Overview on Biocompatibilities of Implantable Biomaterials - Advances in Biomaterials Science and Biomedical Applications - page 115

for closure of graft and extraction sites, and to promote healing [12]. During in vivo implan‐
tation, collagen irritates slight inflammation accompanying with some scar tissues.

A collagen sponge obtained from Beijing Yierkang Biengineering Development Center Chi‐
na was implanted subcutaneously in rats for time periods up to 8 weeks (Figure 2) [13]. One
week after implantation, slight inflammation with some lymphocytes, myofibrils and fibro‐
blasts were observed. The appearance of myofibrils and fibroblasts indicated that scar tissue
was developed (Figure 2A). Two weeks after implantation, fibrous tissue was formed with
scattered macrophage and lymphocyte cells in the fibrous layer. Newly formed blood ves‐
sels appeared in the implant site while the collagen sponges were completely resorbed (Fig‐
ure 2B). Four weeks after implantation, the thin fiber layer had changed into wavelike scar
tissue and tightly connected with the surrounding muscles. Capillaries were evident in the
new fibrous scars (Figure 2C). Six weeks after implantation, scar tissue in the collagen sam‐
ples was mature (Figure 2D). Eight weeks after implantation, the wave-like scar tissue in the
collagen samples became thinner with some lipocytes and vacuoles (Figure 2E) [13].

Collagen compounds, such as collagen/chitosan, collagen/hyaluronan, have been investigat‐
ed extensively during the past several decades. The biocompatibilities of these compounds
depend largely on the incorporated constituents. For example, a corneal collagen cross-
linked with riboflavin and ultraviolet radiation-A has been used for keratoconus repair of a
29-year-old woman with some good results [14]. In some instances, it is more competing to
use a compound to improve the mechanical properties of the collagen based biomaterials.
For example, a porous implantable dexamethasone-loaded polylactide-co-glycolide (PLGA)
microspheres/collagen glucose sensors [15] and a mitomycin C (MMC) delivery system
(MMC-film), incorporating polylactide (PLA)-MMC nanoparticles in a composite film from
blends of collagen-chitosan-soybean phosphatidylcholine (SPC) with a mass ratio of 4:1:1
have been explored with no sign of internal infection and fibrous encapsulation in any ani‐
mals after 20 days of implantation [16].

Gelatin is a mixture of peptides/proteins produced by partial hydrolysis of collagen extract‐
ed from the skin, boiled crushed bones, connective tissues, organs and some intestines of an‐
imals such as domesticated cattle, chicken, horses hooves, and pigs [17]. Gelatin possesses a
better biocompatibility than its ancestry collagen. Alloimplants of bone matrix gelatin are ef‐
fective in the treatment of bone defects with a low risk of complication such as rejection or
infection [18]. Aqueous gelatin solution is an amorphous natural hydrogel in which cells can
be encapsulated, extruded and deposited at desired positions. Unlike collagen hydrogel, gel‐
atin hydrogel holds a special gelation property around 20℃. In Tsinghua University the au‐
thor's own group, this property has been explored extensively for rapid prototyping (RP)
(or additive manufacturing) of three-dimensional (3D) complex geometrical structures with
computer-aided design channel models [19-24]. Until now, a hybrid hierarchical 3D con‐
struct consisting both synthetic polyurethane PU and natural cell/ gelatin-based hydrogel
with interconnected macro-channels has been produced via a double nozzle RP technique at
a low temperature (-28℃). These constructs have demonstrated excellent in vivo biocompa‐
tibilities [23,25]. This technique holds the potential to be widely used in the future complex
tissue/organ manufacturing areas.