2022 Issue 2 (Available Online: 2022-06-28)

    Ricardo Donate, Maryam Tamaddon, Viviana Ribeiro, Mario Monzón, J. Miguel Oliveira, Chaozong Liu
    2022, 3(2):  102-104.  doi:10.12336/biomatertransl.2022.02.003
    The main results of the in vivo evaluations carried out in Biomaterials and Additive Manufacturing: OsteochondralScaffold (BAMOS) project, funded under Horizon 2020 Research and Innovation Staff Exchanges (RISE) program, are summarized. Animal models of osteochondral defect have been used to assess the biological performance of the different multi-material and multi-layered scaffolds developed.
    Abstract ( 231 )   HTML ( 32)   PDF (239KB) ( 389 )  
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    Osteoarthritis is the most common chronic degenerative joint disease, recognized by the World Health Organization as a public health problem that affects millions of people worldwide. The project Biomaterials and Additive Manufacturing: Osteochondral Scaffold (BAMOS) innovation applied to osteoarthritis, funded under the frame of the Horizon 2020 Research and Innovation Staff Exchanges (RISE) program, aims to delay or avoid the use of joint replacements by developing novel cost-effective osteochondral scaffold technology for early intervention of osteoarthritis. The multidisciplinary consortium of BAMOS, formed by international leading research centres, collaborates through research and innovation staff exchanges. The project covers all the stages of the development before the clinical trials: design of scaffolds, biomaterials development, processability under additive manufacturing, in vitro test, and in vivo test. This paper reports the translational practice adopted in the project in in vivo assessment of the osteochondral scaffolds developed.

    Melika Sahranavard, Soulmaz Sarkari, SeyedehMina Safavi, Farnaz Ghorbani
    2022, 3(2):  105-115.  doi:10.12336/biomatertransl.2022.02.004
    Decellularized extracellular matrix (dECM) can be used as a potential bio-ink for cartilage tissue engineering. This bioink can provide natural cues for cell adhesion and tissue regeneration. Here, the properties, sources, preparation process of dECM bio-inks, and previous studies on dECM bio-ink bio-printing for cartilage regeneration were reviewed.
    Abstract ( 520 )   HTML ( 44)   PDF (1305KB) ( 908 )  
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    Cartilage injuries are common problems that increase with the population aging. Cartilage is an avascular tissue with a relatively low level of cellular mitotic activity, which makes it impossible to heal spontaneously. To compensate for this problem, three-dimensional bio-printing has attracted a great deal of attention in cartilage tissue engineering. This emerging technology aims to create three-dimensional functional scaffolds by accurately depositing layer-by-layer bio-inks composed of biomaterial and cells. As a novel bio-ink, a decellularized extracellular matrix can serve as an appropriate substrate that contains all the necessary biological cues for cellular interactions. Here, this review is intended to provide an overview of decellularized extracellular matrix-based bio-inks and their properties, sources, and preparation process. Following this, decellularized extracellular matrix-based bio-inks for cartilage tissue engineering are discussed, emphasizing cell behavior and in-vivo applications. Afterward, the current challenges and future outlook will be discussed to determine the conclusing remarks.

    Changning Sun, Jianfeng Kang, Chuncheng Yang, Jibao Zheng, Yanwen Su, Enchun Dong, Yingjie Liu, Siqi Yao, Changquan Shi, Huanhao Pang, Jiankang He, Ling Wang, Chaozong Liu, Jianhua Peng, Liang Liu, Yong Jiang, Dichen Li
    2022, 3(2):  116-133.  doi:10.12336/biomatertransl.2022.02.001
    Polyether-ether-ketone (PEEK) is a candidate material for the manufacture of next-generation orthopaedic implants. Customised PEEK implants have been used in clinical applications with the development of additive manufacturing. The design, manufacturing, evaluation and typical applications of PEEK customised implants are comprehensively reviewed.
    Abstract ( 693 )   HTML ( 48)   PDF (5186KB) ( 1202 )  
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    Polyether-ether-ketone (PEEK) is believed to be the next-generation biomedical material for orthopaedic implants that may replace metal materials because of its good biocompatibility, appropriate mechanical properties and radiolucency. Currently, some PEEK implants have been used successfully for many years. However, there is no customised PEEK orthopaedic implant made by additive manufacturing licensed for the market, although clinical trials have been increasingly reported. In this review article, design criteria, including geometric matching, functional restoration, strength safety, early fixation, long-term stability and manufacturing capability, are summarised, focusing on the clinical requirements. An integrated framework of design and manufacturing processes to create customised PEEK implants is presented, and several typical clinical applications such as cranioplasty patches, rib prostheses, mandibular prostheses, scapula prostheses and femoral prostheses are described. The main technical challenge faced by PEEK orthopaedic implants lies in the poor bonding with bone and soft tissue due to its biological inertness, which may be solved by adding bioactive fillers and manufacturing porous architecture. The lack of technical standards is also one of the major factors preventing additive-manufactured customised PEEK orthopaedic implants from clinical translation, and it is good to see that the abundance of standards in the field of additive-manufactured medical devices is helping them enter the clinical market.

