New concepts in biologics are discussed in the latest JBJS Specialty Update, What’s New in Biologics. Here, we spotlight the 5 most compelling studies, as selected by lead author Constance R. Chu, MD.
What Is a Biologic?
Orthobiologics, or biologic approaches for enhancing tissue regeneration within the musculoskeletal system, extend far beyond platelet-rich plasma and minimally manipulated bone marrow- or adipose tissue-derived products. While these first-generation approaches still dominate current discussion, attention should be directed toward advancing the future1.
Many Current Orthobiologic Treatments Are Considered Unproven
To improve evidence-based practice, recommendations from a National Institutes of Health work group on improving clinical trials addressing a common orthobiologic goal of joint preservation in knee osteoarthritis (OA) were published. The group stressed the importance of defining the targeted mechanisms of action and therapeutic goals in preclinical and clinical trials that evaluate the efficacy of a biologic2.
A Potential Role for Allogenic Products
The clinical outcomes of allogenic mesenchymal stem cell (MSC) therapy for knee OA were evaluated in a narrative review of the literature. Adipose tissue was the most common source across 11 analyzed studies. The injections were safe, provided durable pain reduction, and improved symptom scores3.
Optimization of Autologous Products
A study of human adipose-derived MSCs found that senescence during culture expansion inhibited the therapeutic efficacy of the MSCs for musculoskeletal regeneration. However, fisetin, a senolytic agent, reduced markers of senescence while maintaining the differentiation potential of the expanded MSCs4.
Engineering Cells to Maximize Therapeutic Benefit
Circadian rhythms influence biologic processes, including when therapeutic needs are greatest. In a proof-of-concept study, a “chronogenetic” gene circuit was engineered that could express specific genes on a timed program based on the intrinsic clock circuits of the cells. The circuits were shown to peak reliably at specific circadian times across multiple days5.
What’s New in Biologics is freely available at JBJS.org.
What’s New by Subspecialty
Each month, JBJS publishes a review of the most pertinent studies from the orthopaedic literature in a select subspecialty. To read the reports, visit the What’s New by Subspecialty collection at JBJS.org.
Recent OrthoBuzz posts include: What’s New in Hand and Wrist Surgery, What’s New in Machine Learning and Generative AI, and What’s New in Pediatric Orthopaedics.
References
- Costa FR, Pires L, Martins RA, Santos M, Santos GS, Lana JV, Costa BR, Santos N, de Macedo AP, Kruel A, Lana JF. Orthobiologics revisited: a concise perspective on regenerative orthopedics. Curr Issues Mol Biol. 2025 Apr 2;47(4):247.
- Chu CR, Hochberg M, White D, Rodeo S, Huard J, Shapiro S, Lattermann C, Guilak F. Transformative approaches for effective clinical trials to reduce the disease burden of osteoarthritis. Semin Arthritis Rheum. 2025 Apr;71:152652.
- Johnson S, Boettcher BJ, Korpershoek JV, Hevesi M, Saris DBF, Nagelli CV. Allogeneic mesenchymal stromal cell injections for knee osteoarthritis: a review of clinical outcomes. Regen Med. 2025 Oct;20(10):501-7.
- Mullen M, Nelson AL, Goff A, Billings J, Kloser H, Huard C, Mitchell J, Hambright WS, Ravuri S, Huard J. Fisetin attenuates cellular senescence accumulation during culture expansion of human adipose-derived stem cells. Stem Cells. 2023 Jul 14;41(7):698-710.
- Cimino A, Pat F, Oyebamiji O, Pferdehirt L, Pham CTN, Herzog ED, Guilak F. Programmable chronogenetic gene circuits for self-regulated circadian delivery of biologic drugs. J Control Release. 2025 Sep 10;385:113959.