Bioengineered titanium implants functionalized with aptamer-valproic acid conjugates orchestrate macrophage...

Area of Science:

• Biomaterials Engineering
• Regenerative Medicine
• Immunomodulation

Background:

• Conventional titanium implants have limited bioactivity and fail to adequately modulate immune responses, leading to poor osseointegration.
• Existing implants struggle to promote endogenous regeneration and optimize the host's response for better bone healing.

Purpose of the Study:

• To develop a multifunctional implant (NTP/Apt-VPA) by conjugating a mesenchymal stem cell (MSC)-specific aptamer (Apt19s) with valproic acid (VPA) on a TiO2 nanotubular surface.
• To evaluate the implant's ability to scavenge reactive oxygen species, modulate macrophage phenotype, and enhance MSC recruitment and osteogenic differentiation.
• To investigate the underlying molecular mechanisms, including osteogenic pathways, involved in improved osseointegration.

Main Methods:

• Conjugation of Apt19s and VPA onto a polydopamine-coated TiO2 nanotubular surface to create the NTP/Apt-VPA implant.
• In vitro and in vivo assessments to evaluate the implant's biological performance.
• RNA sequencing analysis to identify activated osteogenic and signaling pathways.

Main Results:

• The NTP/Apt-VPA implant effectively scavenged reactive oxygen species and programmed macrophages towards a regenerative M2 phenotype.
• Enhanced recruitment and osteogenic differentiation of MSCs were observed with the modified implant.
• Accelerated early inflammation resolution, improved stem cell homing, and activation of PI3K/AKT and MAPK signaling pathways were confirmed.

Conclusions:

• The bioengineering strategy of synchronizing immunomodulation with osteogenesis via an Apt19s-VPA conjugate offers a promising platform for enhancing implant osseointegration.
• The multifunctional implant demonstrates potential for improving bone regeneration and clinical outcomes in orthopedic and dental applications.