Artificial Polymer Skin with Tunable Properties for Tissue Engineering

Technology #15862

Questions about this technology? Ask a Technology Manager

Download Printable PDF

Image Gallery
In vivo and in vitro evaluation of growth-factor release. PDGF-BB and BMP-2 were loaded into the multilayers that coated the membrane and then implanted in the critical-size defect of a rat calvaria (n = 4 or 5 per group). (A) In vivo release of PDGF-BB and BMP-2 was tracked for 11 and 20 d, respectively. (B) In vitro growth-factor release in single and combination PEM coatings, with release from the first 24 h (Insets). Data represent the means ± SEM. (Shah et al.)μCT imaging of bone repair in live animals. (A) Representative radiographs of bone formation around drilled implants with different coatings at 1, 2, and 4 wk. Red broken circle indicates the location of the defect in each radiograph and has an 8-mm diameter. Defect closure was achieved in all animal groups with different treatment conditions within 4 wk. n = 5 per group. (B) The images in A were used to quantify BV and BMD at 2 and 4 wk within the regions of interest marked by dotted red circles. Each point represents an individual animal. Data are means ± SEM (n = 5 or 6 per group). *P < 0.05; **P < 0.01; ***P < 0.001; ns, not significant (ANOVA with Tukey post hoc test). All groups are compared with the mechanical properties of the M+B0.2+P0.2 group. (Shah et al.)Histology of new tissue formed with various coating formulations. (A) Each image is a cross-section of the calvarial defect after 4 wk, at which time different levels of bone-tissue morphogenesis was observed at the defect site. The broken lines indicate the position of the defect site and are 8 mm apart. Collagen is represented by blue, and osteocytes (mature bone) are represented by red. Sections were stained with Masson’s trichrome stain and viewed under bright-field microscopy. (B) Granulation tissue layer at 1, 2, and 4 wk during bone repair in the M+B0.2+P0.2 treatment group. The tissue gradually reduces in thickness from 1 to 4 wk as bone repair is completed. Pieces of the PLGA membrane were observed in some section. (Scale bars, 30 μm.) Arrowheads: red, PLGA membrane; yellow, granulation tissue layer. (Shah et al.)
Categories
Inventors
Professor Paula Hammond
Department of Chemical Engineering, MIT
External Link (hammondlab.mit.edu)
Nisarg Shah
Department of Chemical Engineering, MIT
Nasim Hyder
Department of Chemical Engineering, MIT
Managed By
Jon Gilbert
MIT Technology Licensing Officer
Patent Protection

Adaptive Drug Delivery from an Artificial Polymer Skin with Tunable Properties for Tissue Engineering

US Patent Pending 2016-0038632
Publications
Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction
PNAS, July 2014

Applications

This invention promotes repair of damaged bone and bone tissue without the need for auto or synthetic grafts for improved defect healing.

Problem Addressed

Bone and bone tissue can only self-regenerate when the damage or defect is small, less than ~8mm. Larger defects require intervention to heal, and conventional treatment options are susceptible to failure due to the low rate of defect closure or the difficulty and/or complexity of the associated surgical procedures. For instance, autograft transplantation, grafting real bone from a patient’s body at a defect site, not only has a limited bone grafting supply, but is also associated with a number of complications including: sever herniation, vascular injury, donor site infection, neurologic injuries, hematoma, iliac fracture, and the need for revision surgery. Alternatively, synthetic materials have been used for grafting but are difficult to integrate with the host bone, often have trouble conforming to a defect, can cause disease such as osteoporosis, and still commonly require revision surgery. This technology allows for rapid repair of large bone and/or tissue defects without complex implant surgery and/or auto graft bone.

Technology

This invention is a composite device, tailored to fit a defect site, which degrades over a period of time while releasing locally, either concurrently or staggered, growth factors to induce and sustain bone regeneration. This technology mimics the natural healing cascade using a porous polymer membrane for controlled bone formation and bone tissue regeneration without fibrous tissue ingrowth in large defects by recapitulating the cellular regenerative process and providing structural support to guide said process. The membrane is composed using poly(lactic-co­glycolic acid) (PLGA) and can be coated conformally with BMP-2, or other growth factors, using the Layber-by-Layer (LbL) approach which allows high loading and prevents exposure of sensitive growth factors to solvents used for membrane formation. The porosity and mechanical and degradation properties of the membrane may be easily manipulated for specific applications. The inventors have already shown multi­week sustained release of growth factor and rapid initiation of the closure of a critical defect, which would have not healed spontaneously, as early as 1 week post-surgery.

Advantages

  • Biocompatible and biodegradable
  • Device may be tailored to specific injury and the degradation, mechanical properties, and porosity may be controlled
  • LbL coating allows high loading and controlled release of one or more growth factors on engineered timescales
  • Prevents fibrous tissue ingrowth
  • Protects growth factors from solvents
  • Localized release reduces risk of unwanted additional biological affects and/or toxicity