Liver cell transplantation may provide a means to replace lost or deficient liver tissue, but devices capable of delivering hepatocytes to a desirable anatomic location and guiding the development of a new tissue from these cells and the host tissue are needed. We have investigated whether sponges fabricated from poly-L-lactic acid (PLA) infiltrated with polyvinyl alcohol (PVA) would meet these requirements. Highly porous sponges (porosity = 90-95%) were fabricated from PLA using a particulate leaching technique. To enable even and efficient cell seeding, the devices were infiltrated with the hydrophilic polymer polyvinyl alcohol (PVA). This reduced their contact angle with water from 79 to 23 degrees, but did not inhibit the ability of hepatocytes to adhere to the polymer. Porous sponges of PLA infiltrated with PVA readily absorbed aqueous solutions into 98% of their pore volume, and could be evenly seeded with high densities (5 x 10(7) cells/mL) of hepatocytes. Hepatocyte-seeded devices were implanted into the mesentery of laboratory rats, and 6 +/- 2 x 10(5) of the hepatocytes engrafted per sponge. Fibrovascular tissue invaded through the devices' pores, leading to a composite tissue consisting of hepatocytes, blood vessels and fibrous tissue, and the polymer sponge.
Fibrinogen-related domains (FReDs) are found in a variety of animal proteins with widely different functions, ranging from non-self recognition to clot formation. All appear to have a common surface where binding of one sort or other occurs. An examination of 19 completed animal genomes-including a sponge and sea anemone, six protostomes, and 11 deuterostomeshas allowed phylogenies to be constructed that show where various types of FReP (proteins containing FReDs) first made their appearance. Comparisons of sequences and structures also reveal particular features that correlate with function, including the influence of neighbor-domains. A particular set of insertions in the carboxyl-terminal subdomain was involved in the transition from structures known to bind sugars to those known to bind amino-terminal peptides. Perhaps not unexpectedly, FReDs with different functions have changed at different rates, with ficolins by far the fastest changing group. Significantly, the greatest amount of change in ficolin FReDs occurs in the third subdomain (''P domain''), the very opposite of the situation in most other vertebrate FReDs. The unbalanced style of change was also observed in FReDs from nonchordates, many of which have been implicated in innate immunity.
Tissue engineering (TE) offers a potential solution for the shortage of transplantable organs and the need for novel methods of tissue repair. Methods of TE have advanced significantly in recent years, but there are challenges to using engineered tissues and organs including but not limited to: biocompatibility, immunogenicity, biodegradation, and toxicity. Analysis of biomaterials used as scaffolds may, however, elucidate how TE can be enhanced. Ideally, biomaterials should closely mimic the characteristics of desired organ, their function and their in vivo environments. A review of biomaterials used in TE highlighted natural polymers, synthetic polymers, and decellularized organs as sources of scaffolding. Studies of discarded organs supported that decellularization offers a remedy to reducing waste of donor organs, but does not yet provide an effective solution to organ demand because it has shown varied success in vivo depending on organ complexity and physiological requirements. Review of polymer-based scaffolds revealed that a composite scaffold formed by copolymerization is more effective than single polymer scaffolds because it allows copolymers to offset disadvantages a single polymer may possess. Selection of biomaterials for use in TE is essential for transplant success. There is not, however, a singular biomaterial that is universally optimal.
Polymers of lactic and glycolic acid are attractive candidates to fabricate devides to transplant cells and engineer new tissues. These polymers are biocompatible, and exhibit a wide range of erosion times and mechanical properties. This manuscript describes the fabrication and characterization, in vitro and in vivo, of hollow, tubular devices from porous films of various polymers of this family. Porous films of these polymers were formed using a particulate leaching technique, and sealed around Teflon cylinders to form hollow tubular devices. The erosion rate of devices was controlled by the specific polymer utilized for fabrication, and ranged from months to years. Devices fabricated from a 50/50 copolymer of D,L-lactic acid and glycolic acid were completely eroded by 2 months, while devices fabricated from a homopolymer of L-lactic acid showed little mass loss after 1 year. Erosion times for devices fabricated from the other polymers [poly-(D,L-lactic acid) and a 85/15 copolymer] were between these two extremes. Devices were capable of resisting significant compressional forces (150 raN) in vitro, and the compression resistance was controlled by the polymer utilized to fabricate the devices. The ability of the devices to maintain their structure after implantation into the mesentery or omentum of laboratory rats was also dependent of the specific polymer utilized to fabricate the device. These results indicate that it is possible to fabricate tubular devices for tissue engineering applications that exhibit a wide range of erosion rates and mechanical properties.
These findings demonstrate that the addition of intrapelvic plating may offer distinct advantages in prevention of catastrophic construct failure in situations in which significant lateral to medial force is applied to the greater trochanter such as patient falling.
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