ABSTRACT
AIM: We aimed to investigate freshly isolated compared with culture-expanded chondrocytes with respect to early regenerative response, cytokine production and cartilage formation in response to four commonly used biomaterials. MATERIALS & METHODS: Chondrocytes were both directly and after expansion to passage 2, incorporated into four biomaterials: Polyactive™, Beriplast®, HyStem® and a type II collagen gel. Early cartilage matrix gene expression, cytokine production and glycosaminoglycan (GAG) and DNA content in response to these biomaterials were evaluated. RESULTS: HyStem induced more GAG production, compared with all other biomaterials (p ≤ 0.001). Nonexpanded cells did not always produce more GAGs than expanded chondrocytes, as this was biomaterial-dependent. Cytokine production and early gene expression were not predictive for final regeneration. CONCLUSION: For chondrocyte-based cartilage treatments, the biomaterial best supporting cartilage matrix production will depend on the chondrocyte differentiation state and cannot be predicted from early gene expression or cytokine profile.
Subject(s)
Biocompatible Materials/pharmacology , Cartilage/physiology , Chondrocytes/cytology , Regeneration/drug effects , Aged , Aged, 80 and over , Cartilage/drug effects , Cell Death/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Chondrocytes/drug effects , Chondrocytes/metabolism , Cytokines/metabolism , Extracellular Matrix/drug effects , Extracellular Matrix/genetics , Gene Expression Regulation/drug effects , Humans , L-Lactate Dehydrogenase/metabolism , Middle Aged , Tissue Scaffolds/chemistryABSTRACT
Regenerative medicine (RM) technologies, such as cell therapy, gene transfer and tissue engineering, are expected to move the field of orthopedics into a new era. Now that more and more attempts are underway to translate preclinical research into clinical studies, it is time to proactively discuss the ethical issues associated with first-in-human applications of RM interventions for musculoskeletal disorders. The design and launch of early clinical trials will be ethically challenging due to the specific features of RM in general, and the application for musculoskeletal disorders specifically. In this paper, we identify three sets of ethical issues that need to be addressed when considering initiating early clinical trials: assessment of risks and benefits; designing a study in terms of outcome measures and comparators; and participant selection. These issues are particularly emphasized in RM research that aims to apply these approaches in an early stage of degenerative musculoskeletal disorders.
