Biodegradable cardiac patch for heart repair and regeneration

Heart failure (HF) is a debilitating condition that has serious implications for individuals affected in terms of expectancy and quality of life. HF can have many causes including hypertension, coronary artery disease and myocardial infarction (heart attack). The improvement in acute myocardial infarction (AMI) survival rate is thought to be one of the major factors contributing in the dramatic increase in HF cases seen in recent years. Adult cardiomyocytes have a limited capacity to regenerate; the lost myocytes are normally replaced by fibroblasts and myofibroblasts which form scar tissues. The formation of this non‐contracting fibrous scar alters the workload of the remaining myocardium resulting in remodelling of the heart, leading ultimately to congestive HF. Regeneration of the myocardium is therefore essential for the recovery and survival of patients.

Figure 1. The cardiac patch concept is based on a 3 layer construct:

  1. Stitch resistance PU membrane
  2. Porous natural polymer scaffold
  3. Cell compatible hydrogel

 

 

IN VITRO EVALUATION:

  • A resilient biocompatible biodegradable material

 Thickness (μm)Maximum charge (N)Young Modulus (N/mm2)Load at Break (N)Elongation at break (%)Tensile Stength at Break (mm)Breaking Strain (N/mm2)
PCL composite9784.92481.814.9249.8121.9622.533
PU:PCL composite system15288.41830.9988.47873.58914.7182.793

Figure 2: The device was characterised accordingly to the ISO 10993; (Top Left) Cytotoxicity assessment; (Top Right) Swelling ratio in PBS; (Bottom) Mechanical properties

  • A functionalisable  platform for drugs and cell delivery

Figure 3: The cardiac patch is a technological platform for cell and drug delivery. (Top) In-vivo studies demonstrated the Cardiac Patch as cell carrier for lesion repopulation. rCPC were seeded in-vitro onto the Cardiac Patch. In-vivo, cell migrate from the device to the lesion.

The device can also be functionalised with drug delivery systems. (Bottom), rCPC viability on bare cardiac patchs (blue and black traces), on nanofiber and hydrogel functionalisation for the control release of BMP and HGF growth factors.

IN VIVO DEVICE ASSESSMENT

  • Suturability studies

Figure 4: The cardiac patch was implanted onto the large bowel of pig animal model to test device suturability and haemocompatibilty for a 3 month period of time.

  • Capacity of the device to withstand large blood pressure variations

Figure 5: (Left) The cardiac patch was also implanted on a Sheep aorta to test the devices capacity to withstand large bold pressure variation. (Centre and Right) After 6 months: no aneurysm, thrombosis, fibrosis or inflammation are present at the side and in the vicinity of the implants. Endothelial layers are covering the implants.

  • Device Function

Figure 6: The unfunctionalised device was implanted in LV of rat hearts (Left). After 30 days of implantation, 50% of the LV chamber volume was documented (Right).

CONCLUSION

The Cardiac patch is a 3 component system providing primarily mechanical support to infarcted myocardium to prevent isochemical pathological cascade. The biocompatible and biodegradable device can be functionalised with an ancillary function to allow in-vitro cell seeding and in-vivo cell delivery. The device has been characterised in large animals for its suturability, heamocompatibility, non-thrombogenic and immunogenic properties on various assesment models. Ultimately the unfunctionalised device meets its design requirement by preventing LV tissue remodelling post infact.

 

 

Authors: Constantin Ciobanu(1); Evzen Amler(2); Alberto Saiani(3); Federico Quaini(4); Serghei Cebotari(5);  Guillaume Saint-Pierre(6)

(1) Petru Poni Institute, Romania; (2) Charles Darwin University of Prague, Czech Republic; (3)School of Materials & Manchester Institute for Biotechnology , University of Manchester, UK; (4) University-Hospital of Parma, Italy; (5) Hannover Medical School, Germany; (6) Inspiralia, Spain; 

Acknowledgments: The authors gratefully acknowledge the European Union FP7 Framework Programme Bioscent (Grant no: 214539) and UK Engineering and Physical Sciences Research Council for funding this research (Grant no: EP/K016210/1)