental defect formed in the tibia. Bone regeneration was followed by X-ray radiographs for 12 weeks. At experiment termination, the healed tibia bones were analyzed by computed tomography, histology, and mechanical tests. Results Our results indicate that one dose of BonoFill-II injectable formula led to an extensive bone growth within the transplantation site and to a complete closure of the critical gap in the sheep’s tibia in a relatively short time (8–12 weeks), with no inflammation and no other signs of graft rejection. This new and innovative product opens new prospects for the treatment of long bone defects. Conclusions Injection of BonoFill-II (an innovative autologous cell therapy product for bone tissue regeneration) into a critical size segmental defect model (3.2 cm), generated in the sheep tibia, achieved full bridging of the gap in an extremely short period (8–12 weeks).

Biocompatibility of Biomaterials for Tissue Regeneration or Replacement

“…In fact, cells sourced from patients were used directly to print specific tissue sections even cartilage specific ECM or bone implants (grown from patients' fat cells). [73,74] Most recently decellularized (cells removed from a tissue explant to obtain natural and pure ECM) tissue-based hydrogels have been synthesized (embedded with cardiomyocytes) into bio-ink and used for printing organs, such as a human heart (Figure 5B). [75] A key reason for using the native ECM to synthesize the bio-ink is that, native ECM provides suitable cues and signals for cellular function and tissue formation that are often difficult to reproduce using individual ECM components like collagen and fibrin.…”

An overview of de novo bone generation in animal models

“…[225][226][227] This, in addition to similarity in weight to adult humans, lends itself to testing of three-dimensional printed grafts with varied microstructure and composition. [109][110][111][112]…”

“…The ovine tibial diaphysis has a relatively simple cylindrical macrostructure and loading mechanism compared to more structurally complex bones 225‐227 . This, in addition to similarity in weight to adult humans, lends itself to testing of three‐dimensional printed grafts with varied microstructure and composition 109‐112 …”

“…As mentioned above, lapin tibial loading is closer to human than other small mammals, so the lapin tibial mid‐diaphyseal segmental defect model, typically stabilized with a bone plate, may have the strongest translational value 49,52,53,108 . In a large animal model, ovine tibial defects of 30 mm or more in the mid‐diaphysis are often treated with plates or external fixators and monitored by standard means up to 3 to 12 months followed by histology and mechanical testing 4,109‐112,224 . The ovine tibial diaphysis has a relatively simple cylindrical macrostructure and loading mechanism compared to more structurally complex bones 225‐227 .…”

“…49,52,53,108 In a large animal model, ovine tibial defects of 30 mm or more in the mid-diaphysis are often treated with plates or external fixators and monitored by standard means up to 3 to 12 months followed by histology and mechanical testing. 4,[109][110][111][112]224 The ovine tibial diaphysis has a relatively simple cylindrical macrostructure and loading mechanism compared to more structurally complex bones. [225][226][227] This, in addition to similarity in weight to adult humans, lends itself to testing of three-dimensional printed grafts with varied microstructure and composition.…”