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The bone is a complex and dynamic structure subjected to constant stress and remodeling. Due to the worldwide incidence of bone disorders, engineered bone tissues have emerged as solution for bone grafting, which require sophisticated scaffolding architectures while keeping high mechanical performance. However, the conjugation of bone-like scaffold architecture with efficient mechanical properties is still a critical challenge for biomedical applications.  In this sense, the present study is focused on the development of silk fibroin (SF) scaffolds crosslinked with horseradish peroxidase and mixed with zinc (Zn) and strontium (Sr)-doped β-tricalcium phosphate (ZnSr.TCP) to mimic bone structures. The ZnSr.TCP-SF hydrogels were tuned in programmable ice-templating parameters, and further freeze-dried, to obtain 3D scaffolds with controlled pore orientation. The results showed interconnected channels in the ZnSr.TCP-SF scaffolds that mimic the porous network of the native subchondral bone. The architecture of the scaffolds was characterized by microCT and showing tunable pore size according to freezing temperatures (-196 ºC: ~80.2 ± 20.5 µm; -80 ºC: ~73.1 ± 20.5 µm; -20 ºC: ~104.7 ± 33.7 µm). The swelling ratio, weight loss, and rheological properties were also assessed, revealing that the scaffolds were able to keep their integrity and morphology after aqueous immersion. Thus, the ZnSr.TCP-SF scaffolds made of aligned porous structure were developed as affordable candidates for future applications in clinical osteoregeneration and in vitro bone tissue modelling., FCT for the financial support of the Hierarchitech project (M435 ERA.NET/0001/2014) and for the distinctions attributed to S.P. (CEECIND/03673/2017) and C. 436 G. (SFRH/BPD/94277/2013). R. F. Canadas is also thankful to FCT for the doctoral scholarship 437 (SFRH/BD/92565/2013), Fundo Europeu de Desenvolvimento Regional (FEDER), and Programa 438 Operacional Competitividade e Internacionalização (POCI) for funding the Young Researcher 439 Contract (B-Liver Project, PTDC/EMD-EMD/29139/2017)

Osteoarthritis is a degenerative joint disease characterized by the progressive deterioration of articular cartilage, synovial inflammation and changes in periarticular and subchondral bone, being a leading cause of disability. Conventional treatments present several side effects and can involve the use of painkillers and non-steroidal anti-inflammatory drugs. In this sense, researchers have shifted the focus of new therapeutics to biomolecular agents and/or their combination with cells. However, the efficacy of these molecules is dependent on their metabolization which can differ according to the administration route and delivery approach. Consequently, tissue engineering strategy comprising the use of biomaterials can provide support for neo-tissue osteochondral repair/regeneration whilst conferring proper mechanical and functional features as well as protecting biomolecular agents from premature degradation. The current strategies and challenges used in biomaterials functionalization with peptides that can mimic ECM proteins or other natural soluble biomolecules, important to induce the complex interactions between cells and the ECM, are discussed herein. Many opportunities for treating OA are being explored by means of peptide-biofunctionalization of biomaterials which can be designed to be recognizable, induce differentiation, prevent infection, degrade at an intended rate or act as drug delivery systems for controlled release or even as simple triggers of cell behavior., The authors would like to acknowledge the financial supports from the Portuguese Foundation for Science and Technology for the M-ERA.NET/0001/2014 project and for the funds provided under the program Investigador FCT 2012 and 2015 (IF/00423/ 2012 and IF/01285/2015), and European Commission via H2020- MSCA-RISHE programme (BAMOS, Grant No. 734156).

A Kefiran-based scaffold was developed using a freeze gelation technique, and its potential use for both drug delivery system and tissue engineering applications were investigated. This scaffold showed, through micro-computed tomography and scanning electron microscopy, high porosity (82.3 ± 4.4%), thick pore walls (13.4 ± 0.7 μm), aerogel form with foam-like structure, and elastic behaviour (δ = 16 ± 0.7°). Moreover, the Kefiran scaffold degradation showed a delayed profile for over 28 days. The developed scaffold allowed a slow and sustained diclofenac release over two weeks, and the human Adipose-derived Stem Cells, cultured onto the Kefiran scaffold, were metabolically active after 72 h. Therefore, our research suggests that Kefiran cryogel could be a potential candidate for drug delivery of controlled bioactive molecules and tissue engineering scaffolding., Hajer Radhouani, Cristiana Gonçalves and F. Raquel Maia were supported by the Fundação para a ciência e a Tecnologia (FCT) from Portugal, with references CEECIND/00111/2017, SFRH/BPD/94277/2013 and SFRH/BPD/117492/2016, respectively. Diana Bicho was supported through the M-ERA-NET/0001/2014 project (FCT). Joaquim. M. Oliveira would like to thank the FCT for the fund provided under the program Investigador FCT 2015 (IF/01285/2015). This work was funded by the R&D Project KOAT – Kefiran exopolysaccharide: Promising biopolymer for use in regenerative medicine and tissue engineering, with reference PTDC/BTMMAT/29760/2017 (POCI-01-0145-FEDER-029760), financed by FCT and co-financed by European Regional Development Fund (FEDER) and Operational Programme for Competitiveness and Internationalisation (POCI).

The osteochondral tissue represents a complex structure composed of four interconnected structures, namely hyaline cartilage, a thin layer of calcified cartilage, subchondral bone, and cancellous bone. Due to the several difficulties associated with its repair and regeneration, researchers have developed several studies aiming to restore the native tissue, some of which had led to tissue-engineered commercial products. In this sense, this chapter discusses the good manufacturing practices, regulatory medical conditions and challenges on clinical translations that should be fulfilled regarding the safety and efficacy of the new commercialized products. Furthermore, we review the current osteochondral products that are currently being marketed and applied in the clinical setting, emphasizing the advantages and difficulties of each one.