Treating soft tissue via controlled drug release
Inventors
Gottardi, Riccardo • Alexander, Peter • Bianconi, Patrick A. • Little, Steven R.
Assignees
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Publication Number
US-11318103-B2
Publication Date
2022-05-03
Expiration Date
Abstract
Methods for inhibiting tissue ossification or calcification in a subject, comprising administering a therapeutically effective amount of BMP I inhibitor-loaded microparticles to a subject in need thereof, wherein the administration provides local and sustained release of the BMP I inhibitor thereby inhibiting tissue ossification or calcification.
Core Innovation
The invention provides a therapeutic scaffold comprising BMP I inhibitor-loaded microparticles and chondrocytes. The microparticles are configured to deliver a BMP I receptor inhibitor in a local sustained-release form with localized delivery to address undesirable calcification after repair.
The disclosed BMP I inhibitor includes dorsomorphin, and the scaffold is directed toward preventing chondrocyte terminal differentiation and chondrocyte hypertrophy-associated calcification. The document describes use of BMP I inhibition to prevent ossification and calcification in soft tissue and to address osteochondral calcification, calcified cartilage, osteophytes, and heterotopic ossification.
The scaffold and microparticles include bioerodible polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and poly(lactic-co-glycolic acid) (PLGA). The document also describes pharmaceutical compositions associated with BMP I inhibitor-loaded microparticles and chondrocyte components.
Claims Coverage
The independent claim set centers on one therapeutic scaffold combining BMP I inhibitor-loaded microparticles and chondrocytes. Dependent claim features further specify dorsomorphin, microparticle size and polymer composition, and scaffold form or placement, including a surface arrangement and stent or shunt form.
Therapeutic scaffold with BMP I inhibitor-loaded microparticles and chondrocytes
A therapeutic scaffold comprising BMP I inhibitor-loaded microparticles and chondrocytes.
Surface location of microparticles and chondrocytes
The BMP I inhibitor-loaded microparticles and the chondrocytes are located on a surface of the scaffold.
Microparticle volume-average diameter range
The scaffold includes loaded microparticles having a volume-average diameter of 5 to 20 μm.
Dorsomorphin as the BMP I inhibitor
The scaffold is configured such that the inhibitor is dorsomorphin.
Microparticle polymer composition
The microparticles are made of poly glycolide, poly lactic acid, poly(lactic-co-glycolic acid), or a combination thereof.
Scaffold form as stent or shunt
The scaffold is specified to be either a stent or a shunt.
The claim coverage centers on the combination of BMP I inhibitor-loaded microparticles and chondrocytes, further narrowed by dorsomorphin, microparticle material and size constraints, surface placement, and scaffold form.
Stated Advantages
Prevents or reduces cartilage calcification and heterotopic ossification after repair procedures.
Prevents ossification and calcification in soft tissue.
Provides local, sustained delivery of the BMP I inhibitor using BMP I inhibitor-loaded microparticles.
Reduces osteogenesis or ectopic bone formation compared with soluble BMP I inhibitor.
Documented Applications
Knee cartilage repair, including prevention of traumatic or repair-associated cartilage calcification and heterotopic ossification.
Traumatic brain injury heterotopic ossification.
Treating soft tissue to prevent ossification and calcification using BMP I inhibitor-loaded microparticles with chondrocytes.
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