Table1_The role of smart polymeric biomaterials in bone regeneration: a review.DOCX

Addressing critical bone defects necessitates innovative solutions beyond traditional methods, which are constrained by issues such as immune rejection and donor scarcity. Smart polymeric biomaterials that respond to external stimuli have emerged as a promising alternative, fostering endogenous bone regeneration. Light-responsive polymers, employed in 3D-printed scaffolds and photothermal therapies, enhance antibacterial efficiency and bone repair. Thermo-responsive biomaterials show promise in controlled bioactive agent release, stimulating osteocyte differentiation and bone regeneration. Further, the integration of conductive elements into polymers improves electrical signal transmission, influencing cellular behavior positively. Innovations include advanced 3D-printed poly (l-lactic acid) scaffolds, polyurethane foam scaffolds promoting cell differentiation, and responsive polymeric biomaterials for osteogenic and antibacterial drug delivery. Other developments focus on enzyme-responsive and redox-responsive polymers, which offer potential for bone regeneration and combat infection. Biomaterials responsive to mechanical, magnetic, and acoustic stimuli also show potential in bone regeneration, including mechanically-responsive polymers, magnetic-responsive biomaterials with superparamagnetic iron oxide nanoparticles, and acoustic-responsive biomaterials. In conclusion, smart biopolymers are reshaping scaffold design and bone regeneration strategies. However, understanding their advantages and limitations is vital, indicating the need for continued exploratory research.</p

Differentiation (A, C) and mineralization (B) of bone marrow cells was decreased in P2Y₂ KO mice.

<p>(A) Left: Images of AP staining from bone marrow cell cultures; Right: Bar graph representation of AP quantified by colorimetric conversion of p-nitrophenol phosphate to p-nitrophenol and normalized to total protein. (B). Left: Images of von Kossa staining from bone marrow cell cultures; Right: Bar graph representation of calcium qualification by o-cresolphthalein method in each well. (C). Represented images of 35 cycles of RT-PRC show the osteocalcin mRNA levels in bone marrow cells from both WT and P2Y₂ KO mice (β-actin as controls). (n = 4, *p<0.05) Error bars represent SEM.</p

Response to ATP (A) and oscillatory fluid flow (B) was decreased in P2Y₂ KO mice.

<p>(Left: western blot analysis of ERK1/2 phosphorylation in primary osteoblastic cells. Right: Bar graph representation of ERK1/2 phosphorylation quantified by scanning densitometry normalized to total ERK1/2). (n = 4–6, *p<0.05) Each bar represents SEM.</p

Bone loss in P2Y₂ KO age-matched WT and P2Y₂ KO male mice (8 and 17 weeks of age) were subjected to micro-CT analysis.

<p>(A) Parameters of trabecular bone mass, including bone volume fraction (BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th), trabecular separation (Tb. Sp), and bone mineral density (BMD) were quantified; (B) Parameters of cortical bone quantified included bone volume fraction (BV/TV), total volume (TV), cortical bone thickness (Th), and bone mineral density (BMD). (n = 4–6, *p<0.05, **p<0.01) Error bars represent SEM.</p

Mechanical properties of cortical bone were decreased in P2Y₂ KO mice.

<p>Femurs of age-matched WT and P2Y₂ KO male mice (8 and 17 weeks of age) were subjected to three point bending. Ultimate force and stiffness were recorded. (n = 6–8, *p<0.05) Error bars represent SEM.</p