Imagine hearing that your newborn, only a few minutes out of womb, has a heart defect and will only live a couple more days. Shockingly, 1 in every 125 babies is born with some type of con-genital heart defect, drastically reducing his or her lifespan.1 However, research institutes and hospitals nationwide are testing solutions and advanced devices to treat this condition. The most promising approach is the defect patch, in which scaffolds of tissue are engineered to mimic a healthy heart. The heart is enormously complex; mimicking is easier said than done. These patches require a tensile strength (for the heart’s pulses and variances) that is greater than that of the left ventricle of the human.1 To add to the difficulty of creating such a device, layers of the patch have to be not only tense and strong, but also soft and supple, as cardiac cells prefer mal-leable tissue environments.
Researchers have taken on this challenge and, through testing various biomaterials, have de-termined the compatibility of each material within the patch. The materials are judged on the ba-sis of their biocompatibility, biodegradable nature, reabsorption, strength, and shapeability.2 Natural possibilities include gelatin, chitosan, fibrin, and submucosa.1 Though gelatin is easily biode-gradable, it has poor strength and lacks cell surface adhesion properties. Similarly, fibrin binds to different receptors, but with weak compression.3 On the artificial side, the polyglycolic acid (PGA) polymer, is strong and porous, while the poly lactic co-glycolic acid (PLGA) polymer has regulated biological properties, but poor cell attachment. This trade-off between different components of a good patch is what makes the building and modification of these systems so difficult. Nevertheless, the future of defect patches is extremely promising.
An unnatural polymer that is often used in creating patches is polycaprolactone, or PCL. This material is covered with gelatin-chitosan hydrogel to form a hydrophilic (water-conducive) patch.1 In the process of making the patch, many different solutions of PCL matrices are pre-pared. The tension of the patch is measured to make sure that it will not rip or become damaged due to increased heart rate as the child develops. The force of the patch must always be greater than that of the left ventricle to ensure that the patch and the heart muscles do not rupture.1 Although many considerations must be accounted for in making this artificial patch, the malleability and adhesive strength of the device are the most important.1 Imagine a 12-year-old child with a defect patch implanted in the heart. Suppose this child attempts to do a cardio workout, including 100 jumping jacks, a few laps around a track, and some pushups. The heart patch must be able to reach the ultimate tensile strain under stress without detaching or bursting. The PCL core of the patch must also be able to handle large bursts of activity. Finally, the patch must be able to grow with the child and the heart must be able to grow new cells around the patch. In summary, the PCL patch must be biodegradable, have sufficient mechanical strength, and remain viable under harsh conditions.
While artificial materials like PCL are effective, in some situations, the aforementioned design criteria are best fulfilled by patches made from natural biomaterials. For instance, chitosan serves as a good template for the outside portion of the patch.4 This material is biocompatible, bioabsorbable, and shapeable. Using natural materials can reduce the risk of vascularization, or the abnormal formation of blood vessels. They can also adapt to gradual changes of the heart. Natural patches being developed and tested in Dr. Jeffrey Jacot’s lab at Rice University include a core of stem cells, which can differentiate into more specialized cells as the heart grows. They currently contain amniotic fluid-derived stem cells (AFSC) which must be isolated from hu-mans.5 Researchers prepare a layer of chitosan (or fibrin in some cases) and polyethylene gly-col hydrogels to compose the outside part of the patch.4 They then inject AFSC into this matrix to form the final patch. The efficiency of the patch is measured by recording the stem cells’ ability to transform into new cells. In experiments, AFSC are able to differentiate into virtually any cell type, and are particularly promising in regenerative medicine.5 These initial prototypes are still being developed and thoroughly tested on rodents.6 A major limitation of this approach is the ina-bility of patches to adapt in rapidly developing hearts, such as those of human infants and patch testing on humans or even larger mammals has yet to be done. The most important challenges for the future of defect patches are flexibility and adaptability.6 After all, this patch is essentially a transformed and repaired body part. Through the work of labs like Dr. Jacot’s, cardiac defects in infants and children may be completely treatable with a patch. Hopefully, in the future, babies with this “Band-Aid” may have more than a few weeks to live, if not an entire lifetime.
References
- Pok, S., et al., ACS Nano. 2014, 9822–9832.
- Pok, S., et al., Acta Biomaterialia. 5630–5642.
- Pok, S., et al., Journal of Cardiovascular Translational Research J. of Cardiovasc. Trans. Res. 2011, 646–654.
- Tottey, S., Johnson, et al. Biomaterials. 2011, 32(1), 128– 136.
- Benavides, O. M., et al., Tissue Engineering Part A. 1185–1194.
- Pok, S., et al., Tissue Engineering Part A. 1877–1887.