Pathology of Bioabsorbable Implants in Preclinical Studies.

Bioabsorbable implants can be advantageous for certain surgical tissue bioengineering applications and implant-assisted tissue repair. They offer the obvious benefits of nonpermanence and eventual restoration of the native tissue's biomechanical and immunological properties, while providing a structural scaffold for healing and a route for additional therapies (i.e., drug elution). They present unique developmental, imaging, and histopathological challenges in the conduct of preclinical animal studies and in interpretation of pathology data. The bioabsorption process is typically associated with a gradual decline (over months to years) in structural strength and integrity and may also be associated with cellular responses such as phagocytosis that may confound interpretation of efficacy and safety end points. Additionally, as these implants bioabsorb, they become increasingly difficult to isolate histologically and thus imaging modalities such as microCT become very valuable to determine the original location of the implants and to assess the remodeling response in tandem with histopathology. In this article, we will review different types of bioabsorbable implants and commonly used bioabsorbable materials; additionally, we will address some of the most common challenges and pitfalls confronting histologists and pathologists in collecting, handling, imaging, preparing tissues through histology, evaluating, and interpreting study data associated with bioabsorbable implants.

The biointegration profile of fiber-reinforced plates following tibial implantation in sheep.

Biointegrative, mineral fiber-reinforced bone fixation implants recently introduced in orthopedic surgery have expanded available treatment options for fractures and bone deformities. This new technology aims to address the disadvantages of permanent metallic implants while overcoming inherent concerns of adverse inflammatory reactions when using polymer-based orthopedic implants. The purpose of this double-arm preclinical study was to evaluate the safety, biocompatibility, and biointegration of fiber-reinforced plates, following implantation on the tibias of eight sheep. Left tibias underwent periosteal elevation, allowing for implant attachment directly onto the cortical surface; right tibia plates were implanted over intact periosteum. Microcomputed tomography and histopathology were performed at 13, 26, 52, 78, 104, and 134 weeks postimplantation. All animals were evaluated clinically at each time point, with no evidence of local adverse reactions. Histopathology demonstrated anti-inflammatory M2-like macrophages and multinucleated giant cells corresponding to implant bioabsorption, similar for both groups at each time point, and indicating expected implant biocompatibility. Inflammatory cells (i.e., eosinophils, lymphophyctes, plasma cells, and M1-like macrophages) were absent throughout the study. The bioabsorption process had started at 13 W, with the highest rate at 52-78 W. At 104 W, only residual polymer material was left (∼5% of implant area). Low amounts of mineral fibers were evident at 78 W and were absent (fully remodeled) by 104 W. At 134 W, implants at both sites were fully bioabsorbed. In conclusion, these new fiber-reinforced implants demonstrated bone remodeling and complete biointegration, with no adverse tissue response. Clinical significance: In this double-arm, 2.5-year study, a biointegrative, fiber-reinforced plate implanted on the tibias of sheep was fully absorbed within 134 weeks, with no adverse tissue reaction. Bioabsorption was similar, with or without periosteal elevation, mimicking conditions like those observed in traumatic injuries disrupting the periosteum, open reduction and internal fixation, or minimally invasive surgeries. These results demonstrate the feasibility, versatility, and safety of this new class of biointegrative bone implants. This newly developed technology avoids the complications of the removal of metal implants.

Geometric Mismatch Promotes Anatomic Repair in Periorbital Bony Defects in Skeletally Mature Yucatan Minipigs.

Porous tissue-engineered 3D-printed scaffolds are a compelling alternative to autografts for the treatment of large periorbital bone defects. Matching the defect-specific geometry has long been considered an optimal strategy to restore pre-injury anatomy. However, studies in large animal models have revealed that biomaterial-induced bone formation largely occurs around the scaffold periphery. Such ectopic bone formation in the periorbital region can affect vision and cause disfigurement. To enhance anatomic reconstruction, geometric mismatches are introduced in the scaffolds used to treat full thickness zygomatic defects created bilaterally in adult Yucatan minipigs. 3D-printed, anatomically-mirrored scaffolds are used in combination with autologous stromal vascular fraction of cells (SVF) for treatment. An advanced image-registration workflow is developed to quantify the post-surgical geometric mismatch and correlate it with the spatial pattern of the regenerating bone. Osteoconductive bone growth on the dorsal and ventral aspect of the defect enhances scaffold integration with the native bone while medio-lateral bone growth leads to failure of the scaffolds to integrate. A strong positive correlation is found between geometric mismatch and orthotopic bone deposition at the defect site. The data suggest that strategic mismatch >20% could improve bone scaffold design to promote enhanced regeneration, osseointegration, and long-term scaffold survivability.