Nankai University & Shanghai Ninth People's Hospital Unveil Novel Cell-Laden Micro-Nano Composite Fibrous Scaffold for Regenerative Medicine
On July 9, Nankai University and Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, jointly disclosed a patent for bio-regenerative materials.
This patent discloses a cell-laden micro/nano composite fibrous structural material, which addresses current limitations in the design of bio-regenerative materials—such as low cell loading efficiency, compromised cell viability, and impaired functional performance—thereby enabling more effective application in the fabrication of medical devices for tissue repair.
Modifying Material Structure to Achieve Cellular Loading
As a critical therapeutic approach for tissue defects, tissue engineering can restore the original function, morphology, and mechanical properties of tissues. In this context, cell transplantation can enhance therapeutic efficacy, while biomaterials serve as cell carriers to provide a biomimetic microenvironment, thereby improving cell loading efficiency and retention rate, and enhancing cellular activity and function.
However, current scaffold materials, such as 3D-printed scaffolds, hydrogels, and fibrous membranes, are commonly used to load cells to promote anisotropic tissue regeneration. Although 3D printing inks like collagen and gelatin can support cell loading, their mechanical strength is weak, making them difficult to use for the repair of load-bearing tissues such as the Achilles tendon. Furthermore, hydrogels are limited by their poor mechanical properties, low strength, and lack of biomimetic guidance structures, which restricts tissue regeneration and integration.
To address this critical challenge, the team led by Zhu Meifeng at Nankai University and the team led by Zhou Guangdong at Shanghai Ninth People’s Hospital jointly developed a cell-laden micro-nano composite fibrous scaffold material, featuring three key innovations:
First, the nanofibers of this material provide physical topographical cues that guide cell migration and spreading, direct the oriented deposition of extracellular matrix, promote macrophage polarization, and regulate the immune microenvironment;
Secondly, its microfibers provide mechanical support; the large pore sizes between the microfibers can alleviate the excessive density of the nanofiber structure, improve cell infiltration, promote revascularization, and maintain mechanical strength.
Finally, this material features a microporous outer shell that prevents infiltration by surrounding tissues and cells, thereby avoiding adhesions and scarring during tissue regeneration while ensuring the transport of nutrients.
By conducting in vivo cell survival experiments with micro-nano composite fibrous structural materials, the team observed significant retention markers of cells within rats over a 14-day period, demonstrating that cell viability was enhanced when cells were loaded onto these micro-nano composite fibrous structural materials.。
Multiple Clinical Applications, Over 100 Products Approved
Bioregenerative materials represent a sector within regenerative medicine characterized by rapid clinical progress, strong commercial certainty, and a clear pathway for the translation of technological achievements.Currently, more than 100 regenerative medical devices and drug-device combination products have been approved. Furthermore, in terms of clinical application, the use of bio-regenerative materials in orthopedics, trauma repair, and medical aesthetics is becoming increasingly mature.。
Among these applications, bone defect repair is the most common and widespread scenario for bio-regenerative materials. Currently, 74 domestically produced products based on bio-regenerative materials have received approval from the National Medical Products Administration (NMPA), of which 58 are indicated for bone defect repair in non-weight-bearing sites.
Notably, bone repair materials incorporating active factors have garnered significant attention. Currently, only four BMP-2–enhanced bone repair materials have received regulatory approval in China: Jiuyuan Gene’s bone repair material, Zhenghai Biotechnology’s Active Biological Bone, Ruibang Biotechnology’s self-setting calcium phosphate artificial bone, and Medtronic’s bone repair material. These products stimulate DNA synthesis and cellular replication, thereby promoting the directed differentiation of mesenchymal cells into osteoblasts. When loaded onto bone repair materials, they effectively facilitate fractured bone regeneration.
In the field of trauma repair, according to statistics from VCBeat Research Institute, a total of 84 domestically produced trauma repair materials have received approval from the National Medical Products Administration (NMPA). The trauma repair sector encompasses numerous subfields, categorized by application scenarios. For instance, Zhenghai Biotechnology has launched the Haifu Skin Repair Membrane for tissue-engineered skin, which can effectively repair burn wounds and improve healing quality. It also promotes the healing of soft tissues on organ surfaces, where it is replaced by newly formed soft tissue while undergoing biodegradation. Additionally, in the area of peripheral nerve repair, Tianxinfu has introduced artificial nerve conduits to facilitate the restoration of the peripheral nervous system.
In the field of medical aesthetics, “Sculptra” and “Ellansé” are currently the star products in regenerative aesthetics. The core component of “Sculptra” is poly-L-lactic acid (PLLA), which activates fibroblasts to stimulate the production of collagen and elastic fibers, thereby providing structural support to the skin and achieving a brighter, more radiant complexion. “Ellansé,” on the other hand, is composed of 30% polycaprolactone (PCL) and 70% carboxymethyl cellulose (CMC).
Currently, there are four “youth-restoring injections” and “girl-like needle” products approved for marketing in China: Sinocare’s Aivlan, Imeik’s Ru Bai Angel, Huadong Medicine’s Ellansé, and Jiangsu Wuzhong’s AestheFill.
Materials Are Becoming Increasingly Composite
The clinical application of bio-regenerative materials is continuously deepening, with increasingly diverse product forms. These materials have undergone a significant transformation from natural to synthetic, from single-component to composite materials, and from basic to high-end applications.
Among these, composite materials are composed of elements with distinct chemical and mechanical properties. Unlike single-phase materials with homogeneous structures, they can more accurately replicate the function of damaged bodily tissues. For instance, composites formed from polylactic acid (PLA) and calcium phosphate ceramics utilize the alkalinity of the calcium phosphate ceramics to neutralize the acidity of PLA degradation products, while also promoting bone tissue healing to a certain extent. In China, numerous bioregenerative material companies and research institutions are actively investing in research and development, continuously launching innovative products.
In 2015, a team led by Xue Zhen at the Second Affiliated Hospital of Harbin Medical University developed an injectable composite material composed of nano-hydroxyapatite, chitosan, and calcium sulfate hemihydrate by mimicking biological principles. Implantation studies in rabbit muscle demonstrated that the material was essentially fully degraded within eight weeks post-implantation, eliciting only a mild inflammatory response during the process, thereby exhibiting excellent degradability.
In 2022, Allgens Medical also developed a new generation of polyester/mineralized collagen composite artificial bone repair material. By incorporating biodegradable polyester materials into the mineralized collagen system, the company created this next-generation artificial bone repair material. Using an animal model of cancellous bone defects in the femoral condyles of rabbits, it was demonstrated that the new material exhibits excellent biocompatibility and osteogenic activity, with significantly improved mechanical properties in the regenerated bone tissue.