Bedazzled biomaterials: Crystallized drugs prevent implant fibrosis

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Science Translational Medicine  24 Jul 2019:
Vol. 11, Issue 502, eaay3579
DOI: 10.1126/scitranslmed.aay3579


Crystallized anti-inflammatory drug formulations incorporated into biomaterial devices reduce fibrotic response when implanted in animal models.

Implantable medical devices, ranging from pacemakers to cell-encapsulating polymers, can induce a detrimental fibrotic response in recipients, potentially resulting in failure of the device. Current approaches to inhibit fibrotic responses often deliver broad-spectrum anti-inflammatories systemically, which can result in off-target side effects. The ability to deliver anti-inflammatory drugs locally at a device-tissue interface could prolong device function and eliminate side effects by minimizing systemic exposure.

A new study published in Nature Materials reports the use of a range of anti-inflammatory drugs to generate concentrated crystallized drug depots within implanted materials. By crystallizing the drugs, sustained delivery was achieved from a range of implantable materials, including alginate hydrogels for intraperitoneal encapsulated cell transplantation and subcutaneous continuous glucose monitoring implants. Reduced fibrosis against crystallized drug–containing implants was observed up to 1.3 years after implantation in rodents and 6 months in nonhuman primates when compared against unmodified implants.

Although these results are promising, there are some limitations to this strategy. Different materials used to encapsulate the crystallized drugs can complicate drug release rate and delivery. Larger crystals tended to correlate with more sustained release, but inclusion of large crystals could lead to defects in the implant material after drug dissolution, potentially worsening fibrosis after drug depots are exhausted. In addition, it is unclear how concentrated, localized drug delivery could affect device functions that involve sensing, such as glucose monitors or neural implants. Despite these potential limitations, this method of incorporating concentrated drug depots within implant materials ranging from hydrogels to silicone and polyimide coatings demonstrates versatility and offers potential benefit for a range of implantable devices and biomaterial applications.

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