Failure of tissues and organs resulting from degenerative diseases or trauma has caused huge economic and health concerns around the world. Tissue engineering represents the only possibility to revert this scenario owing to its potential to regenerate or replace damaged tissues and organs. In a regeneration strategy, biomaterials play a key role promoting new tissue formation by providing adequate space for cell accommodation and appropriate biochemical and biophysical cues to support cell proliferation and differentiation. Among other physical cues, the architectural features of the biomaterial as a kind of instructive stimuli can influence cellular behaviors and guide cells towards a specific tissue organization. Thus, the optimization of biomaterial micro/nano architecture, through different manufacturing techniques, is a crucial strategy for a successful regenerative therapy. Over the last decades, many micro/nanostructured biomaterials have been developed to mimic the defined structure of ECM of various soft and hard tissues. This review intends to provide an overview of the relevant studies on micro/nanostructured scaffolds created for soft and hard tissue regeneration and highlights their biological effects, with a particular focus on striated muscle, cartilage, and bone tissue engineering applications.

Effective clinical treatments for volumetric muscle loss resulting from traumatic injury or resection of a large amount of muscle mass are not available to date. Tissue engineering may represent an alternative treatment approach. Decellularization of tissues and whole organs is a recently introduced platform technology for creating scaffolding materials for tissue engineering and regenerative medicine. The muscle stem cell niche is composed of a three-dimensional architecture of fibrous proteins, proteoglycans and glycosaminoglycans, synthesized by the resident cells that form an intricate extracellular matrix (ECM) network in equilibrium with the surrounding cells and growth factors. A consistent body of evidence indicates that ECM proteins regulate stem cell differentiation and renewal and are highly relevant to tissue engineering applications. The ECM also provides a supportive medium for blood or lymphatic vessels and for nerves. Thus, the ECM is the nature’s ideal biological scaffold material. ECM-based bioscaffolds can be recellularized to create potentially functional constructs as a regenerative medicine strategy for organ replacement or tissue repopulation. This article reviews current strategies for the repair of damaged muscle using bioscaffolds obtained from animal ECM by decellularization of small intestinal submucosa (SIS), urinary bladder mucosa (UB) and skeletal muscle, and proposes some innovative approaches for the application of such strategies in the clinical setting.

Intestinal metaplasia identifies Barrett's esophagus (BE) and is associated with an increased risk for esophageal adenocarcinoma. Dysplasia occurs as an intermediate step. However, progression from metaplasia to neoplasia without the demonstration of dysplasia has been described. The role of dual-parameter flow cytometry (FC) as a predictor of neoplastic risk in dysplasia-free cases was evaluated. DNA/protein FC and histology were performed on 362 samples from 30 dysplasia-free BE patients, followed up since 1985 once every 1–2 years. Nine cases were aneuploid, five of which (group IV) were frankly aneuploid; in the other four cases (group III), aneuploidy was detectable by dual-parameter analysis only. Twenty-one patients were diploid. Twelve (group II) also had an abnormally high G₁-phase protein content compared to group I (nine patients), which were diploid with a low-moderate protein content. In three patients of group IV an adenocarcinoma in situ was diagnosed, after 5, 6, and 10 years, respectively. In two patients of group III, a low- and a high-grade dysplasia were observed at 3 and 6 years follow-up, respectively. One patient of group I first acquired a high protein content, then an aneuploid DNA content, and then progressed to adenocarcinoma (12 years). None of the still diploid patients (17 cases) have progressed to dysplasia or cancer compared with 6 of 13 presently aneuploid patients (P < 0.01). In conclusion, DNA/protein FC is a marker of increased malignant potential and thus may be used to detect patients at higher risk in dysplasia-free BE and assist in understanding the various stages of malignant transformation in long-term follow-up studies. Cytometry (Comm. Clin. Cytometry) 34:257–263, 1998.