Chapter

Poly-4-hydroxybutyrate (P4HB) in Biomedical Applications and Tissue Engineering

If you want to read the PDF, try requesting it from the authors.

Abstract

Poly-4-hydroxybutyrate (P4HB) is a resorbable, thermoplastic homopolyester with a linear chain structure of 4-hydroxybutyrate monomers. High molecular weight P4HB is difficult to synthesize chemically but can be produced via a recombinant bacterial fermentation process through biologic catalysis using enzymes from the polyhydroxyalkanoate biosynthetic pathway. Due to its biocompatibility and biodegradability, as well as its unique mechanical properties, P4HB has emerged during the last decade as a promising biomaterial for various biomedical applications including tissue engineering (congenital heart defects, heart valves and vascular grafts), suture materials, and surgical textiles. In 2007, the TephaFLEX® absorbable monofilament suture was the first medical device derived from P4HB cleared for clinical use by the Food and Drug Administration (FDA) in the United States. Since then, additional regulatory clearances in the US and Europe have expanded the applications of P4HB products to include devices for hernia repair, tendon and ligament repair, and plastic and reconstructive surgery. This chapter will review the unique characteristics of P4HB polymer for use in resorbable medical evices, its processing into various forms, together with strategies that can be used to tailor the material properties for a variety of clinical applications. A number of exciting tissue engineering products based on P4HB that are currently in development, including vascular grafts and heart valves, will be presented as well as examples of potential future medical applications of P4HB in regenerative medicine.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Like, they are elastic, show higher glass transition temperatures, and can incorporate with the myocardial network and conjugates with bioactive molecules (vascular endothelial growth factor) that further escalates cellular attachment, proliferation and viability [110,111]. Recently, P4HB and P3HO have been used as a promising biomaterial in cardiac tissue engineering for rectifying congenital heart defects, vascular grafts and heart valves [112,113]. Another bioplastic i.e. PHBVHHx and PHB4HB have been used in the form of membranes and for the production of cardiac patches respectively [114,115]. ...
Article
Biological polyesters of hydroxyacids are known as polyhydroxyalkanoates (PHA). They have proved to be an alternative, environmentally friendly and attractive candidate for the replacement of petroleum-based plastics in many applications. Many bacteria synthesize these compounds as an intracellular carbon and energy compound usually under unbalanced growth conditions. Biodegradability and biocompatibility of different PHA has been studied in cell culture systems or in an animal host during the last few decades. Such investigations have proposed that PHA can be used as biomaterials for applications in conventional medical devices such as sutures, patches, meshes, implants, and tissue engineering scaffolds as well. Moreover, findings related to encapsulation capability and degradation kinetics of some PHA polymers has paved their way for development of controlled drug delivery systems. The present review discusses about bio-plastics, their characteristics, examines the key findings and recent advances highlighting the usage of bio-plastics in different medical devices. The patents concerning to PHA application in biomedical field have been also enlisted that will provide a brief overview of the status of research in bio-plastic. This would help medical researchers and practitioners to replace the synthetic plastics aids that are currently being used. Simultaneously, it could also prove to be a strong step in reducing the plastic pollution that surged abruptly due to the COVID-19 medical waste.
... Melt-spinning trials have been reported for P3HB (T m~1 80 • C) [107][108][109][110][111][112], PHBV (T m~1 70 • C) [113][114][115] and PHBH (T m~1 45 • C) [116][117][118][119]. In 2007, Tepha (Lexington, KY, USA) launched P4HB (T m~6 0 • C) mono-and multifilaments for medical applications [120,121]. ...
Article
Full-text available
Textiles have a very long history, but they are far from becoming outdated. They gain new importance in technical applications, and man-made fibers are at the center of this ongoing innovation. The development of high-tech textiles relies on enhancements of fiber raw materials and processing techniques. Today, melt spinning of polymers is the most commonly used method for manufacturing commercial fibers, due to the simplicity of the production line, high spinning velocities, low production cost and environmental friendliness. Topics covered in this review are established and novel polymers, additives and processes used in melt spinning. In addition, fundamental questions regarding fiber morphologies, structure-property relationships, as well as flow and draw instabilities are addressed. Multicomponent melt-spinning, where several functionalities can be combined in one fiber, is also discussed. Finally, textile applications and melt-spun fiber specialties are presented, which emphasize how ongoing research efforts keep the high value of fibers and textiles alive.
Article
