Key considerations on the development of biodegradable biomaterials for clinical translation of medical devices: With cartilage repair products as an example.

With the interdisciplinary convergence of biology, medicine and materials science, both research and clinical translation of biomaterials are progressing at a rapid pace. However, there is still a huge gap between applied basic research on biomaterials and their translational products - medical devices, where two significantly different perspectives and mindsets often work independently and non-synergistically, which in turn significantly increases financial costs and research effort. Although this gap is well-known and often criticized in the biopharmaceutical industry, it is gradually widening. In this article, we critically examine the developmental pipeline of biodegradable biomaterials and biomaterial-based medical device products. Then based on clinical needs, market analysis, and relevant regulations, some ideas are proposed to integrate the two different mindsets to guide applied basic research and translation of biomaterial-based products, from the material and technical perspectives. Cartilage repair substitutes are discussed here as an example. Hopefully, this will lay a strong foundation for biomaterial research and clinical translation, while reducing the amount of extra research effort and funding required due to the dissonance between innovative basic research and commercialization pipeline.

3D-printed scaffolds with synergistic effect of hollow-pipe structure and bioactive ions for vascularized bone regeneration.

Segmental bone regeneration remains a considerable challenge due to the associated low degree of vascularization. To solve this problem, in this study, hollow-pipe-packed silicate bioceramic (BRT-H) scaffolds are fabricated using a coaxial three-dimensional (3D) printing technique. Based on a modified core/shell printer nozzle and a modulated viscoelastic bioceramic paste, hollow struts with an external diameter of 1 mm and internal dimeter of 500 µm can be directly printed, yielding a compressive strength of the BRT-H scaffolds as high as 26 MPa. Apart from the effects on osteogenesis, the bioactive ions released from the BRT scaffolds can also facilitate angiogenesis via inducing endothelial cell migration. More importantly, the hollow pipes not only significantly promote the rapid infiltration of host blood vessels into the channels but also exhibit great advantages for the delivery of stem cells and growth factors to further enhance tissue regeneration. When used for the regeneration of rabbit radius segmental defects, radiological and histological findings indicate that the BRT-H scaffolds can enhance early vascularization and later bone regeneration and remodeling. Taken together, the hollow pipes and the ionic products from BRT-H scaffolds have a synergistic effect on enhancing vascularized bone regeneration.

[Experimental study on long-term prevention effect of chitosan electrospun membrane on cerebrospinal fluid leakage].

OBJECTIVE: To study the long-term prevention effect of self-developed chitosan electrospun membrane on cerebrospinal fluid leakage. METHODS: Twenty-five healthy adult New Zealand rabbits were selected to prepare the bilateral dural defect (0.8 cem x 0.8 cm in size) via midline incision of head. Defect of the right was repaired with chitosan electrospun membrane as the experimental group; defect of the left was not repaired as the control group. At 2-16 weeks after operation, one rabbit was sacrificed for the general observation of inflammatory response surrounding bone window and absorption of chitosan electrospun membrane; at 3 and 6 weeks after operation, 5 rabbits were sacrificed for sampling to observe histological change and collagen expression by_HE and Masson staining, and to measure the expressions of epidermal growth factor receptor (EGFR) and basic fibroblast growth factor (bFGF) by immunohistochemical staining. RESULTS: No inflammatory reaction of swelling, exudation, and sppuration appeared in the skin and subcutaneous tissue after operation in 2 groups. There was no adhesion around the chitosan electrospun membrane, and new fiber membrane formed under the chitosan electrospun membrane in the experimental group; no cerebrospinal fluid leakage happened; the chitosan electrospun membrane was gradually degraded with time, and was completely absorbed at 16 weeks. There was uneven scar around the dural detect in control group. Histological observation showed less inflammatory cell infiltration in the experimental group, showing significant difference in the number of inflammatory cells compared with control group at 3, 6 weeks (P < 0.05); capillary, granulation tissue and collagen fiber massively proliferated; collagen fiber arranged in line, and there was a clear borderline between chitosan electrospurn membrane and adjacent collagen fiber. The immunohistochemical staining showed that there were high expressions of bFGF and EGFR in the experimental group, and low expressions of bFGF and EGFR in the control group. CONCLUSION: Chitosan electrospun membrane for dural defect of rabbit can effectively reconstruct the dura, and it has exact long-term prevention effect on cerebrospinal fluid leakage.

Preparation, mechanical property and cytocompatibility of poly(L-lactic acid)/calcium silicate nanocomposites with controllable distribution of calcium silicate nanowires.

How to accurately control the microstructure of bioactive inorganic/organic nanocomposites still remains a significant challenge, which is of great importance in influencing their mechanical strength and biological properties. In this study, using a combined method of electrospinning and hot press processing, calcium silicate hydrate (CSH) nanowire/poly(L-lactide) (PLLA) nanocomposites with controllable microstructures and tailored mechanical properties were successfully prepared as potential bone graft substitutes. The electrospun hybrid nanofibers with various degrees of alignment were stacked together in a predetermined manner and hot pressed into hierarchically structured nanocomposites. The relationship between the microstructure and mechanical properties of the as-prepared nanocomposites were systematically evaluated. The results showed that CSH nanowires in a PLLA matrix were able to be controlled from completely randomly oriented to uniaxially aligned, and then hierarchically organized with different interlayer angles, leading to corresponding nanocomposites with improved mechanical properties and varied anisotropies. It was also found that the bending strength of nanocomposites with 5 wt.% CSH nanowires (130 MPa) was significantly higher than that of pure PLLA (86 MPa) and other composites. The addition of CSH nanowires greatly enhanced the hydrophilicity and apatite-forming ability of PLLA films, as well as the attachment and proliferation of bone marrow stromal cells. The study suggested that a combination of electrospinning and hot pressing is a viable means to control the microstructure and mechanical properties, and improve the mineralization ability and cellular responses, of CSH/PLLA nanocomposites for potential bone repair applications.

Hierarchically structured nanocrystalline hydroxyapatite assembled hollow fibers as a promising protein delivery system.

Nanocrystalline hydroxyapatite assembled hollow fibers (NHAHF) in the membrane form were fabricated by combining the electrospinning technique and the hydrothermal method. This novel hierarchical tubular structure of hydroxyapatite exhibited excellent protein loading capacity and long-term sustained release property.

Polymer nanocomposites with controllable distribution and arrangement of inorganic nanocomponents.

A novel approach to prepare nanocomposites encapsulating one or multiple kinds of nanoelements with diverse spatial distribution patterns and orientational organization manners was reported. Nanowires were uniaxially aligned over macroscopic dimensions within bulk composites, which recreated the basic structural hierarchy of bone and displayed comparable excellent mechanical properties.