IUPAC-PSK50

Presenter(s)

ERIC XIAO (Beijing Maybio-pharmaceutical Biotech Development Co., Ltd.)

Co-Author(s)

No co-authors

Abstract

I. Research Background and Clinical Pain Points in Maxillofacial Repair

In the fields of oral and maxillofacial surgery, craniomaxillofacial trauma reconstruction, and plastic surgery, maxillofacial soft tissue defects and volumetric collapse triggered by severe trauma, congenital deformities (such as micrognathia and mandibular retrusion), tumor resections, and degenerative diseases have long stood as highly challenging medical dilemmas. Due to the intricate anatomical structures of the maxillofacial region, replacement materials are subject to exceptionally stringent requirements regarding bioactivity, physical mechanical support strength, 3D space-maintaining capability, and long-term tissue histocompatibility.
Currently, the mainstream clinical decellularized extracellular matrix (ECM) materials predominantly rely on animal tissue extraction or human cadaveric donation. In maxillofacial repair applications, these two traditional technological pathways reveal severe, irreversible bottlenecks: animal-derived ECM retains residual heterologous antigens, carrying potential immunogenic risks, and harsh decellularization extraction processes cause a massive loss of vital bioactive components, making it difficult to effectively induce the "active regeneration" of complex maxillofacial tissues. Conversely, cadaveric human ECM, while exhibiting better biocompatibility, heavily depends on scarce cadaver donations, leading to profound ethical, compliance, and legal liabilities within the raw material supply chain; furthermore, extreme donor batch-to-batch variations make it entirely incapable of supporting the clinical demands of standardized, industrial-scale mass production.
To conquer the aforementioned bottlenecks, this study drives a paradigm shift from "passive tissue extraction" to "synthetic biology customization" by pioneering a first-in-class, "gene-enhanced" induced pluripotent stem cell-derived human extracellular matrix (iPS-ECM) technology platform. Through active engineering and composition optimization, this platform creates a 100% animal-free, cadaver-free, and virus-free cyto-engineered human ECM, securing a disruptive global technological high ground for maxillofacial volumetric repair and functional tissue regeneration.

II. Technical Principles and Cyto-Engineering Customization Methods

The core of this research lies in establishing clinical-grade Human Col-CiPS seed cells, actively modifying and regulating the composition and functionality of iPS cells through precise gene-editing tools at the raw material source.
Gene Enhancement and Targeted Regulation: This strategy addresses the critical technical checkpoints of directing iPS cell differentiation into induced mesenchymal stem cells (iMSCs) and engineered induced fibroblast (iFbs) working cells. Through gene-editing technologies, the expression systems of core structural proteins within the ECM are actively regulated to stimulate high-volume secretion of a regenerative-enhanced human extracellular matrix in vitro, thereby resolving the shortcomings of low bioactivity and poor compatibility seen in conventional materials.
3D Scalable Bio-Manufacturing: The team developed proprietary cell culture media and porous polymer carriers with nanostructures for standardized, large-scale 3D cell culture inside bioreactors. Utilizing gentle and efficient purification processes, cellular components are entirely eradicated while a high-density collagen and non-collagenous matrix protein network remains fully preserved.
Maxillofacial Scaffold Formulation: To meet the specialized space-maintenance and mechanical loading demands of the maxillofacial region, the purified cyto-engineered human ECM is formulated into high-strength "cross-linked scaffolds" and "soluble micronized matrix-type gels," successfully crossing the threshold of commercial mass production at low manufacturing costs.

