Self-Setting Calcium Orthophosphate Formulations: Cements, Concretes, Pastes, and Putties - Calcium Orthophosphates: Applications in Nature, Biology and Medicine - page 490

and arginine whereas osteogenic differentiation remained unaffected.
Besides, the cement modifications with arginine and aspartic acid,
but not with cocarboxylase, led to a higher BMP-2 binding [295].

Porosity is a very important property to provide good in vivo

bioresorption of implanted biomaterials. Thus, various air-entraining
agents and porogens are commonly used to induce macroporosity
inside calcium orthophosphate cements without affecting their normal
setting. For example, crystals of mannitol, CH OH,

were tested as an air-entraining agent; however, both loss of
workability during the cement mixing and severe depreciation of
mechanical properties were discovered simultaneously [296-301].
Other porogenic agents (e.g.

OH(CHOH) CH

2 4 2

oxygen peroxide [302] in the liquid
phase and/or iced [303], sucrose granules, NaHCO

,

and Na HPO

3 2 4

crystals of 125-250 µm in size [304], poly(D,L-lactic- -glycolic

acid) microparticles with the average size of 66 ± 25 µm [305-310],
pectin microspheres [311], calcium sulfate [46], calcite [219], NaCl
crystals varying in size from 420 μm to 1 mm [312, 313], gelatin
microspheres [314, 315], vesicants [316], cetyltrimethyl ammonium
bromide [317], polytrimethylene carbonate [318], some immiscible
liquids) have been also tested to create porosity. These additives
could be applied on pre-set cements only, while the solubility
degree of the particulates during the setting reaction influences
both the content and dimensions of the macroporosity. After cement
hardening, dissolution of the remaining soluble porogens in either
water or body fluids produces macropores with the dimensions
and shapes of the dissolved crystals. One important limitation
that can be envisaged from this route is the need to add a large
amount of porogenic agent to guarantee interconnectivity of the
porosity, thus compromising not only the excellent biocompatibility
and bioactivity of calcium orthophosphate cements but also the
cements' injectability. Another shortcoming is the lack of strength
of the resulting material, especially if particulates dissolve quickly,
greatly limiting its applications. An innovative approach that aims at
overcoming the lack of interconnectivity and initial strength consists
in using resorbable fibers [319-326]. These fibers have the function
of reinforcing the cement, providing the needed short-term strength
and toughness, and gradually dissolving afterwards, leaving behind

co