Regulatory Issues: Down to the Bare Bones - Engineered Bone: Tissue Engineering Intelligence Unit - page 205

C HAPTER 15

Regulatory Issues:
Down to the Bare Bones

Paolo Giannoni and Ranieri Cancedda

Abstract

In this chapter we propose a brief description of the relevant issues that tissue-engineering

researchers must consider when planning new therapeutic approaches, especially in the
bone and cartilage repair field. An overview of the current regulatory authorities is pre-
sented to evidence their role as responsible rule-makers. The influence of the market and of the
private enterprises, as well as that of the academic world, is also taken into consideration when
defining rules to follow.
We will discuss existing guidelines and legislation, giving an overview of the requirements
to be considered when projecting a possible product application in the field of tissue engineer-
ing. The reader's attention will be primarily focused on the cell-based composites, being these
products the most challenging in terms of application of this approach to bone repair. A gen-
eral outlook of the requisites for the manufacturing of tissue-engineered products will be dis-
cussed, spanning from the origin of the cellular component of the composite to the release
criteria of the final product.
The nature of the products or of the therapeutic strategies will not be dealt with, unless they
represent useful examples to evidence the related regulatory issues.

Introduction
Progress in cell biology and biotechnology and improvements in therapeutic treat-
ments have made available to clinicians tissues to be used in reconstructive surgery for the
repair of extensive lesions. In particular, a role for several growth factors controlling cell
proliferation and differentiation has been established and cell culture techniques have
been improved to allow the in vitro selective expansion of restricted cell populations.
Tissue engineering, i.e., the association of ex vivo grown cells and/or biologically active
molecules with different materials, is furthermore driving the production, the testing and
the marketing of new generations of transplantable biomaterials. These can now be used
in unlimited quantities. Ideally the new approaches based on cell-biomaterial associated
products will substitute the previously used devices which do not represent sufficient or
satisfactory solutions. Repair of soft tissues—previously hardly feasible—may now be en-
visioned and performed by transplanting the engineered tissue obtained from the expan-
sion of cells of the patient in association with resorbable materials (either synthetic or of
natural origin).
The first “manipulated” cells intended for structural repair or reconstruction were autolo-
gous keratinocytes expanded ex vivo for treatment of burn wounds and leg ulcers. Additional
examples were chondrocytes cultured and implanted in focal cartilage defects, allogeneic der-
mal fibroblasts for dermal wound healing and the transplant of specific endocrine cells. Other
applications of the tissue engineering approaches presently at a preclinical or very early clinical