Yannas I V, Lee E, Orgill D P, Skrabut E M, Murphy G F
Fibers and Polymers Laboratories, Massachusetts Institute of Technology, Cambridge 02139.
Proc Natl Acad Sci U S A. 1989 Feb;86(3):933-7. doi: 10.1073/pnas.86.3.933.
Regeneration of the dermis does not occur spontaneously in the adult mammal. The epidermis is regenerated spontaneously provided there is a dermal substrate over which it can migrate. Certain highly porous, crosslinked collagen-glycosaminoglycan copolymers have induced partial morphogenesis of skin when seeded with dermal and epidermal cells and then grafted on standard, full-thickness skin wounds in the adult guinea pig. A mature epidermis and a nearly physiological dermis, which lacked hair follicles but was demonstrably different from scar, were regenerated over areas as large as 16 cm2. These chemical analogs of extracellular matrices were morphogenetically active provided that the average pore diameter ranged between 20 and 125 microns, the resistance to degradation by collagenase exceeded a critical limit, and the density of autologous dermal and epidermal cells inoculated therein was greater than 5 x 10(4) cells per cm2 of wound area. Unseeded copolymers with physical structures that were within these limits delayed the onset of wound contraction by about 10 days but did not eventually prevent it. Seeded copolymers not only delayed contraction but eventually arrested and reversed it while new skin was being regenerated. The data identify a model extracellular matrix that acts as if it were an insoluble growth factor with narrowly specified physiochemical structure, functioning as a transient basal lamina during morphogenesis of skin.
在成年哺乳动物中,真皮不会自发再生。只要有真皮基质供其迁移,表皮就能自发再生。某些高度多孔的交联胶原 - 糖胺聚糖共聚物,在接种真皮细胞和表皮细胞后移植到成年豚鼠的标准全层皮肤伤口上时,可诱导皮肤部分形态发生。在面积达16平方厘米的区域上再生出了成熟的表皮和几乎具有生理功能的真皮,该真皮虽没有毛囊,但明显不同于瘢痕。只要平均孔径在20至125微米之间,对胶原酶降解的抵抗力超过临界限度,且接种到其中的自体真皮细胞和表皮细胞密度大于每平方厘米伤口面积5×10⁴个细胞,这些细胞外基质的化学类似物就具有形态发生活性。具有在这些限度内物理结构的未接种共聚物可使伤口收缩的起始延迟约10天,但最终并不能阻止收缩。接种的共聚物不仅延迟收缩,而且在新皮肤再生时最终阻止并逆转了收缩。这些数据确定了一种模型细胞外基质,其作用就好像是一种具有严格特定理化结构的不溶性生长因子,在皮肤形态发生过程中充当临时基底膜。