    Feifei Pu, Wei Wu, Doudou Jing, Yihan Yu, Yizhong Peng, Jianxiang Liu, Qiang Wu, Baichuan Wang, Zhicai Zhang, Zengwu Shao
    2022, 3(2):  134-141.  doi:10.12336/biomatertransl.2022.02.005
    Three-dimensional (3D)-printed prostheses with an individualised design can achieve satisfactory shortterm clinical efficacy in the reconstruction of large bone defects after bone tumour resection. Using this method it is possible to print complex structures that 
    are difficult to fabricate using traditional processes, and overcome the problems of stress shielding and low biological activity of conventional prostheses.
    Abstract ( 216 )   HTML ( 21)   PDF (1878KB) ( 420 )  
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    Reconstruction after resection has always been an urgent problem in the treatment of bone tumours. There are many methods that can be used to reconstruct bone defects; however, there are also many complications, and it is difficult to develop a safe and effective reconstruction plan for the treatment of bone tumours. With the rapid development of digital orthopaedics, three-dimensional printing technology can solve this problem. The three-dimensional printing of personalised prostheses has many advantages. It can be used to print complex structures that are difficult to fabricate using traditional processes and overcome the problems of stress shielding and low biological activity of conventional prostheses. In this study, 12 patients with bone tumours were selected as research subjects, and based on individualised reverse-engineering design technology, a three-dimensional model of each prosthesis was designed and installed using medical image data. Ti6Al4V was used as the raw material to prepare the prostheses, which were used to repair bone defects after surgical resection. The operation time was 266.43 ± 21.08 minutes (range 180–390 minutes), and intraoperative blood loss was 857.26 ± 84.28 mL (range 800–2500 mL). One patient had delayed wound healing after surgery, but all patients survived without local tumour recurrence, and no tumour metastasis was found. No aseptic loosening or structural fracture of the prosthesis, and no non-mechanical prosthesis failure caused by infection, tumour recurrence, or progression was observed. The Musculo-Skeletal Tumour Society (MSTS) score of limb function was 22.53 ± 2.09 (range 16–26), and ten of the 12 patients scored ≥ 20 and were able to function normally. The results showed that three-dimensional printed prostheses with an individualised design can achieve satisfactory short-term clinical efficacy in the reconstruction of large bone defects after bone tumour resection.

    Seyed Ataollah Naghavi, Changning Sun, Mahbubeh Hejazi, Maryam Tamaddon, Jibao Zheng, Leilei Wang, Chenrui Zhang, Swastina Nath Varma, Dichen Li, Mehran Moazen, Ling Wang, Chaozong Liu
    2022, 3(2):  142-151.  doi:10.12336/biomatertransl.2022.02.006
    Polyether-ether-ketone is an excellent biomaterial that has potential in orthopaedic applications. Additive Manufacturing has been widely used in fabrication of customer-tailored implants such as skull, spinal cage, rib cage, and scaffold for large bone defect reconstructions. The achieved mechanical performance of the implants is a key factor for translation of additive manufacturing. In this study, the compression, tension, three-point bending and torsion specimens were designed and additive manufacturing manufactured. The mechanical properties were tested and compared with the computational results.
    Abstract ( 388 )   HTML ( 26)   PDF (3062KB) ( 480 )  
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    Polyether-ether-ketone (PEEK) is widely used in producing prosthesis and have gained great attention for repair of large bone defect in recent years with the development of additive manufacturing. This is due to its excellent biocompatibility, good heat and chemical stability and similar mechanical properties which mimics natural bone. In this study, three replicates of rectilinear scaffolds were designed for compression, tension, three-point bending and torsion test with unit cell size of 0.8 mm, a pore size of 0.4 mm, strut thickness of 0.4 mm and nominal porosity of 50%. Stress-strain graphs were developed from experimental and finite element analysis models. Experimental Young’s modulus and yield strength of the scaffolds were measured from the slop of the stress-strain graph to be 395 and 19.50 MPa respectively for compression, 427 and 6.96 MPa respectively for tension, 257 and 25.30 MPa respectively for three-point bending and 231 and 12.83 MPa respectively for torsion test. The finite element model was found to be in good agreement with the experimental results. Ductile fracture of the struct subjected to tensile strain was the main failure mode of the PEEK scaffold, which stems from the low crystallinity of additive manufacturing PEEK. The mechanical properties of porous PEEK are close to those of cancellous bone and thus are expected to be used in additive manufacturing PEEK bone implants in the future, but the lower yield strength poses a design challenge.