Nearly all autologous tissue techniques and engineered tissue substitutes utilized for nipple reconstruction are hindered by scar contracture and loss of projection of the reconstructed nipple. The use of unprocessed costal cartilage (CC) as an internal support for the reconstructed nipple has not been widely adopted because of the excessively firm resultant construct. Herein we use a 3D-printed Poly-4-Hydroxybutyrate (P4HB) bioabsorbable scaffold filled with mechanically processed patient-derived CC to foster ingrowth of tissue in vivo to protect the regenerated tissue from contractile forces as it matures. After 6 months in vivo, newly formed spongy fibrovascular cartilaginous tissue was noted in processed CC filled 3D-printed scaffolds, which maintained significantly greater projection than reconstructions without scaffolds. Interestingly, 3D-printed P4HB scaffolds designed with an internal 3D lattice of P4HB filaments (without CC) displayed the fastest material absorption and vascularized adipose-fibrous tissue as demonstrated by SEM and histological analysis, respectively. Using 3D-printed P4HB scaffolds filled with either processed CC, a 3D P4HB lattice or no fills, we have engineered neo-nipples that maintain projection over time, while approximating the biomechanical properties of the native human nipple. We believe that this innovative 3D-printed P4HB nipple reconstruction scaffold will be readily translatable to the clinic. Statement of Significance : Nearly all autologous tissue techniques and engineered tissue substitutes utilized for nipple reconstruction are hindered by scar contracture and substantial loss of projection of the reconstructed nipple, leading to significant patient dissatisfaction. Using 3D-printed P4HB scaffolds filled with either processed costal cartilage or 3D P4HB lattices, we have engineered neo-nipples that resist the forces induced by scar contracture, resulting in maintenance of neo-nipple projection over time and biomechanically approximating human nipples after 6 months in vivo implantation. This novel 3D-printed bioabsorbable P4HB scaffold will be readily translatable to the clinic to reconstruct nipples with patient-specific dimensions and long-lasting projection.
Article
Polyhydroxyalkanoates (PHAs) are sustainable, versatile, biocompatible, and bioresorbable polymers that are suitable for biomedical applications. Produced via bacterial fermentation under nutrient-limiting conditions, they are uncovering a new horizon for devices in biomedical applications. A wide range of cell types including bone, cartilage, nerve, cardiac, and pancreatic cells, readily attach grow and are functional on PHAs. The tuneable physical properties and resorption rates of PHAs provide a toolbox for biomedical engineers in developing devices for hard and soft tissue engineering applications and drug delivery. The versatility of PHAs and the vast range of different PHA-based prototypes are discussed. Current in vitro, ex vivo, and in vivo development work are described and their regulatory approvals are reviewed.
Article
Full-text available
Polyhydroxyalkanoates (PHAs), a family of natural biopolyesters, are widely used in many applications, especially in biomedicine. Since they are produced by a variety of microorganisms, they possess special properties that synthetic polyesters do not have. Their biocompatibility, biodegradability, and non-toxicity are the crucial properties that make these biologically produced thermoplastics and elastomers suitable for their applications as biomaterials. Bacterial or archaeal fermentation by the combination of different carbohydrates or by the addition of specific inductors allows the bioproduction of a great variety of members from the PHAs family with diverse material properties. Poly(3-hydroxybutyrate) (PHB) and its copolymers, such as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHVB) or poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (PHB4HB), are the most frequently used PHAs in the field of biomedicine. PHAs have been used in implantology as sutures and valves, in tissue engineering as bone graft substitutes, cartilage, stents for nerve repair, and cardiovascular patches. Due to their good biodegradability in the body and their breakdown products being unhazardous, they have also been remarkably applied as drug carriers for delivery systems. As lately there has been considerable and growing interest in the use of PHAs as biomaterials and their application in the field of medicine, this review provides an insight into the most recent scientific studies and advances in PHAs exploitation in biomedicine.
Article
Full-text available
The GalaFLEX Scaffold (Galatea Surgical, Inc., Lexington, MA) for plastic and reconstructive surgery belongs to a new generation of products for soft tissue reinforcement made from poly-4-hydroxybutyrate (P4HB). Other members of this new family of products include MonoMax Suture (Aesculap AG, Tuttlingen, Germany) for soft tissue approximation, BioFiber Scaffold (Tornier, Inc., Edina, MN) for tendon repair, and Phasix Mesh (C.R. Bard, Inc., Murray Hill, NJ) for hernia repair. Each of these fully resorbable products provides prolonged strength retention, typically 50% to 70% strength retention at 12 weeks, and facilitates remodeling in vivo to provide a strong, lasting repair. P4HB belongs to a naturally occurring class of biopolymers and fibers made from it are uniquely strong, flexible, and biocompatible. GalaFLEX Scaffold is comprised of high-strength, resorbable P4HB monofilament fibers. It is a knitted macroporous scaffold intended to elevate, reinforce, and repair soft tissue. The scaffold acts as a lattice for new tissue growth, which is rapidly vascularized and becomes fully integrated with adjacent tissue as the fibers resorb. In this review, we describe the development of P4HB, its production, properties, safety, and biocompatibility of devices made from P4HB. Early clinical results and current clinical applications of products made from P4HB are also discussed. The results of post-market clinical studies evaluating the GalaFLEX Scaffold in rhytidectomy and cosmetic breast surgery demonstrate that the scaffold can reinforce lifted soft tissue, resulting in persistent surgical results in the face and neck at one year, and provide lower pole stability after breast lift at one year. © 2016 The American Society for Aesthetic Plastic Surgery, Inc.
ResearchGate has not been able to resolve any references for this publication.