Tissue Engineering Strategies for Skeletal Repair

Abstract

Keywords tissueengineering.bone.cartilage.scaffolds.bioreactorsIntroductionThere is a strong medical need for biological tissue graftsthat could reestablish the structure and function of skeletaltissues lost to congenital abnormalities, trauma, and disease.Both the prosthetic devices and autologous tissue grafts aremost helpful in providing the necessary tissue structure, butthey each have serious limitations [1]. Tissue engineeringoffers potential to grow fully biological substitutes of nativetissues, through the individual and combined use of cells,biomaterial scaffolds, and culture systems [2–5].The Potential of Bioengineered Human TissuesIn its most complex incarnation, tissue engineering involvesthe in vitro generation of living, functional tissue grafts bycultivation of cells on biomaterial scaffolds (designed toserve as a template for tissue formation) in bioreactors(providing environmental control and physical signaling).The design of tissue engineering systems has been guidedby biological principles and the need to provide native-like(biomimetic) environments in order to unlock the fullbiological potential of the cells (Fig. 1). Variations of thisapproach resulted in engineered cartilage, bone, andosteochondral grafts [2–4] for implantation studies inanimal models and eventual translation into clinical use.One recently developed approach enables the in vitrocultivation of living human bone grafts customized to matchthe exact anatomical features of the specific defect, usingthe patient’s own cells (Fig. 2). Importantly, engineeredtissues also find application for in vitro screening of cellsand regulatory factors and construction of disease models[6]. Furthermore, engineering a tissue under controllableconditions brings new insights into the progression of tissuedevelopment and identification of the underlying factorsand mechanisms. This knowledge can then also be used todevelop therapeutic modalities that involve mobilizationand regulation of the host’s cells by bioactive acellularimplants.SummaryBioengineered culture platforms can provide tight environ-mental control and the physiological transport and signal-ing, enabling study of cartilage/bone development,regeneration, and disease under conditions that predict thehuman in vivo context [2–4, 6]. The field of bone andcartilage tissue engineering holds significant potential forproviding clinically relevant tissue grafts for restoring jointfunction. These grafts can be personalized using imaging-guided techniques and the patient’s own cells. As our abilityto grow mechanically functional bone and cartilage graftshas progressed, efforts are focusing at tissue interfaces,vascularization of bone, stratification of cartilage, and“conditioning” of grafts to better tolerate the inflammatoryenvironment of an osteoarthritic joint.