Modified Magnesium Hydroxide Nanoparticles Inhibit the Inflammatory Response to Biodegradable Poly(lactide-co-glycolide) Implants

Abstract

Biodegradable polymers have been extensively used in biomedical applications, ranging from regenerative medicine to medical devices. However, the acidic byproducts resulting from degradation can generate vigorous inflammatory reactions, often leading to clinical failure. We present an approach to prevent acid-induced inflammatory responses associated with biodegradable polymers, here poly(lactide- co-glycolide), by using oligo(lactide)-grafted magnesium hydroxide (Mg(OH)) nanoparticles, which neutralize the acidic environment. In particular, we demonstrated that incorporating the modified Mg(OH) nanoparticles within degradable coatings on drug-eluting arterial stents efficiently attenuates the inflammatory response and in-stent intimal thickening by more than 97 and 60%, respectively, in the porcine coronary artery, compared with that of drug-eluting stent control. We also observed that decreased inflammation allows better reconstruction of mouse renal glomeruli in a kidney tissue regeneration model. Such modified Mg(OH) nanoparticles may be useful to extend the applicability and improve clinical success of biodegradable devices used in various biomedical fields.

Systemic Review of Biodegradable Nanomaterials in Nanomedicine

“…New drug-eluting stents have been developed to not only minimize neointimal hyperplasia and reduce restenosis after revascularization, but also minimize stent thrombosis, a problem that was observed at higher frequency with the first generation stents [114]. Recently, Lih et al developed a new approach to prevent acid-induced inflammatory responses associated with biodegradable PLGA, by neutralizing the acidic environment using oligo(lactide)-grafted magnesium hydroxide (Mg(OH) 2 ) nanoparticles [115]. They demonstrated in porcine models that incorporating the modified Mg(OH) 2 nanoparticles within degradable coatings on drug-eluting arterial stents could efficiently attenuate the inflammatory response and in-stent intimal thickening [115].…”

“…Recently, Lih et al developed a new approach to prevent acid-induced inflammatory responses associated with biodegradable PLGA, by neutralizing the acidic environment using oligo(lactide)-grafted magnesium hydroxide (Mg(OH) 2 ) nanoparticles [115]. They demonstrated in porcine models that incorporating the modified Mg(OH) 2 nanoparticles within degradable coatings on drug-eluting arterial stents could efficiently attenuate the inflammatory response and in-stent intimal thickening [115]. Their results suggested that modifications of biodegradable nanoparticles could be useful to broaden the applicability and improve clinical success of biodegradable devices used in various biomedical fields.…”

Functional Microgels: Recent Advances in Their Biomedical Applications

“…To overcome this, basic additives such as Mg(OH) 2 and Ca(OH) 2 are encapsulated in the PLGA matrix. [65,66] Besides PLGA, significant efforts are being made in the direction of developing degradable microgels based on other polymers in order to facilitate the drug release along with the renal clearance of the final degraded products, leading to reduced toxicity. To explore the potential of microgel particles for biomedical applications, a number of different strategies have been introduced in the chemical design of microgels such as hydrazone-, ketal-, acetal-, disulfide-, carbonate ester-, and siloxane-based crosslinking which can be cleaved by tuning the surrounding medium.…”

Magnesium hydroxide-incorporated PLGA composite attenuates inflammation and promotes BMP2-induced bone formation in spinal fusion

“… 31 , 32 Based on the finding from our previous studies, in this study, we designed a PLGA/MH composite scaffold with pH neutralization and anti-inflammatory properties on the implanting site. 7 , 19 , 32 – 36 Additionally, in order to enhance osteogenic activity, the PLGA/MH composite scaffold surface was coated with polydopamine (PDA) as an adhesive interlayer and BMP2 was sequentially immobilized on the PDA-coated PLGA/MH composite scaffold. After configuring the scaffold, we evaluated in vitro and in vivo osteogenic activity of the BMP2-immobilized PLGA/MH scaffold.…”