Innovative biomaterials, drugs and technologies for musculoskeletal diseases

Musculoskeletal diseases are challenging medical conditions in the world with increasing prevalence, which bring heavy burden to the patients, families, and healthcare system of our society. Considering that many musculoskeletal disorders lack effective diagnostic or recovery methods, it is essential to explore novel strategies for these diseases. In this issue, we have included publications on the latest advances on innovative biomaterials, pharmaceutical molecules, and technologies for some of challenging musculoskeletal diseases, as well as animal models established for exploring the underlying mechanisms of those approaches.

Although bone tissue has self-repair ability, effective bone repair is needed since it usually takes months for the spontaneous bone repair. In addition, further efforts are often required in many circumstances including critical-sized bone defects, delayed bone union, tumor, etc., and biomaterials have been proven to effectively facilitate bone repair. Recently, tissue-engineered periosteum showed extensive potential for osteogenesis. Zhang et al. summarized the significance of periosteum for osteogenesis and chondrogenesis from the aspects of periosteum tissue structure, osteogenesis performance, clinical application, development of periosteum tissue engineering, as well as the pros and cons of different tissue engineering methods [1]. The titanium (Ti) and CoCrMo alloys have been extensively used as prostheses in patients with massive bone defects or amputation. However, these materials can only provide mechanical support and lack the ability to promote bone regeneration. Guo et al. improved the prostheses by utilizing the carbon fibre-reinforced polyetheretherketone (PEEK) material combining with TiCu/TiCuN and found that it promoted bone repair through angiogenesis [2]. Likewise, silicon-substituted calcium phosphate (Si-CaP) ceramic promoted angiogenesis and bone apposition in the defect site. Therefore, Cui et al. combined Si-CaP with autogenous fine particulate bone powder, which alleviated spinal fusion with bone marrow-derived stem cells in a rabbit model [3]. As magnesium (Mg) has good biodegradability, biocompatibility and osteogenic stimulation ability, Zhu et al. enhanced angiogenesis with Mg implants to alleviate the development of medication-related osteonecrosis of the jaw [4]. Zhang et al. built porous Mg scaffolds using 3D gel-printing method, and the scaffolds were coated with dibasic calcium phosphate dihydrate to further improve biocompatibility and bone regeneration ability [5]. Another material source for bone repair is xenografts. To improve the biofunctionality of grafts with accurate regulation, Xu et al. constructed a novel xenograft bovine bone scaffold named (DSS)6-liposome/CKIP-1 siRNA/calcine bone, which inhibited CKIP-1 expression, promoted osteoblast proliferation, and improved osteogenesis in rats [6].

Unlike bone, mature articular cartilage lacks self-repair ability. Hence, biomaterials play a much more important role in improving cartilage regeneration. However, collagen and hyaluronic acid, the main components of cartilage extracellular matrix (ECM), have limited cell affinity to mesenchymal stem cells or chondrocytes. Inspired by mussel, Gan et al. developed a native cartilage ECM-mimicking scaffold with polydopamine to enhance cell adhesion and differentiation, while improving the immune microenvironment at the same time [7]. Differently, Liao et al. addressed this problem by directly embedding adipose-derived stem cells into alginate microspheres, with gelatin promoting cell adhesion and proliferation [8]. Yuan et al. enhanced the biofunctionality and immunomodulation ability of PEEK scaffolds by sulfonation modification [9]. Since the mechanical strength is critical for weight-bearing tissues, and inappropriate mechanical properties could lead to cartilage degeneration, the researchers adjusted the compressive modulus of sulfonated PEEK by fabricating porous scaffold using 3D printing technology [9]. Based on a similar rationale, Yang et al. fabricated a stiff subchondral bony compartment using 3D printing to constantly provide mechanical support for long-term cartilage regeneration [10]. Similar approaches have also been applied to intervertebral disc (IVD). In order to prevent IVD degeneration, Jia et al. developed a hydrogel with injectability, high bio-safety, and nucleus pulposus-matched viscoelastic property [11]. Meniscus is another load bearing cartilaginous tissue in the synovial joint of knee. To facilitate meniscus regeneration, Yan et al. transplanted a mixed natural material composed of particulated juvenile allograft cartilage and synovium, which resulted in superior structural integrity, superficial smoothness, and marginal integration [12]. In this way, the microenvironment of the repair site can be regulated locally, as synovium and synoviocytes play a vital role in the knee joint including nutrition supplement and inflammatory response. In line with this, Cao et al. characterized an osteoarthritis subtype by synovial lipid metabolism disorder and fibroblast-like synoviocyte dysfunction [13].

The advanced computational and robotic technologies such as 3D printing can not only fabricate scaffolds, but also help building up customized devices for scientific research. Li et al. constructed a movable unloading device by 3D printing to help establishing the disuse osteoporosis mouse model [14]. In clinic, the robotic-assisted total knee arthroplasty (TKA) system has been introduced to practice, offering more accurate operations with reduced bone resection extent and soft tissue damage. Xia et al. evaluated the accuracy of a newly designed “Skywalker” robot for TKA in 31 patients in Shanghai, China [15]; Li et al. evaluated the new robotic system named HURWA in a prospective randomized and multicenter study [16], both resulting in safe, effective, and better alignment for mechanical axis compared to conventional TKA. The computational technology can also help clinicians on disease diagnosis. Liu et al. developed an automatic phantom-less quantitative computed tomography system that significantly improved the accuracy and precision to measure spinal bone mineral density and diagnose osteoporosis [17].

Apart from the biomaterials and high-tech devices, Chinese medicine is a large field which remains under-explored, partially because the components from herbs usually bring mild adverse effects. Therefore, the effect and mechanistic study of Chinese medicine is one of the rising directions in basic and translational research, with the Nobel Prize drug artemisinin as an example. Qiu et al. found that puerarin, a component isolated from the root of the Puerariae lobate Ohwi, was able to disrupt osteoclast activation via blocking integrin-β3 Pyk2/Src/Cbl signaling pathway [18]. Zhang et al. found that baicalein, a flavonoid compound derived from the root of Scutellaria baicalensis, mediated the anti-tumor activity in osteosarcoma through lncRNA-NEF driven Wnt/β-catenin signaling regulatory axis [19]. These chemical explorations provide promising candidates to drug and biomaterial development.

We anticipate that this issue will provide researchers and clinicians valuable insight into the challenges that the musculoskeletal diseases pose, as well as novel strategies to investigate and treat these diseases.