Lee SW, et al. Hip Pelvis. 2021 Jun;33(2):53-61. https://doi.org/10.5371/hp.2021.33.2.53

Bone regeneration remains difficult due to the complex bone microenvironment and the limited healing capacity of large defects. Biomimetic strategies offer promising solutions by using advanced 3D scaffolds guided by natural tissue cues. Recent advances in additive manufacturing, nanotechnology, and tissue engineering now allow the fabrication of hierarchical scaffolds that closely mimic native bone. Smart scaffold systems combine materials with biochemical and mechanical signals. These features improve vascularization, enhance tissue integration, and support better regenerative outcomes. Bio-inspired materials also help connect inert implants with living tissues by promoting vascular network formation and improving cell communication. Multiscale design approaches recreate bone nano- to macro-level structure and support both osteogenic activity and immune regulation. Intelligent and adaptive scaffolds are being developed to respond to physiological changes and enable personalized bone repair. This review discusses the current landscape of biomimetic scaffold design, fabrication techniques, material strategies, biological mechanisms, and translational considerations shaping next-generation bone regeneration technologies. Future directions focus on sustainable, clinically translatable biomimetic systems that can integrate with digital health tools for improved treatment planning.

The rising demand for organ transplants and the need for precise tissue models have positioned the in vitro biomanufacturing of tissues and organs as a pivotal area in regenerative treatment. Considerable development has been achieved in growing tissue-engineered intervertebral disc (IVD) scaffolds, designed to meet stringent mechanical and biological compatibility criteria. Among the cutting-edge approaches, 3D bioprinting stands out due to its unparalleled capacity to organize biomaterials, bioactive molecules, and living cells with high precision. Despite these advancements, polymer-based scaffolds still encounter limitations in replicating the extracellular matrix (ECM)-like environment, which is fundamental for optimal cellular activities. To overcome these challenges, integrating polymers with hydrogels has been recommended as a promising solution. This combination enables the advancement of porous scaffolds that nurture cell adhesion, proliferation, as well as differentiation. Additionally, bioinks derived from the decellularized extracellular matrix (dECM) have exhibited potential in replicating biologically relevant microenvironments, enhancing cell viability, differentiation, and motility. Hydrogels, whether derived from natural sources involving collagen and alginate or synthesized chemically, are highly valued for their ECM-like properties and superior biocompatibility. This review will explore recent advancements in techniques and technologies for IVD regeneration. Emphasis will be placed on identifying research gaps and proposing strategies to bridge them, with the goal of accelerating the translation of IVDs into clinical applications.

The purpose of this study was to investigate the initiation of autophagy activation and apoptosis in nucleus pulposus cells under temporary compression (TC) and sustained compression (SC) to identify ideal research approaches in intervertebral disc degeneration. Various techniques were used: radiography (X-ray), magnetic resonance imaging (MRI), transmission electron microscope (TEM), H&E staining, Masson’s trichrome staining, immunohistochemistry (IHC) (LC3, beclin-1, and cleaved caspase-3), and real-time polymerase chain reaction (RT-qPCR) for autophagy-related (beclin-1, LC3, and P62) and apoptosis-related (caspase-3 and PARP) gene expression analysis. X-ray and MRI revealed varying degrees of disc degeneration, ranging from moderate to severe in both groups. The severity was directly linked to compression duration, with SC resulting in notably severe central NP cell degeneration. Surprisingly, TC also caused similar, though less severe, degeneration. Elevated expression of LC3 and beclin-1 was identified after 6 weeks, but it notably declined after 12 weeks. Central NP cells in both groups exhibited increased expression of cleaved caspase-3 that was positively correlated with the duration of SC. TC showed fewer apoptotic markers compared to SC. LC3, beclin-1, and P62 mRNA expression peaked after 6 weeks and declined after 12 weeks in both groups. Cleaved caspase-3 and PARP expression peaked in SC, positively correlating with longer compression duration, while TC showed lower levels of apoptosis gene expression. Furthermore, TEM results revealed different events of the autophagic degradation process after 2 weeks of compression. TCmay be ideal for studying early triggered autophagy-mediated degeneration, while SC may be ideal for studying late or slower-triggered apoptosis-mediated degeneration.

Poly (methyl methacrylate) (PMMA) bone cement is widely used in percutaneous vertebroplasty to stabilize osteoporotic vertebral compression fractures. However, its clinical application is limited by its high compressive modulus, risk of thermal necrosis, and poor bone integration, unlike conventional PMMA formulations used in vertebrae or joint arthroplasty, which can reach polymerization temperatures exceeding 100 °C. Spine-specific PMMA is formulated to cure at a reduced polymerization temperature, thereby minimizing the rise in core temperature during the setting process. Consistent with our hypothesis, this moderate thermal output induces localized thermal injury that triggers osteogenic responses and extracellular matrix production, thereby enhancing osteoblast activity in the surrounding bone. This study aimed to evaluate bone remodeling following spine-specific PMMA injection in an osteoporotic Sprague-Dawley (SD) rat model. Twenty-four osteoporotic female SD rats were randomly assigned to three groups: Control (untreated), OVX + spine-specific PMMA (OVX + PMMA), and OVX (OVX + Defect). Bone regeneration was assessed using dual-energy X-ray absorptiometry (DXA), micro-computed tomography (Micro-CT), quantitative PCR (qPCR), immunohistochemistry (IHC), and Western blotting. At 12 weeks post-injection, the OVX + PMMA group exhibited significantly greater bone regeneration than the OVX group. Micro-CT analysis demonstrated a marked increase in trabecular thickness in the PMMA-treated group. Notably, bone formation was more pronounced in regions surrounding the cement compared to adjacent untreated areas. This suggests that spine-specific PMMA promotes osteogenesis via localized thermal necrosis and subsequent osteoblast recruitment. These findings highlight the dual role of spine-specific PMMA in both structural stabilization and biologically driven bone regeneration. Further research is warranted to optimize its clinical applications while minimizing potential adverse effects.