    Panita Maturavongsadit, Weiwei Wu, Jingyu Fan, Igor B. Roninson, Taixing Cui, Qian Wang
    2022, 3(2):  152-161.  doi:10.12336/biomatertransl.2022.02.007
    This study demonstrates a novel biodegradable graphene-incorporated hyaluronic acid-based hydrogel that can effectively accommodate and deliver the cyclin-dependent kinase 8/19 inhibitor Senexin A to the adventitia of vessel grafts without any observed toxicity in vitro. The versatility of this hydrogel system supports its potential translation as a perivascular drug delivery system for treating occlusive vascular diseases.
    Abstract ( 304 )   HTML ( 12)   PDF (1110KB) ( 427 )  
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    Perivascular delivery of therapeutic agents against established aetiologies for occlusive vascular remodelling has great therapeutic potential for vein graft failure. However, none of the perivascular drug delivery systems tested experimentally have been translated into clinical practice. In this study, we established a novel strategy to locally and sustainably deliver the cyclin-dependent kinase 8/19 inhibitor Senexin A (SenA), an emerging drug candidate to treat occlusive vascular disease, using graphene oxide-hybridised hyaluronic acid-based hydrogels. We demonstrated an approach to accommodate SenA in hyaluronic acid-based hydrogels through utilising graphene oxide nanosheets allowing for non-covalent interaction with SenA. The resulting hydrogels produced sustained delivery of SenA over 21 days with tunable release kinetics. In vitro assays also demonstrated that the hydrogels were biocompatible. This novel graphene oxide-incorporated hyaluronic acid hydrogel offers an optimistic outlook as a perivascular drug delivery system for treating occlusive vascular diseases, such as vein graft failure.

    Hui Li, Peng Yang, JiHyeon Hwang, Parasmani Pageni, Alan W. Decho, Chuanbing Tang
    2022, 3(2):  162-171.  doi:10.12336/biomatertransl.2022.02.008
    Metallopolymer double-network (DN) hydrogels, composed of a first network of cationic cobaltocenium polyelectrolytes and a second network of polyacrylamide, are fabricated via two-step free radical polymerization. After installation with antibiotics, the hydrogel conjugates show remarkable mechanical ability, antifouling and antimicrobial properties.
    Abstract ( 588 )   HTML ( 24)   PDF (1498KB) ( 562 )  
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    Compared with single-network hydrogels, double-network hydrogels offer higher mechanical strength and toughness. Integrating useful functions into double-network hydrogels can expand the portfolios of the hydrogels. We report the preparation of double-network metallopolymer hydrogels with remarkable hydration, antifouling, and antimicrobial properties. These cationic hydrogels are composed of a first network of cationic cobaltocenium polyelectrolytes and a second network of polyacrylamide, all prepared via radical polymerization. Antibiotics were further installed into the hydrogels via ion-complexation with metal cations. These hydrogels exhibited significantly enhanced hydration, compared with polyacrylamide-based hydrogels, while featuring robust mechanical strength. Cationic metallopolymer hydrogels exhibited strong antifouling against oppositely charged proteins. These antibiotic-loaded hydrogels demonstrated a synergistic effect on the inhibition of bacterial growth and antifouling of bacteria, as a result of the unique ion complexation of cobaltocenium cations.