Sustained release of ancillary amounts of testosterone and alendronate from PLGA coated pericard membranes and implants to improve bone healing

Abstract

Testosterone and alendronate have been identified as two bone healing compounds which, when combined, synergistically stimulate bone regeneration. This study describes the development of a novel ultrasonic spray coating for sustained release of ancillary amounts of testosterone and alendronate encapsulated in PLGA 5004A as a carrier. Due to the low amounts of testosterone and alendronate used, sensitive in vitro assays were developed to determine in vitro release. The ultrasonic spray coating technology was optimized for coating titanium screws and pericardial collagen membranes, with the aim to improve osseo-integration and (guided) bone regeneration, respectively, without interfering with their primary mode of action. In vitro release analysis of collagen membranes and screws showed up to 21 days sustained release of the compounds without a burst release. Subsequent preclinical studies in rat and rabbit models indicated that testosterone and alendronate coated membranes and screws significantly improved bone regeneration in vivo. Coated membranes significantly improved the formation of new bone in a critical size calvarial defect model in rats (by 160% compared to controls). Coated screws implanted in rabbit femoral condyles significantly improved bone implant contact (69% vs 54% in controls), bone mineral density (121%) and bone volume (119%) up to 1.3 mm from the implant. Based on the results obtained, we suggest that implants or membranes enabled with local sustained delivery of ancillary amounts of testosterone and alendronate can be a promising system to stimulate local bone regeneration resulting in improved osseo-integration of implants and improved healing of bone defects and fractures.

Testosterone Replacement Therapy in Orthopaedic Surgery

“…The study reported that implanted screws coated with testosterone resulted in a markedly increased bone-implant contact surface area and BMD and produced greater bone volume compared with screws not coated with testosterone. 28 These current studies suggest that testosterone incorporation into implant surfaces may encourage increased osteogenesis; however, they do not attempt to assess the relationship of endogenous testosterone level and bone-implant integration. Future investigations may examine the influence of direct testosterone implant integration and systemic TRT on bone-implant integration and healing.…”

Construction of Local Drug Delivery System on Titanium-Based Implants to Improve Osseointegration

“…Based on this property of bisphosphate drugs, researchers loaded them on the Ti implants. They demonstrated that bisphosphate drugs could inhibit the activity of osteoclasts from stimulating local bone regeneration and improve the osseointegration of Ti implants [ 113 ].…”

Locally Applied Repositioned Hormones for Oral Bone and Periodontal Tissue Engineering: A Narrative Review

“…In humans, testosterone is crucial in the male sexual organs, for example the testes, as well as in the promotion of secondary sexual traits such as increased muscular and bone mass [ 107 ]. PLGA-coated pericardial inserts or membranes combining topical gradual administration of supplementary quantities of testosterone and alendronate may be a viable approach for stimulating in situ osteogenesis, leading to enhanced implant osseo-integration and repair of bone defects and fractures [ 79 ]. In mice, testosterone delivered with a scaffold has similar effects to the Bone Morphologic Protein-2 in enhancing bone regeneration [ 108 ].…”