**11. Polycaprolactone (PCL)**

sponses to the chitosan systems as stated above can complicate their applications to some degree. The composite chitosan-collagen-soybean phosphatidylcholine film impregnated with MMC-PLA-nanoparticles for treatment of hepatocellular carcinoma in mice has exhib‐ ited some special characteristics compared with pure chitosan delivery systems. In vivo, the growth of the tumors were inhibited considerably and dose-dependently by the MMC-film (P<0.05) with no any signs of vice reactions, such as inflammation, infection, and fibrous en‐ capsulation after 20d of implantation [16,146,147]. Thus a careful balance between the im‐ mune reaction and drug effectiveness is needed when a chitosan pertaining template is used

**10. Polyglycolide (PGA), Polylactide (PLA) and poly(Lactic-co-Glycolic**

Polyglycolide also named polyglycolic acid (PGA) is a biodegradable, thermoplastic poly‐ mer and the simplest linear, aliphatic polyester which contains the ester functional group in it's main chain [148]. It can be prepared starting from glycolic acid by means of polyconden‐ sation or ring-opening polymerization. PGA has been known since 1954 as a tough fiberforming polymer. Owing to its hydrolytic instability, its use has initially been limited [149]. *In vivo*, PGA initiates a marked host reaction around the implantations. This leads to the de‐ velopment of a foreign body response that comprises an initial acute inflammatory phase and a subsequent chronic inflammatory phase. For example, when a synthetic PGA scaffold seeding with adult-derived or somatic lung progenitor cells from mammalian lung tissue was implanted in an immunocompetent host, a serious foreign body response totally altered

Polylactic acid or polylactide (PLA) is another thermoplastic aliphatic polyester derived from renewable resources, such as corn starch, tapioca products, and sugarcanes [30]. A poly(L-lactide) (PLLA) coil stent has ever been implanted in pigs with no stent thrombosis and late restenosis [151]. However, PLA, as well as PLLA, and poly(D,L-lactide) (PDLA), in‐ duces a strong inflammatory response when they are implanted in the body due to their acidic products [152]. Aframian and coworkers implanted tubular PLLA, PGA coated with PLLA (PGA/PLLA), or nothing (sham-operated controls) in Balb/c mice either beneath the skin on the back, and found that inflammatory reactions were shorter and without epithe‐ lioid and giant cells in the sham-operated controls. Tissue responses to PLLA and PGA/ PLLA scaffolds are generally similar in areas subjacent to skin in the back and oral cavity. Biodegradation proceeded more slowly with the PLLA tubules than with the PGA/PLLA tu‐ bules. No significant changes in clinical chemistry and hematology were seen due to the im‐ plantation of tubular scaffolds. [153]. It was reported that, after the PLLA segments were swallowed *in vivo* by phagocytes, cell damage and cell death were obvious. The highest numbers of necrotic cells were observed on day 2 [154]. These reactions can result in an un‐ expected risk for patients and have strongly limited in clinical applications of this kind of

for biomedical applications.

128 Advances in Biomaterials Science and Biomedical Applications

the integrity of the developing lung tissue [150].

**Acid) (PLGA)**

biomaterials.

Polycaprolactone (PCL) is a biodegradable polyester with a low melting point of around 60°C and a glass transition temperature of about −60°C. It is commonly used as an additive for resins or starch to improve their processing characteristics, lower their costs, and change their properties (e.g. impact resistance), or as a plasticizer in the manufacture of special pol‐ ymers (e.g. Pus) [30]. PCL has been approved by the FDA for specific applications, such as a drug delivery devices, sutures, or adhesion barriers. It has been widely used as a scaffold material for tissue engineering with mismatched mechanical properties and slow degrada‐ tion rate [171,172]. In rats the *in vivo* degradation of PCL is about 3 years [173].

Various categories of drugs have been encapsulated in PCL, in microsphere, nanosphere or bulk states, for targeted drug delivery and for controlled drug release [174-176]. For exam‐ ple, a PCL scaffold modified by grafting nerve growth factor (NGF) and Tirofiban (TF) has been used as nerve conduits to promote the regeneration of sciatic nerves [177]. Low molec‐ ular weight PCL pieces can be ingested and digested ultimately by phagocyte and giant cell without any cumulate vice-products (Figure 8) [178-180].

**Figure 8.** Micrographs illustrating extracellular degradation of biomaterials by macrophage fused multinuclear giant cells. (A) A foreign body giant cell (FBGC) engulfed a fragment of poly(epsilon-caprolactone), PCL polymer *in vivo*. Nu, nuclei of FBGC. The PCL polymer was dissolved during sample preparation. Transmission electron microscopy (TEM), bar = 2 μm. (B) *In situ* cross-section of the interface between a multinuclear giant cell (MnGC) and PLGA film. Note the pseudopodia of the MnGC penetrated deep inside the surface of PLGA film and formed sealed compartments. PLGA polymers are eroded within the compartments. Focused ion beam (FIB) microscopy, bar = 5 μm. (C) *In situ* cross-sec‐ tion of the interface between an osteoclasts-like cell (OC) and calcium phosphate cement. Note the typical ruffled board of OC and vesicles (V) secreting from OC to the sealed extracellular space. FIB microscopy, bar = 2 μm [162].