III. Experimental Results and Validation in Maxillofacial Regenerative Application

Molecular Validation of Gene-Enhanced Clones: Flow cytometry characterization verified that the differentiated iMSC seed cells were highly pure, with strong positive expression rates for markers CD90, CD73, and CD105 reaching 99.8%, 96.2%, and 99.7%, respectively. PCR and alignment against NCBI genomic libraries confirmed that the target gene expression levels achieved a breakthrough jump: the relative expression of the core collagen component COL1A1 increased by approximately 10-fold, and COL1A2 rose by 15- to 20-fold, with highly controllable co-expression of COL2A1. This provides a highly bioactive molecular matrix for high-efficiency maxillofacial soft tissue repair and reconstruction.
Microstructural and Composition Analysis: Scanning electron microscopy (SEM) and protein mass spectrometry confirmed that the purified cyto-engineered human ECM closely mimicked the human native dermal ECM microenvironment in its 3D micro-scaffold architecture. The structural network retained a complete profile of non-collagenous matrix proteins (such as FN1, POSTN, FBN1, VCAN, LAMB1), with a total protein content as high as 75%–90%, demonstrating supreme cellular adhesion and proliferation-promoting abilities.
Clinical Translation Trials for Mandibular Retrusion: Leveraging this bio-synthetic engineering platform, the team successfully developed an "injectable extracellular matrix collagen gel" (Code: MB-005) designated for Class III medical device classification to treat soft tissue volumetric deficiencies like mandibular retrusion. The product displays outstanding rapid reconstitution dispersibility, film-forming capability, and strong volumetric structural support for structural restoration.
Clinical Outcomes: To date, clinical trial enrollment has been successfully completed for over 190 patients. Multi-center trials led by clinical experts at Peking Union Medical College Hospital, Peking University Third Hospital, and Sun Yat-sen Memorial Hospital demonstrated superior volume retention and immediate aesthetic contouring at 1-month and 3-month post-injection follow-ups. Ultrasound and radiographic imaging confirmed excellent host tissue integration, zero severe immunogenic rejection, a negligible complication rate, and an exceptional capacity for long-term in vivo tissue-inductive regeneration.

IV. Conclusion

The "gene-enhanced" iPS-ECM platform developed in this study successfully shatters the supply chain bottlenecks and safety boundaries associated with cadaveric tissues and animal-derived heterologous antigens in maxillofacial repair. It represents the world's first industrial-scale mass production of a native-like, customizable human extracellular matrix at a production cost comparable to bacterial fermentation.
In maxillofacial regenerative medicine, this biomaterial outperforms traditional products across both technical benchmarks (including purity, ultra-low DNA residue, and endotoxin metrics) and clinical regenerative performance in 190 mandibular retrusion cases. With a completed 10,000 ㎡integrated research facility and GMP manufacturing plant in Hunan, Maybio is positioned to advance Class III medical device registrations and iterate further maxillofacial applications, including vocal cord paralysis matrix fiber (MB-034) and cartilage repair (MB-035). This technology offers a standardized "Chinese Solution" to global regenerative medicine, realizing a revolutionary paradigm shift from "passive structural filling" to "active induced regeneration".

I. Research Background and Clinical Pain Points in Maxillofacial Repair

In the fields of oral and maxillofacial surgery, craniomaxillofacial trauma reconstruction, and plastic surgery, maxillofacial soft tissue defects and volumetric collapse triggered by severe trauma, congenital deformities (such as micrognathia and mandibular retrusion), tumor resections, and degenerative diseases have long stood as highly challenging medical dilemmas. Due to the intricate anatomical structures of the maxillofacial region, replacement materials are subject to exceptionally stringent requirements regarding bioactivity, physical mechanical support strength, 3D space-maintaining capability, and long-term tissue histocompatibility.
Currently, the mainstream clinical decellularized extracellular matrix (ECM) materials predominantly rely on animal tissue extraction or human cadaveric donation. In maxillofacial repair applications, these two traditional technological pathways reveal severe, irreversible bottlenecks: animal-derived ECM retains residual heterologous antigens, carrying potential immunogenic risks, and harsh decellularization extraction processes cause a massive loss of vital bioactive components, making it difficult to effectively induce the "active regeneration" of complex maxillofacial tissues. Conversely, cadaveric human ECM, while exhibiting better biocompatibility, heavily depends on scarce cadaver donations, leading to profound ethical, compliance, and legal liabilities within the raw material supply chain; furthermore, extreme donor batch-to-batch variations make it entirely incapable of supporting the clinical demands of standardized, industrial-scale mass production.
To conquer the aforementioned bottlenecks, this study drives a paradigm shift from "passive tissue extraction" to "synthetic biology customization" by pioneering a first-in-class, "gene-enhanced" induced pluripotent stem cell-derived human extracellular matrix (iPS-ECM) technology platform. Through active engineering and composition optimization, this platform creates a 100% animal-free, cadaver-free, and virus-free cyto-engineered human ECM, securing a disruptive global technological high ground for maxillofacial volumetric repair and functional tissue regeneration.

