Abstract: Objective To fabricate a new composite scaffold material as an implant for sustained delivery of rifampicin and
evaluate its performance of sustained drug release and biocompatibility. Methods The composite scaffold material was
prepared by loading poly(lactic-co-glycolic) acid (PLGA) microspheres that encapsulated rifampicin in a biphasic calcium
composite material with a negative surface charge. The in vitro drug release characteristics of the microspheres and the
composite scaffold material were evaluated; the in vivo drug release profile of the composite scaffold material implanted in a
rat muscle pouch was evaluated using high-performance liquid chromatography. The biochemical parameters of the serum
and liver histopathologies of the rats receiving the transplantation were observed to assess the biocompatibility of the
composite scaffold material. Results The encapsulation efficiency and drug loading efficiency of microspheres were (56.05 ±
5.33)% and (29.80±2.88)%, respectively. The cumulative drug release rate of the microspheres in vitro was (94.19±5.4)% at 28
days, as compared with the rate of (82.23±6.28)% of composite scaffold material. The drug-loaded composite scaffold material
showed a good performance of in vivo drug release in rats, and the local drug concentration still reached 16.18±0.35 μg/g at 28
days after implantation. Implantation of the composite scaffold material resulted in transient and reversible liver injury, which
was fully reparred at 28 days after the implantation. Conclusion The composite scaffold material possesses a good sustained
drug release capacity and a good biocompatibility, and can serve as an alternative approach to conventional antituberculous
chemotherapy.