II. Technical Principles and Cyto-Engineering Customization Methods

The core of this research lies in establishing clinical-grade Human Col-CiPS seed cells, actively modifying and regulating the composition and functionality of iPS cells through precise gene-editing tools at the raw material source.
Gene Enhancement and Targeted Regulation: This strategy addresses the critical technical checkpoints of directing iPS cell differentiation into induced mesenchymal stem cells (iMSCs) and engineered induced fibroblast (iFbs) working cells. Through gene-editing technologies, the expression systems of core structural proteins within the ECM are actively regulated to stimulate high-volume secretion of a regenerative-enhanced human extracellular matrix in vitro, thereby resolving the shortcomings of low bioactivity and poor compatibility seen in conventional materials.
3D Scalable Bio-Manufacturing: The team developed proprietary cell culture media and porous polymer carriers with nanostructures for standardized, large-scale 3D cell culture inside bioreactors. Utilizing gentle and efficient purification processes, cellular components are entirely eradicated while a high-density collagen and non-collagenous matrix protein network remains fully preserved.
Maxillofacial Scaffold Formulation: To meet the specialized space-maintenance and mechanical loading demands of the maxillofacial region, the purified cyto-engineered human ECM is formulated into high-strength "cross-linked scaffolds" and "soluble micronized matrix-type gels," successfully crossing the threshold of commercial mass production at low manufacturing costs.

III. Experimental Results and Validation in Maxillofacial Regenerative Application

Molecular Validation of Gene-Enhanced Clones: Flow cytometry characterization verified that the differentiated iMSC seed cells were highly pure, with strong positive expression rates for markers CD90, CD73, and CD105 reaching 99.8%, 96.2%, and 99.7%, respectively. PCR and alignment against NCBI genomic libraries confirmed that the target gene expression levels achieved a breakthrough jump: the relative expression of the core collagen component COL1A1 increased by approximately 10-fold, and COL1A2 rose by 15- to 20-fold, with highly controllable co-expression of COL2A1. This provides a highly bioactive molecular matrix for high-efficiency maxillofacial soft tissue repair and reconstruction.
Microstructural and Composition Analysis: Scanning electron microscopy (SEM) and protein mass spectrometry confirmed that the purified cyto-engineered human ECM closely mimicked the human native dermal ECM microenvironment in its 3D micro-scaffold architecture. The structural network retained a complete profile of non-collagenous matrix proteins (such as FN1, POSTN, FBN1, VCAN, LAMB1), with a total protein content as high as 75%–90%, demonstrating supreme cellular adhesion and proliferation-promoting abilities.
Clinical Translation Trials for Mandibular Retrusion: Leveraging this bio-synthetic engineering platform, the team successfully developed an "injectable extracellular matrix collagen gel" (Code: MB-005) designated for Class III medical device classification to treat soft tissue volumetric deficiencies like mandibular retrusion. The product displays outstanding rapid reconstitution dispersibility, film-forming capability, and strong volumetric structural support for structural restoration.
Clinical Outcomes: To date, clinical trial enrollment has been successfully completed for over 190 patients. Multi-center trials led by clinical experts at Peking Union Medical College Hospital, Peking University Third Hospital, and Sun Yat-sen Memorial Hospital demonstrated superior volume retention and immediate aesthetic contouring at 1-month and 3-month post-injection follow-ups. Ultrasound and radiographic imaging confirmed excellent host tissue integration, zero severe immunogenic rejection, a negligible complication rate, and an exceptional capacity for long-term in vivo tissue-inductive regeneration.

IV. Conclusion

The "gene-enhanced" iPS-ECM platform developed in this study successfully shatters the supply chain bottlenecks and safety boundaries associated with cadaveric tissues and animal-derived heterologous antigens in maxillofacial repair. It represents the world's first industrial-scale mass production of a native-like, customizable human extracellular matrix at a production cost comparable to bacterial fermentation.
In maxillofacial regenerative medicine, this biomaterial outperforms traditional products across both technical benchmarks (including purity, ultra-low DNA residue, and endotoxin metrics) and clinical regenerative performance in 190 mandibular retrusion cases. With a completed 10,000 ㎡integrated research facility and GMP manufacturing plant in Hunan, Maybio is positioned to advance Class III medical device registrations and iterate further maxillofacial applications, including vocal cord paralysis matrix fiber (MB-034) and cartilage repair (MB-035). This technology offers a standardized "Chinese Solution" to global regenerative medicine, realizing a revolutionary paradigm shift from "passive structural filling" to "active induced regeneration".